Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200015 (University of Belgrade, Institute for Medical Research)

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Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200015 (University of Belgrade, Institute for Medical Research) (en)
Ministarstvo prosvete, nauke i tehnološkog razvoja Republike Srbije, Ugovor br. 451-03-68/2020-14/200015 (Univerzitet u Beogradu, Institut za medicinska istraživanja) (sr_RS)
Министарство просвете, науке и технолошког развоја Републике Србије, Уговор бр. 451-03-68/2020-14/200015 (Универзитет у Београду, Институт за медицинска истраживања) (sr)
Authors

Publications

Polyphenol-rich black currant and cornelian cherry juices ameliorate metabolic syndrome induced by a high-fat high-fructose diet in Wistar rats

Paunović, Marija; Milošević, Maja; Mitrović-Ajtić, Olivera; Veličković, Nataša; Micić, Bojana; Nedić, Olgica; Todorović, Vanja; Vučić, Vesna; Petrović, Snježana

(Elsevier Ltd, 2024)

TY  - JOUR
AU  - Paunović, Marija
AU  - Milošević, Maja
AU  - Mitrović-Ajtić, Olivera
AU  - Veličković, Nataša
AU  - Micić, Bojana
AU  - Nedić, Olgica
AU  - Todorović, Vanja
AU  - Vučić, Vesna
AU  - Petrović, Snježana
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5598
AB  - Diets high in fat and sugar lead to metabolic syndrome (MetS) and related chronic diseases. We investigated the effects of commercially available, cold-pressed polyphenol-rich black currant (BC) and cornelian cherry (CC) juices on the prevention of MetS in Wistar rats induced by a 10-weeks high-fat high-fructose (HFF) diet. Juice consumption, either BC or CC, with a HFF diet resulted in lower serum triglycerides compared to only the HFF consumption. Both juices also mitigated the effects of HFF on the liver, pancreas, and adipose tissue, by preserving liver and pancreas histomorphology and reducing visceral fat and adipocyte size. Furthermore, supplementation with both juices reduced glucagon and up-regulated insulin expression in the pancreas of the rats on the HFF diet, whereas the BC also showed improved glucose regulation. BC juice also reduced the expression of IL-6 and hepatic inflammation compared to the group only on HFF diet. Both juices, especially BC, could be a convenient solution for the prevention of MetS in humans.
PB  - Elsevier Ltd
T2  - Heliyon
T1  - Polyphenol-rich black currant and cornelian cherry juices ameliorate metabolic syndrome induced by a high-fat high-fructose diet in Wistar rats
VL  - 10
IS  - 7
DO  - 10.1016/j.heliyon.2024.e27709
ER  - 
@article{
author = "Paunović, Marija and Milošević, Maja and Mitrović-Ajtić, Olivera and Veličković, Nataša and Micić, Bojana and Nedić, Olgica and Todorović, Vanja and Vučić, Vesna and Petrović, Snježana",
year = "2024",
abstract = "Diets high in fat and sugar lead to metabolic syndrome (MetS) and related chronic diseases. We investigated the effects of commercially available, cold-pressed polyphenol-rich black currant (BC) and cornelian cherry (CC) juices on the prevention of MetS in Wistar rats induced by a 10-weeks high-fat high-fructose (HFF) diet. Juice consumption, either BC or CC, with a HFF diet resulted in lower serum triglycerides compared to only the HFF consumption. Both juices also mitigated the effects of HFF on the liver, pancreas, and adipose tissue, by preserving liver and pancreas histomorphology and reducing visceral fat and adipocyte size. Furthermore, supplementation with both juices reduced glucagon and up-regulated insulin expression in the pancreas of the rats on the HFF diet, whereas the BC also showed improved glucose regulation. BC juice also reduced the expression of IL-6 and hepatic inflammation compared to the group only on HFF diet. Both juices, especially BC, could be a convenient solution for the prevention of MetS in humans.",
publisher = "Elsevier Ltd",
journal = "Heliyon",
title = "Polyphenol-rich black currant and cornelian cherry juices ameliorate metabolic syndrome induced by a high-fat high-fructose diet in Wistar rats",
volume = "10",
number = "7",
doi = "10.1016/j.heliyon.2024.e27709"
}
Paunović, M., Milošević, M., Mitrović-Ajtić, O., Veličković, N., Micić, B., Nedić, O., Todorović, V., Vučić, V.,& Petrović, S.. (2024). Polyphenol-rich black currant and cornelian cherry juices ameliorate metabolic syndrome induced by a high-fat high-fructose diet in Wistar rats. in Heliyon
Elsevier Ltd., 10(7).
https://doi.org/10.1016/j.heliyon.2024.e27709
Paunović M, Milošević M, Mitrović-Ajtić O, Veličković N, Micić B, Nedić O, Todorović V, Vučić V, Petrović S. Polyphenol-rich black currant and cornelian cherry juices ameliorate metabolic syndrome induced by a high-fat high-fructose diet in Wistar rats. in Heliyon. 2024;10(7).
doi:10.1016/j.heliyon.2024.e27709 .
Paunović, Marija, Milošević, Maja, Mitrović-Ajtić, Olivera, Veličković, Nataša, Micić, Bojana, Nedić, Olgica, Todorović, Vanja, Vučić, Vesna, Petrović, Snježana, "Polyphenol-rich black currant and cornelian cherry juices ameliorate metabolic syndrome induced by a high-fat high-fructose diet in Wistar rats" in Heliyon, 10, no. 7 (2024),
https://doi.org/10.1016/j.heliyon.2024.e27709 . .

Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats

Paunović, Marija; Kotur-Stevuljević, Jelena; Arsić, Aleksandra; Milošević, Maja; Todorović, Vanja; Guzonjić, Azra; Vučić, Vesna; Petrović, Snježana

(MDPI, 2023)

TY  - JOUR
AU  - Paunović, Marija
AU  - Kotur-Stevuljević, Jelena
AU  - Arsić, Aleksandra
AU  - Milošević, Maja
AU  - Todorović, Vanja
AU  - Guzonjić, Azra
AU  - Vučić, Vesna
AU  - Petrović, Snježana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4918
AB  - A Western-style diet, rich in fat and simple sugars, is the main risk factor for a significant number of chronic diseases and disorders, as well as for a progression of metabolic syndrome (MetS). One of the key mechanisms involved in MetS development is increased oxidative stress caused by the accumulation of body fat. Some dietary polyphenols have shown a protective role in preventing oxidative-stress-induced damage. We investigated the difference in the oxidative response of plasma, liver, and visceral adipose tissue in rats fed with a high-fat high-fructose (HFF) diet for ten weeks, and the effectiveness of polyphenol-rich juices (black currant (BC) and cornelian cherry (CC)) in HFF-diet-induced oxidative stress prevention. The most prominent impact of the HFF diet on redox parameters was recorded in the liver, whereas adipose tissue showed the most potent protection mechanisms against oxidative stress. Consumption of both juices decreased advanced oxidation protein product (AOPP) level in plasma, increased paraoxonase1 (PON1) activity in the liver, and significantly decreased total oxidative status (TOS) in adipose tissue. BC exerted stronger antioxidative potential than CC and decreased the superoxide anion radical (O2•−) level in the liver. It also reduced TOS, total antioxidative status (TAS), and malondialdehyde (MDA) concentration in adipose tissue. The multiple linear regression analysis has shown that the best predictors of MetS development, estimated through the increase in visceral adiposity, were superoxide dismutase (SOD), AOPP, TOS, and TAS. The consumption of polyphenol-rich juices may provide a convenient approach for the systemic reduction of oxidative stress parameters.
PB  - MDPI
T2  - Antioxidants
T1  - Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats
VL  - 12
IS  - 6
DO  - 10.3390/antiox12061148
ER  - 
@article{
author = "Paunović, Marija and Kotur-Stevuljević, Jelena and Arsić, Aleksandra and Milošević, Maja and Todorović, Vanja and Guzonjić, Azra and Vučić, Vesna and Petrović, Snježana",
year = "2023",
abstract = "A Western-style diet, rich in fat and simple sugars, is the main risk factor for a significant number of chronic diseases and disorders, as well as for a progression of metabolic syndrome (MetS). One of the key mechanisms involved in MetS development is increased oxidative stress caused by the accumulation of body fat. Some dietary polyphenols have shown a protective role in preventing oxidative-stress-induced damage. We investigated the difference in the oxidative response of plasma, liver, and visceral adipose tissue in rats fed with a high-fat high-fructose (HFF) diet for ten weeks, and the effectiveness of polyphenol-rich juices (black currant (BC) and cornelian cherry (CC)) in HFF-diet-induced oxidative stress prevention. The most prominent impact of the HFF diet on redox parameters was recorded in the liver, whereas adipose tissue showed the most potent protection mechanisms against oxidative stress. Consumption of both juices decreased advanced oxidation protein product (AOPP) level in plasma, increased paraoxonase1 (PON1) activity in the liver, and significantly decreased total oxidative status (TOS) in adipose tissue. BC exerted stronger antioxidative potential than CC and decreased the superoxide anion radical (O2•−) level in the liver. It also reduced TOS, total antioxidative status (TAS), and malondialdehyde (MDA) concentration in adipose tissue. The multiple linear regression analysis has shown that the best predictors of MetS development, estimated through the increase in visceral adiposity, were superoxide dismutase (SOD), AOPP, TOS, and TAS. The consumption of polyphenol-rich juices may provide a convenient approach for the systemic reduction of oxidative stress parameters.",
publisher = "MDPI",
journal = "Antioxidants",
title = "Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats",
volume = "12",
number = "6",
doi = "10.3390/antiox12061148"
}
Paunović, M., Kotur-Stevuljević, J., Arsić, A., Milošević, M., Todorović, V., Guzonjić, A., Vučić, V.,& Petrović, S.. (2023). Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats. in Antioxidants
MDPI., 12(6).
https://doi.org/10.3390/antiox12061148
Paunović M, Kotur-Stevuljević J, Arsić A, Milošević M, Todorović V, Guzonjić A, Vučić V, Petrović S. Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats. in Antioxidants. 2023;12(6).
doi:10.3390/antiox12061148 .
Paunović, Marija, Kotur-Stevuljević, Jelena, Arsić, Aleksandra, Milošević, Maja, Todorović, Vanja, Guzonjić, Azra, Vučić, Vesna, Petrović, Snježana, "Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats" in Antioxidants, 12, no. 6 (2023),
https://doi.org/10.3390/antiox12061148 . .
1

Erythrocyte fatty acid aberrations in amyotrophic lateral sclerosis – correlation with disease duration

Minić, Rajna; Arsić, Aleksandra; Kojadinović, Milica; Palibrk, Aleksa; Đorđević, Brižita; Stević, Zorica

(Society of Medical Biochemists of Serbia, 2023)

TY  - JOUR
AU  - Minić, Rajna
AU  - Arsić, Aleksandra
AU  - Kojadinović, Milica
AU  - Palibrk, Aleksa
AU  - Đorđević, Brižita
AU  - Stević, Zorica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5301
AB  - Background: Recent literature data highlights metabolic changes in amyotrophic lateral sclerosis (ALS). To explore possible early metabolic changes, we aimed to analyse the fatty acids (FA) composition of erythrocytes in newly diagnosed ALS patients and to see whether fatty acid levels correlate with the ALSFRS-R score or disease duration. Methods: The severity of motor function involvement was assessed by the ALSFRS-R scale at the initial evaluation. The fatty acid profile of erythrocyte membranes was analysed by gas-liquid chromatography. The study comprised 26 clinically diagnosed ALS patients, with mean ALSFRS-R 38±8. The control group included 26 healthy volunteers. Results: Significantly higher levels of palmitic acid and total saturated FAs were detected in ALS patients. In ALS patients, total monounsaturated FA, palmitoleic, vaccenic, and oleic acid were also significantly increased. The levels of eicosapentaenoic acid, docosapentaenoic acid, total polyunsaturated FA (PUFA) and n-6 PUFA were significantly lower in ALS patients. Additionally, a-linolenic acid, the precursor of the n-3 PUFA family, was not detected in ALS patients. We found no significant correlation between the ALSFRS-R score and the abundance of individual FAs analysed. A moderate negative correlation was found between disease duration and DHA level, and a positive correlation was detected with MUFA. Conclusion: Experimental evidence presented may contribute to shaping a beneficial nutritional intervention.
AB  - Uvod: Dostupni literaturni podaci ističu značaj metaboličkih promena kod amiotrofične lateralne skleroze (ALS). Sa ciljem da istražimo moguće rane metaboličke promene analizirali smo sastav masnih kiselina (MK) eritrocita kod novodijagnostikovanih ALS pacijenata da bi videli da li nivoi masnih kiselina koreliraju sa ALSFRS-R ocenom ili trajanjem bolesti. Metode: Stepen oštećenja motoričke funkcije procenjivan je ALSFRS-R skalom pri početnoj proceni. Studija je obuhvatila 26 klinički dijagnostikovanih ALS pacijenata, srednja vrednost ALSFRS-R bila je 38±8. Kontrolnu grupu činilo je 26 zdravih dobrovoljaca. Profil masnih kiselina membrana eritrocita je analiziran gasno-tečnom hromatografijom. Rezultati: Značajno viši nivoi palmitinske kiseline i ukupnih zasićenih MK nađeni su kod ALS pacijenata. Ukupne mono nezasićene MK, palmitoleinska, vakcenska i oleinska kiselina takođe su bile značajno povećane kod ALS pacijenata. Nivoi eikozapentaenske kiseline, dokozapentaenske kiseline, ukupne polinezasićene MK (PUFA) i n-6 PUFA bili su značajno niži kod pacijenata sa ALS. Pored toga, a- linolenska kiselina, prekursor porodice n-3 PUFA, uopšte nije detektovana kod ALS pacijenata. Nismo prona{li zna- ~ajnu korelaciju izme|u ALSFRS-R ocene i nivoa pojedinačnih analiziranih MK. Umerena negativna korelacija je prona|ena između trajanja bolesti i nivoa DHA, a nađena je pozitivna korelacija trajanja bolesti sa nivoom MUFA. Zaključak: Prikazani eksperimentalni dokazi mogu doprineti oblikovanju korisne nutritivne intervencije.
PB  - Society of Medical Biochemists of Serbia
T2  - Journal of Medical Biochemistry
T1  - Erythrocyte fatty acid aberrations in amyotrophic lateral sclerosis – correlation with disease duration
T1  - Izmenjen profil masnih kiselina eritrocita pacijenata sa amiotrofičnom lateralnom sklerozom – korelacija sa trajanjem bolesti
VL  - 42
IS  - 4
SP  - 621
EP  - 629
DO  - 10.5937/jomb0-40387
ER  - 
@article{
author = "Minić, Rajna and Arsić, Aleksandra and Kojadinović, Milica and Palibrk, Aleksa and Đorđević, Brižita and Stević, Zorica",
year = "2023",
abstract = "Background: Recent literature data highlights metabolic changes in amyotrophic lateral sclerosis (ALS). To explore possible early metabolic changes, we aimed to analyse the fatty acids (FA) composition of erythrocytes in newly diagnosed ALS patients and to see whether fatty acid levels correlate with the ALSFRS-R score or disease duration. Methods: The severity of motor function involvement was assessed by the ALSFRS-R scale at the initial evaluation. The fatty acid profile of erythrocyte membranes was analysed by gas-liquid chromatography. The study comprised 26 clinically diagnosed ALS patients, with mean ALSFRS-R 38±8. The control group included 26 healthy volunteers. Results: Significantly higher levels of palmitic acid and total saturated FAs were detected in ALS patients. In ALS patients, total monounsaturated FA, palmitoleic, vaccenic, and oleic acid were also significantly increased. The levels of eicosapentaenoic acid, docosapentaenoic acid, total polyunsaturated FA (PUFA) and n-6 PUFA were significantly lower in ALS patients. Additionally, a-linolenic acid, the precursor of the n-3 PUFA family, was not detected in ALS patients. We found no significant correlation between the ALSFRS-R score and the abundance of individual FAs analysed. A moderate negative correlation was found between disease duration and DHA level, and a positive correlation was detected with MUFA. Conclusion: Experimental evidence presented may contribute to shaping a beneficial nutritional intervention., Uvod: Dostupni literaturni podaci ističu značaj metaboličkih promena kod amiotrofične lateralne skleroze (ALS). Sa ciljem da istražimo moguće rane metaboličke promene analizirali smo sastav masnih kiselina (MK) eritrocita kod novodijagnostikovanih ALS pacijenata da bi videli da li nivoi masnih kiselina koreliraju sa ALSFRS-R ocenom ili trajanjem bolesti. Metode: Stepen oštećenja motoričke funkcije procenjivan je ALSFRS-R skalom pri početnoj proceni. Studija je obuhvatila 26 klinički dijagnostikovanih ALS pacijenata, srednja vrednost ALSFRS-R bila je 38±8. Kontrolnu grupu činilo je 26 zdravih dobrovoljaca. Profil masnih kiselina membrana eritrocita je analiziran gasno-tečnom hromatografijom. Rezultati: Značajno viši nivoi palmitinske kiseline i ukupnih zasićenih MK nađeni su kod ALS pacijenata. Ukupne mono nezasićene MK, palmitoleinska, vakcenska i oleinska kiselina takođe su bile značajno povećane kod ALS pacijenata. Nivoi eikozapentaenske kiseline, dokozapentaenske kiseline, ukupne polinezasićene MK (PUFA) i n-6 PUFA bili su značajno niži kod pacijenata sa ALS. Pored toga, a- linolenska kiselina, prekursor porodice n-3 PUFA, uopšte nije detektovana kod ALS pacijenata. Nismo prona{li zna- ~ajnu korelaciju izme|u ALSFRS-R ocene i nivoa pojedinačnih analiziranih MK. Umerena negativna korelacija je prona|ena između trajanja bolesti i nivoa DHA, a nađena je pozitivna korelacija trajanja bolesti sa nivoom MUFA. Zaključak: Prikazani eksperimentalni dokazi mogu doprineti oblikovanju korisne nutritivne intervencije.",
publisher = "Society of Medical Biochemists of Serbia",
journal = "Journal of Medical Biochemistry",
title = "Erythrocyte fatty acid aberrations in amyotrophic lateral sclerosis – correlation with disease duration, Izmenjen profil masnih kiselina eritrocita pacijenata sa amiotrofičnom lateralnom sklerozom – korelacija sa trajanjem bolesti",
volume = "42",
number = "4",
pages = "621-629",
doi = "10.5937/jomb0-40387"
}
Minić, R., Arsić, A., Kojadinović, M., Palibrk, A., Đorđević, B.,& Stević, Z.. (2023). Erythrocyte fatty acid aberrations in amyotrophic lateral sclerosis – correlation with disease duration. in Journal of Medical Biochemistry
Society of Medical Biochemists of Serbia., 42(4), 621-629.
https://doi.org/10.5937/jomb0-40387
Minić R, Arsić A, Kojadinović M, Palibrk A, Đorđević B, Stević Z. Erythrocyte fatty acid aberrations in amyotrophic lateral sclerosis – correlation with disease duration. in Journal of Medical Biochemistry. 2023;42(4):621-629.
doi:10.5937/jomb0-40387 .
Minić, Rajna, Arsić, Aleksandra, Kojadinović, Milica, Palibrk, Aleksa, Đorđević, Brižita, Stević, Zorica, "Erythrocyte fatty acid aberrations in amyotrophic lateral sclerosis – correlation with disease duration" in Journal of Medical Biochemistry, 42, no. 4 (2023):621-629,
https://doi.org/10.5937/jomb0-40387 . .

Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause

Bokan, Goran; Glamočanin, Tanja; Mavija, Zoran; Vidović, Bojana; Stojanović, Ana; Björnsson, Einar; Vučić, Vesna

(MDPI, 2023)

TY  - JOUR
AU  - Bokan, Goran
AU  - Glamočanin, Tanja
AU  - Mavija, Zoran
AU  - Vidović, Bojana
AU  - Stojanović, Ana
AU  - Björnsson, Einar
AU  - Vučić, Vesna
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4997
AB  - Herb-induced liver injury (HILI) caused by herbal supplements, natural products, and products used in traditional medicine are important for differential diagnoses in patients with acute liver injury without an obvious etiology. The root of Withania somnifera (L.) Dunal, commonly known as ashwagandha, has been used in Ayurvedic medicine for thousands of years to promote health and longevity. Due to various biological activities, ashwagandha and its extracts became widespread as herbal supplements on the global market. Although it is generally considered safe, there are several reported cases of ashwagandha-related liver injury, and one case ended with liver transplantation. In this paper, we review all reported cases so far. Additionally, we describe two new cases of ashwagandha hepatotoxicity. In the first case, a 36-year-old man used ashwagandha capsules (450 mg, three times daily) for 6 months before he developed nausea, pruritus, and dark-colored urine. In the second case, a 30-year-old woman developed pruritus after 45 days of using ashwagandha capsules (450 mg). In both cases, serum bilirubin and liver enzymes (aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were increased. The liver injury pattern was hepatocellular (R-value 11.1) and mixed (R-value 2.6), respectively. The updated Roussel Uclaf Causality Assessment Method (RUCAM) (both cases with a score of seven) indicated a “probable” relationship with ashwagandha. Clinical and liver function improvements were observed after the discontinuation of ashwagandha supplement use. By increasing the data related to ashwagandha-induced liver injury, these reports support that consuming ashwagandha supplements is not without its safety concerns.
PB  - MDPI
T2  - Pharmaceuticals
T1  - Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause
VL  - 16
IS  - 8
DO  - 10.3390/ph16081129
ER  - 
@article{
author = "Bokan, Goran and Glamočanin, Tanja and Mavija, Zoran and Vidović, Bojana and Stojanović, Ana and Björnsson, Einar and Vučić, Vesna",
year = "2023",
abstract = "Herb-induced liver injury (HILI) caused by herbal supplements, natural products, and products used in traditional medicine are important for differential diagnoses in patients with acute liver injury without an obvious etiology. The root of Withania somnifera (L.) Dunal, commonly known as ashwagandha, has been used in Ayurvedic medicine for thousands of years to promote health and longevity. Due to various biological activities, ashwagandha and its extracts became widespread as herbal supplements on the global market. Although it is generally considered safe, there are several reported cases of ashwagandha-related liver injury, and one case ended with liver transplantation. In this paper, we review all reported cases so far. Additionally, we describe two new cases of ashwagandha hepatotoxicity. In the first case, a 36-year-old man used ashwagandha capsules (450 mg, three times daily) for 6 months before he developed nausea, pruritus, and dark-colored urine. In the second case, a 30-year-old woman developed pruritus after 45 days of using ashwagandha capsules (450 mg). In both cases, serum bilirubin and liver enzymes (aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were increased. The liver injury pattern was hepatocellular (R-value 11.1) and mixed (R-value 2.6), respectively. The updated Roussel Uclaf Causality Assessment Method (RUCAM) (both cases with a score of seven) indicated a “probable” relationship with ashwagandha. Clinical and liver function improvements were observed after the discontinuation of ashwagandha supplement use. By increasing the data related to ashwagandha-induced liver injury, these reports support that consuming ashwagandha supplements is not without its safety concerns.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause",
volume = "16",
number = "8",
doi = "10.3390/ph16081129"
}
Bokan, G., Glamočanin, T., Mavija, Z., Vidović, B., Stojanović, A., Björnsson, E.,& Vučić, V.. (2023). Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause. in Pharmaceuticals
MDPI., 16(8).
https://doi.org/10.3390/ph16081129
Bokan G, Glamočanin T, Mavija Z, Vidović B, Stojanović A, Björnsson E, Vučić V. Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause. in Pharmaceuticals. 2023;16(8).
doi:10.3390/ph16081129 .
Bokan, Goran, Glamočanin, Tanja, Mavija, Zoran, Vidović, Bojana, Stojanović, Ana, Björnsson, Einar, Vučić, Vesna, "Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause" in Pharmaceuticals, 16, no. 8 (2023),
https://doi.org/10.3390/ph16081129 . .
3
1

Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films

Kurćubić, Ivana; Đuriš, Jelena; Cvijić, Sandra; Crevar, Milkica; Ibrić, Svetlana; Miloradović, Zoran; Mihailović-Stanojević, Nevena; Karanović, Danijela; Ivanov, Milan; Jovović, Đurđica; Vajić, Una-Jovana

(Elsevier, 2023)

TY  - JOUR
AU  - Kurćubić, Ivana
AU  - Đuriš, Jelena
AU  - Cvijić, Sandra
AU  - Crevar, Milkica
AU  - Ibrić, Svetlana
AU  - Miloradović, Zoran
AU  - Mihailović-Stanojević, Nevena
AU  - Karanović, Danijela
AU  - Ivanov, Milan
AU  - Jovović, Đurđica
AU  - Vajić, Una-Jovana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4932
AB  - In order to exploit the advantage of drug delivery through the buccal mucosa, mucoadhesive buccal films with propranolol hydrochloride based on polyethylene oxide, hydroxypropyl methylcellulose, and polyvinyl alcohol have been developed. The aim of this study was the development, pharmaceutical-technological (uniformity of mass and drug content, film thickness, potential interactions between polymers and propranolol hydrochloride, in vitro drug permeation and drug release, mechanical and mucoadhesive properties), and biopharmaceutical characterization of prepared mucoadhesive buccal films through conducting in vivo study in spontaneously hypertensive rats and in silico modeling of intraoral and gastrointestinal drug absorption. For in vivo study formulation F2 (hydroxypropylmethyl cellulose 0.5%, polyethylene oxide 3.5%, polyvinyl alcohol 1.5%, propylene glycol 3%, and propranolol hydrochloride 2%) was selected, which showed the highest values of tensile strength and percentage of elongation, as well as the highest value of the force of adhesion. Results of pharmacokinetic in rats and in silico modeling confirmed the superiority of the mucoadhesive buccal films over immediate-release tablets (in rats: AUC0→24h 66.13 ± 18.03 vs. 24.61 ± 5.52 μg⋅h/mL, AUC0→∞ 111.82 ± 39.04 vs. 47.85 ± 11.67 μg⋅h/mL; in silico: AUC0→24h 200.17 vs.74.58 ng⋅h/mL, AUC0→∞ 204.04 vs. 75.64 ng⋅h/mL). Hemodynamic measurements have shown that mucoadhesive buccal films, compared to immediate-release tablets, provide a more pronounced decrease primarily in heart rate (28-51%), but also in diastolic pressure (up to 33%), as well as a longer heart rate reduction that was maintained for up to 12th h. Therefore, mucoadhesive buccal films increased the degree of absorbed drug and thus contributed to better therapeutic outcomes compared to immediate-release tablets for peroral administration.
PB  - Elsevier
T2  - Journal of Drug Delivery Science and Technology
T1  - Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films
VL  - 86
DO  - 10.1016/j.jddst.2023.104715
ER  - 
@article{
author = "Kurćubić, Ivana and Đuriš, Jelena and Cvijić, Sandra and Crevar, Milkica and Ibrić, Svetlana and Miloradović, Zoran and Mihailović-Stanojević, Nevena and Karanović, Danijela and Ivanov, Milan and Jovović, Đurđica and Vajić, Una-Jovana",
year = "2023",
abstract = "In order to exploit the advantage of drug delivery through the buccal mucosa, mucoadhesive buccal films with propranolol hydrochloride based on polyethylene oxide, hydroxypropyl methylcellulose, and polyvinyl alcohol have been developed. The aim of this study was the development, pharmaceutical-technological (uniformity of mass and drug content, film thickness, potential interactions between polymers and propranolol hydrochloride, in vitro drug permeation and drug release, mechanical and mucoadhesive properties), and biopharmaceutical characterization of prepared mucoadhesive buccal films through conducting in vivo study in spontaneously hypertensive rats and in silico modeling of intraoral and gastrointestinal drug absorption. For in vivo study formulation F2 (hydroxypropylmethyl cellulose 0.5%, polyethylene oxide 3.5%, polyvinyl alcohol 1.5%, propylene glycol 3%, and propranolol hydrochloride 2%) was selected, which showed the highest values of tensile strength and percentage of elongation, as well as the highest value of the force of adhesion. Results of pharmacokinetic in rats and in silico modeling confirmed the superiority of the mucoadhesive buccal films over immediate-release tablets (in rats: AUC0→24h 66.13 ± 18.03 vs. 24.61 ± 5.52 μg⋅h/mL, AUC0→∞ 111.82 ± 39.04 vs. 47.85 ± 11.67 μg⋅h/mL; in silico: AUC0→24h 200.17 vs.74.58 ng⋅h/mL, AUC0→∞ 204.04 vs. 75.64 ng⋅h/mL). Hemodynamic measurements have shown that mucoadhesive buccal films, compared to immediate-release tablets, provide a more pronounced decrease primarily in heart rate (28-51%), but also in diastolic pressure (up to 33%), as well as a longer heart rate reduction that was maintained for up to 12th h. Therefore, mucoadhesive buccal films increased the degree of absorbed drug and thus contributed to better therapeutic outcomes compared to immediate-release tablets for peroral administration.",
publisher = "Elsevier",
journal = "Journal of Drug Delivery Science and Technology",
title = "Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films",
volume = "86",
doi = "10.1016/j.jddst.2023.104715"
}
Kurćubić, I., Đuriš, J., Cvijić, S., Crevar, M., Ibrić, S., Miloradović, Z., Mihailović-Stanojević, N., Karanović, D., Ivanov, M., Jovović, Đ.,& Vajić, U.. (2023). Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films. in Journal of Drug Delivery Science and Technology
Elsevier., 86.
https://doi.org/10.1016/j.jddst.2023.104715
Kurćubić I, Đuriš J, Cvijić S, Crevar M, Ibrić S, Miloradović Z, Mihailović-Stanojević N, Karanović D, Ivanov M, Jovović Đ, Vajić U. Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films. in Journal of Drug Delivery Science and Technology. 2023;86.
doi:10.1016/j.jddst.2023.104715 .
Kurćubić, Ivana, Đuriš, Jelena, Cvijić, Sandra, Crevar, Milkica, Ibrić, Svetlana, Miloradović, Zoran, Mihailović-Stanojević, Nevena, Karanović, Danijela, Ivanov, Milan, Jovović, Đurđica, Vajić, Una-Jovana, "Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films" in Journal of Drug Delivery Science and Technology, 86 (2023),
https://doi.org/10.1016/j.jddst.2023.104715 . .
1
1

Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes

Jaćević, Vesna; Dumanović, Jelena; Grujić-Milanović, Jelica; Milovanović, Zoran; Amidžić, Ljiljana; Vojinović, Nataša; Nežić, Lana; Marković, Bojan; Dobričić, Vladimir; Milosavljević, Petar; Nepovimova, Eugenie; Kuča, Kamil

(Elsevier B.V., 2023)


                                            

                                            
Jaćević, V., Dumanović, J., Grujić-Milanović, J., Milovanović, Z., Amidžić, L., Vojinović, N., Nežić, L., Marković, B., Dobričić, V., Milosavljević, P., Nepovimova, E.,& Kuča, K.. (2023). Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes. in Chemico-biological interactions
Elsevier B.V.., 383, 110658.
https://doi.org/10.1016/j.cbi.2023.110658
Jaćević V, Dumanović J, Grujić-Milanović J, Milovanović Z, Amidžić L, Vojinović N, Nežić L, Marković B, Dobričić V, Milosavljević P, Nepovimova E, Kuča K. Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes. in Chemico-biological interactions. 2023;383:110658.
doi:10.1016/j.cbi.2023.110658 .
Jaćević, Vesna, Dumanović, Jelena, Grujić-Milanović, Jelica, Milovanović, Zoran, Amidžić, Ljiljana, Vojinović, Nataša, Nežić, Lana, Marković, Bojan, Dobričić, Vladimir, Milosavljević, Petar, Nepovimova, Eugenie, Kuča, Kamil, "Oxidative stress status assessment of rats' brains injury following subacute exposure to K-oximes" in Chemico-biological interactions, 383 (2023):110658,
https://doi.org/10.1016/j.cbi.2023.110658 . .

Selectivity of polyclonal repertoire of anti-microbial IgA and its subclasses in saliva and serum in humans

Nikodijević, Slavomir; Blagojević, Veljko; Ćuruvija, Ivana; Kosanović, Dejana; Đukić, Tamara; Đorđević, Brižita; Ilić, Vesna; Minić, Rajna

(John Wiley and Sons Inc, 2022)

TY  - JOUR
AU  - Nikodijević, Slavomir
AU  - Blagojević, Veljko
AU  - Ćuruvija, Ivana
AU  - Kosanović, Dejana
AU  - Đukić, Tamara
AU  - Đorđević, Brižita
AU  - Ilić, Vesna
AU  - Minić, Rajna
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4294
AB  - Increased interest in microbiota calls for the thorough analysis of antibody reactivity to different microorganisms. As salivary IgA represents the first line of defence against microorganisms contacting mucosal surfaces, we explored the binding and specificity of salivary IgA by testing the binding of purified, FITC-labelled salivary IgA to different microorganisms in flow cytometry and conclude that this kind of analysis enables the differentiation of species/strains with high IgA binding capacity, which should be corroborated on a larger sample size. Further we compare, with in-house ELISA, the binding of polyclonal salivary IgA with the binding of polyclonal serum IgA from the same individuals to whole microbial cells and to purified microbial components. High correlations were obtained in total salivary IgA binding to Lactobacillus rhamnosus and Escherichia coli, very distant bacterial species, as well as to isolated bacterial components (r =.70–.97). The binding of total salivary IgA resembled the binding of both salivary IgA1 and IgA2, with IgA2 predominating. For serum polyclonal IgA repertoire, substantially higher specificity was obtained. Serum IgA binding to E. coli correlated best with serum IgA binding to lipopolysaccharide (r =.86), and serum IgA against L. rhamnosus correlated best with the anti-peptidoglycan IgA levels (r =.88). We have also detected that total serum IgA response is governed by either IgA1 or IgA2 response, depending on the nature of the antigen/s. We conclude that steady state salivary IgA repertoire, unlike serum IgA repertoire, consists of polyreactive antibodies with innate specificity, questioning its capacity to select resident microbiota.
PB  - John Wiley and Sons Inc
T2  - Scandinavian Journal of Immunology
T1  - Selectivity of polyclonal repertoire of anti-microbial IgA and its subclasses in saliva and serum in humans
VL  - 96
IS  - 6
DO  - 10.1111/sji.13223
ER  - 
@article{
author = "Nikodijević, Slavomir and Blagojević, Veljko and Ćuruvija, Ivana and Kosanović, Dejana and Đukić, Tamara and Đorđević, Brižita and Ilić, Vesna and Minić, Rajna",
year = "2022",
abstract = "Increased interest in microbiota calls for the thorough analysis of antibody reactivity to different microorganisms. As salivary IgA represents the first line of defence against microorganisms contacting mucosal surfaces, we explored the binding and specificity of salivary IgA by testing the binding of purified, FITC-labelled salivary IgA to different microorganisms in flow cytometry and conclude that this kind of analysis enables the differentiation of species/strains with high IgA binding capacity, which should be corroborated on a larger sample size. Further we compare, with in-house ELISA, the binding of polyclonal salivary IgA with the binding of polyclonal serum IgA from the same individuals to whole microbial cells and to purified microbial components. High correlations were obtained in total salivary IgA binding to Lactobacillus rhamnosus and Escherichia coli, very distant bacterial species, as well as to isolated bacterial components (r =.70–.97). The binding of total salivary IgA resembled the binding of both salivary IgA1 and IgA2, with IgA2 predominating. For serum polyclonal IgA repertoire, substantially higher specificity was obtained. Serum IgA binding to E. coli correlated best with serum IgA binding to lipopolysaccharide (r =.86), and serum IgA against L. rhamnosus correlated best with the anti-peptidoglycan IgA levels (r =.88). We have also detected that total serum IgA response is governed by either IgA1 or IgA2 response, depending on the nature of the antigen/s. We conclude that steady state salivary IgA repertoire, unlike serum IgA repertoire, consists of polyreactive antibodies with innate specificity, questioning its capacity to select resident microbiota.",
publisher = "John Wiley and Sons Inc",
journal = "Scandinavian Journal of Immunology",
title = "Selectivity of polyclonal repertoire of anti-microbial IgA and its subclasses in saliva and serum in humans",
volume = "96",
number = "6",
doi = "10.1111/sji.13223"
}
Nikodijević, S., Blagojević, V., Ćuruvija, I., Kosanović, D., Đukić, T., Đorđević, B., Ilić, V.,& Minić, R.. (2022). Selectivity of polyclonal repertoire of anti-microbial IgA and its subclasses in saliva and serum in humans. in Scandinavian Journal of Immunology
John Wiley and Sons Inc., 96(6).
https://doi.org/10.1111/sji.13223
Nikodijević S, Blagojević V, Ćuruvija I, Kosanović D, Đukić T, Đorđević B, Ilić V, Minić R. Selectivity of polyclonal repertoire of anti-microbial IgA and its subclasses in saliva and serum in humans. in Scandinavian Journal of Immunology. 2022;96(6).
doi:10.1111/sji.13223 .
Nikodijević, Slavomir, Blagojević, Veljko, Ćuruvija, Ivana, Kosanović, Dejana, Đukić, Tamara, Đorđević, Brižita, Ilić, Vesna, Minić, Rajna, "Selectivity of polyclonal repertoire of anti-microbial IgA and its subclasses in saliva and serum in humans" in Scandinavian Journal of Immunology, 96, no. 6 (2022),
https://doi.org/10.1111/sji.13223 . .
1

Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention

Ružić, Dušan; Đoković, Nemanja; Srdić-Rajić, Tatjana; Echeverria, Cesar; Nikolić, Katarina; Santibanez, Juan

(MDPI, 2022)

TY  - JOUR
AU  - Ružić, Dušan
AU  - Đoković, Nemanja
AU  - Srdić-Rajić, Tatjana
AU  - Echeverria, Cesar
AU  - Nikolić, Katarina
AU  - Santibanez, Juan
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4025
AB  - The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death programs. Over the last three decades, an increasing number of synthetic and naturally derived compounds, such as dietary-derived products, have been demonstrated to act as HDACi and have provided biological and molecular insights with regard to the role of HDAC in cancer. The first part of this review is focused on the biological roles of the Zinc-dependent HDAC family in malignant diseases. Accordingly, the small-molecules and natural products such as HDACi are described in terms of cancer therapy and chemoprevention. Furthermore, structural considerations are included to improve the HDACi selectivity and combinatory potential with other specific targeting agents in bifunctional inhibitors and proteolysis targeting chimeras. Additionally, clinical trials that combine HDACi with current therapies are discussed, which may open new avenues in terms of the feasibility of HDACi’s future clinical applications in precision cancer therapies.
PB  - MDPI
T2  - Pharmaceutics
T1  - Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention
VL  - 14
IS  - 1
DO  - 10.3390/pharmaceutics14010209
ER  - 
@article{
author = "Ružić, Dušan and Đoković, Nemanja and Srdić-Rajić, Tatjana and Echeverria, Cesar and Nikolić, Katarina and Santibanez, Juan",
year = "2022",
abstract = "The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death programs. Over the last three decades, an increasing number of synthetic and naturally derived compounds, such as dietary-derived products, have been demonstrated to act as HDACi and have provided biological and molecular insights with regard to the role of HDAC in cancer. The first part of this review is focused on the biological roles of the Zinc-dependent HDAC family in malignant diseases. Accordingly, the small-molecules and natural products such as HDACi are described in terms of cancer therapy and chemoprevention. Furthermore, structural considerations are included to improve the HDACi selectivity and combinatory potential with other specific targeting agents in bifunctional inhibitors and proteolysis targeting chimeras. Additionally, clinical trials that combine HDACi with current therapies are discussed, which may open new avenues in terms of the feasibility of HDACi’s future clinical applications in precision cancer therapies.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention",
volume = "14",
number = "1",
doi = "10.3390/pharmaceutics14010209"
}
Ružić, D., Đoković, N., Srdić-Rajić, T., Echeverria, C., Nikolić, K.,& Santibanez, J.. (2022). Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention. in Pharmaceutics
MDPI., 14(1).
https://doi.org/10.3390/pharmaceutics14010209
Ružić D, Đoković N, Srdić-Rajić T, Echeverria C, Nikolić K, Santibanez J. Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention. in Pharmaceutics. 2022;14(1).
doi:10.3390/pharmaceutics14010209 .
Ružić, Dušan, Đoković, Nemanja, Srdić-Rajić, Tatjana, Echeverria, Cesar, Nikolić, Katarina, Santibanez, Juan, "Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention" in Pharmaceutics, 14, no. 1 (2022),
https://doi.org/10.3390/pharmaceutics14010209 . .
11
29
2
26

Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension

Kurćubić, Ivana; Vajić, Una‐Jovana; Cvijić, Sandra; Crevar-Sakač, Milkica; Ibrić, Svetlana; Miloradović, Zoran; Mihailović‐Stanojević, Nevena; Ivanov, Milan; Karanović, Danijela; Jovović, Đurđica; Đuriš, Jelena

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Kurćubić, Ivana
AU  - Vajić, Una‐Jovana
AU  - Cvijić, Sandra
AU  - Crevar-Sakač, Milkica
AU  - Ibrić, Svetlana
AU  - Miloradović, Zoran
AU  - Mihailović‐Stanojević, Nevena
AU  - Ivanov, Milan
AU  - Karanović, Danijela
AU  - Jovović, Đurđica
AU  - Đuriš, Jelena
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4512
AB  - Mucoadhesive buccal films can improve drug absorption by prolonging its retention
time on the buccal mucosa (1). The aim of the study was a comparative assessment of the
hemodynamic effects and pharmacokinetics of propranolol hydrochloride (PROP) after
buccal and oral administration in spontaneously hypertensive rats. Animals were divided
into 3 groups: Group I (control) received 0.5 mL of water with a gastric tube, group II
received an immediate-release 10 mg PROP tablet via gastric tube, and group III received a
mucoadhesive 10 mg PROP buccal film. Systolic (SP) and diastolic blood pressure (DP), and
heart rate (SF) were measured in rats, and pharmacokinetic PROP parameters, Cmax, tmax,
and AUC0 → 24, were calculated by noncompartmental analysis. Mucoadhesive buccal films
showed superior degree of absorption of PROP over immediate-release tablets (AUC0 → 24:
69.64 μgh/ml versus 24.61 μgh/ml). The tmax value was significantly higher in
mucoadhesive buccal films, which indicates a prolonged PROP release and longer
therapeutic effect (71.19h versus 29.73h). There was no statistically significant difference in
Cmax values between groups II and III of rats (4.74 μg ml versus 7.11 μg ml). Mucoadhesive
buccal films provide a more pronounced and long-lasting reduction primarily of SF
(reduction of 28-51% lasting from 10 minutes to the twelfth hour of testing), but also SP and
DP (between 15-30% from the first to the sixth hour of testing) compared to immediate-
release tablets. Mucoadhesive buccal films allow bypass/reduction of the extensive hepatic
first-pass metabolism, and consequently improve the therapeutic PROP effect.
AB  - Mukoadhezivni bukalni filmovi mogu poboljšati apsorpciju lekovite supstance
produžavajuć i vreme zadržavanja lekovitog preparata na bukalnoj sluznici (1). Cilj studije je
bila komparativna procena hemodinamskih efekata i farmakokinetike propranolol-
hidrohlorida (PROP) nakon bukalne i peroralne primene kod sponatano hipertenzivnih
pacova. Spontano hipertenzivni pacovi su podeljeni u 3 grupe: I (kontrolna) grupa je dobila
0,5 mL vode gastričnom sondom, II grupa je dobila tabletu sa trenutnim oslobađanjem sa 10
mg PROP gastričnom sondom i III grupa je dobila mukoadhezivni bukalni film sa 10 mg
PROP. Filmovi su pripremljeni korišćenjem polietilenoksida, hidroksipropilmetilceluloze i
polivinilalkohola kao film-formirajućih polimera sa mukoadhezivnim svojstvima. Pacovima
su mereni sistolni (SP) i dijastolni krvni pritisak (DP), srčana frekvencija (SF), a
neprostornom farmakokinetičkom analizom izračunati su parametri PROP: Cmax, t max i
AUC0→24 . Mukoadhezivni bukalni filmovi su pokazali superiornost u odnosu na tablete sa
trenutnim oslobađanjem u pogledu stepena apsorpcije PROP (AUC 0→24 : 69,64 μgh/ml
naspram 24,61 μgh/ml). Tmax vrednost je bila značajno veća kod mukoadhezivnih bukalnih
filmova što ukazuje na produženo oslobađanje PROP i duži terapijski efekat (71,19 h
naspram 29,73 h). Između II i II grupe pacova nema statistički značajne razlike u
vrednostima Cmax (4,74 μg/ml naspram 7,11 μg/ml). Mukoadhezivni bukalni filmovi izazivaju
izraženije i dugotrajnije smanjenje pre svega SF (smanjenje od 28-51% u trajanju od 10
minuta do dvanaestog sata ispitivanja), ali i SP i DP (između 15-30% od prvog do šestog sata
ispitivanja) u odnosu na tablete sa trenutnim oslobađanjem. Pripremljeni mukoadhezivni
bukalni filmovi omogućavaju zaobilazak/smanjenje ekstenzivnog metabolizma prvog
prolaza kroz jetru i posledično poboljšavaju terapijski efekat PROP.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension
T1  - Efekti akutne primene mukoadhezivnih bukalnih filmova sa propranolol‐hidrohloridom u animalnom modelu esencijalne hipertenzije
VL  - 72
IS  - 4 suplement
SP  - S235
EP  - S236
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4512
ER  - 
@conference{
author = "Kurćubić, Ivana and Vajić, Una‐Jovana and Cvijić, Sandra and Crevar-Sakač, Milkica and Ibrić, Svetlana and Miloradović, Zoran and Mihailović‐Stanojević, Nevena and Ivanov, Milan and Karanović, Danijela and Jovović, Đurđica and Đuriš, Jelena",
year = "2022",
abstract = "Mucoadhesive buccal films can improve drug absorption by prolonging its retention
time on the buccal mucosa (1). The aim of the study was a comparative assessment of the
hemodynamic effects and pharmacokinetics of propranolol hydrochloride (PROP) after
buccal and oral administration in spontaneously hypertensive rats. Animals were divided
into 3 groups: Group I (control) received 0.5 mL of water with a gastric tube, group II
received an immediate-release 10 mg PROP tablet via gastric tube, and group III received a
mucoadhesive 10 mg PROP buccal film. Systolic (SP) and diastolic blood pressure (DP), and
heart rate (SF) were measured in rats, and pharmacokinetic PROP parameters, Cmax, tmax,
and AUC0 → 24, were calculated by noncompartmental analysis. Mucoadhesive buccal films
showed superior degree of absorption of PROP over immediate-release tablets (AUC0 → 24:
69.64 μgh/ml versus 24.61 μgh/ml). The tmax value was significantly higher in
mucoadhesive buccal films, which indicates a prolonged PROP release and longer
therapeutic effect (71.19h versus 29.73h). There was no statistically significant difference in
Cmax values between groups II and III of rats (4.74 μg ml versus 7.11 μg ml). Mucoadhesive
buccal films provide a more pronounced and long-lasting reduction primarily of SF
(reduction of 28-51% lasting from 10 minutes to the twelfth hour of testing), but also SP and
DP (between 15-30% from the first to the sixth hour of testing) compared to immediate-
release tablets. Mucoadhesive buccal films allow bypass/reduction of the extensive hepatic
first-pass metabolism, and consequently improve the therapeutic PROP effect., Mukoadhezivni bukalni filmovi mogu poboljšati apsorpciju lekovite supstance
produžavajuć i vreme zadržavanja lekovitog preparata na bukalnoj sluznici (1). Cilj studije je
bila komparativna procena hemodinamskih efekata i farmakokinetike propranolol-
hidrohlorida (PROP) nakon bukalne i peroralne primene kod sponatano hipertenzivnih
pacova. Spontano hipertenzivni pacovi su podeljeni u 3 grupe: I (kontrolna) grupa je dobila
0,5 mL vode gastričnom sondom, II grupa je dobila tabletu sa trenutnim oslobađanjem sa 10
mg PROP gastričnom sondom i III grupa je dobila mukoadhezivni bukalni film sa 10 mg
PROP. Filmovi su pripremljeni korišćenjem polietilenoksida, hidroksipropilmetilceluloze i
polivinilalkohola kao film-formirajućih polimera sa mukoadhezivnim svojstvima. Pacovima
su mereni sistolni (SP) i dijastolni krvni pritisak (DP), srčana frekvencija (SF), a
neprostornom farmakokinetičkom analizom izračunati su parametri PROP: Cmax, t max i
AUC0→24 . Mukoadhezivni bukalni filmovi su pokazali superiornost u odnosu na tablete sa
trenutnim oslobađanjem u pogledu stepena apsorpcije PROP (AUC 0→24 : 69,64 μgh/ml
naspram 24,61 μgh/ml). Tmax vrednost je bila značajno veća kod mukoadhezivnih bukalnih
filmova što ukazuje na produženo oslobađanje PROP i duži terapijski efekat (71,19 h
naspram 29,73 h). Između II i II grupe pacova nema statistički značajne razlike u
vrednostima Cmax (4,74 μg/ml naspram 7,11 μg/ml). Mukoadhezivni bukalni filmovi izazivaju
izraženije i dugotrajnije smanjenje pre svega SF (smanjenje od 28-51% u trajanju od 10
minuta do dvanaestog sata ispitivanja), ali i SP i DP (između 15-30% od prvog do šestog sata
ispitivanja) u odnosu na tablete sa trenutnim oslobađanjem. Pripremljeni mukoadhezivni
bukalni filmovi omogućavaju zaobilazak/smanjenje ekstenzivnog metabolizma prvog
prolaza kroz jetru i posledično poboljšavaju terapijski efekat PROP.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension, Efekti akutne primene mukoadhezivnih bukalnih filmova sa propranolol‐hidrohloridom u animalnom modelu esencijalne hipertenzije",
volume = "72",
number = "4 suplement",
pages = "S235-S236",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4512"
}
Kurćubić, I., Vajić, U., Cvijić, S., Crevar-Sakač, M., Ibrić, S., Miloradović, Z., Mihailović‐Stanojević, N., Ivanov, M., Karanović, D., Jovović, Đ.,& Đuriš, J.. (2022). Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S235-S236.
https://hdl.handle.net/21.15107/rcub_farfar_4512
Kurćubić I, Vajić U, Cvijić S, Crevar-Sakač M, Ibrić S, Miloradović Z, Mihailović‐Stanojević N, Ivanov M, Karanović D, Jovović Đ, Đuriš J. Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension. in Arhiv za farmaciju. 2022;72(4 suplement):S235-S236.
https://hdl.handle.net/21.15107/rcub_farfar_4512 .
Kurćubić, Ivana, Vajić, Una‐Jovana, Cvijić, Sandra, Crevar-Sakač, Milkica, Ibrić, Svetlana, Miloradović, Zoran, Mihailović‐Stanojević, Nevena, Ivanov, Milan, Karanović, Danijela, Jovović, Đurđica, Đuriš, Jelena, "Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S235-S236,
https://hdl.handle.net/21.15107/rcub_farfar_4512 .

Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension

Kurćubić, Ivana; Vajić, Una-Jovana; Cvijić, Sandra; Crevar-Sakač, Milkica; Bogavac-Stanojević, Nataša; Miloradović, Zoran; Mihajlović-Stanojević, Nevena; Ivanov, Milan; Karanović, Danijela; Jovović, Đurđica; Đuriš, Jelena

(Elsevier B.V., 2021)

TY  - JOUR
AU  - Kurćubić, Ivana
AU  - Vajić, Una-Jovana
AU  - Cvijić, Sandra
AU  - Crevar-Sakač, Milkica
AU  - Bogavac-Stanojević, Nataša
AU  - Miloradović, Zoran
AU  - Mihajlović-Stanojević, Nevena
AU  - Ivanov, Milan
AU  - Karanović, Danijela
AU  - Jovović, Đurđica
AU  - Đuriš, Jelena
PY  - 2021
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3990
AB  - The objective of this study was to formulate extended-release mucoadhesive buccal tablets of propranolol hydrochloride in order to provide a prolonged absorption of propranolol hydrochloride from the buccal mucosa and to reduce presystemic metabolism and thus provide a better therapeutic effect. Besides, the aim was to perform comparative in vivo pharmacokinetic and hemodynamic studies of the developed extended-release (ER) propranolol hydrochloride 10 mg mucoadhesive buccal tablets and commercial immediate-release (IR) propranolol hydrochloride 10 mg tablets in spontaneously hypertensive rats. Formulation with 15% polyethylene oxide showed the highest degree of propranolol hydrochloride permeation, satisfactory mucoadhesiveness, and extended-release of propranolol hydrochloride, thus it was selected for further in vivo study. The pharmacokinetic study in rats showed the superiority of ER mucoadhesive buccal tablets over IR tablets in terms of propranolol hydrochloride absorption extent (AUC values: 70.32 ± 19.56 versus 31.69 ± 6.97 μg⋅h/mL), although lower maximum plasma propranolol hydrochloride concentration (Cmax) was achieved. However, no statistically significant difference was observed in Cmax between these treatments. The hemodynamic study showed that ER mucoadhesive buccal tablets provide a more pronounced decrease primarily in heart rate, but also in systolic and diastolic arterial pressure, as well as a longer heart rate reduction compared to IR tablets.
PB  - Elsevier B.V.
T2  - International Journal of Pharmaceutics
T1  - Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension
VL  - 610
DO  - 10.1016/j.ijpharm.2021.121266
ER  - 
@article{
author = "Kurćubić, Ivana and Vajić, Una-Jovana and Cvijić, Sandra and Crevar-Sakač, Milkica and Bogavac-Stanojević, Nataša and Miloradović, Zoran and Mihajlović-Stanojević, Nevena and Ivanov, Milan and Karanović, Danijela and Jovović, Đurđica and Đuriš, Jelena",
year = "2021, 2021",
abstract = "The objective of this study was to formulate extended-release mucoadhesive buccal tablets of propranolol hydrochloride in order to provide a prolonged absorption of propranolol hydrochloride from the buccal mucosa and to reduce presystemic metabolism and thus provide a better therapeutic effect. Besides, the aim was to perform comparative in vivo pharmacokinetic and hemodynamic studies of the developed extended-release (ER) propranolol hydrochloride 10 mg mucoadhesive buccal tablets and commercial immediate-release (IR) propranolol hydrochloride 10 mg tablets in spontaneously hypertensive rats. Formulation with 15% polyethylene oxide showed the highest degree of propranolol hydrochloride permeation, satisfactory mucoadhesiveness, and extended-release of propranolol hydrochloride, thus it was selected for further in vivo study. The pharmacokinetic study in rats showed the superiority of ER mucoadhesive buccal tablets over IR tablets in terms of propranolol hydrochloride absorption extent (AUC values: 70.32 ± 19.56 versus 31.69 ± 6.97 μg⋅h/mL), although lower maximum plasma propranolol hydrochloride concentration (Cmax) was achieved. However, no statistically significant difference was observed in Cmax between these treatments. The hemodynamic study showed that ER mucoadhesive buccal tablets provide a more pronounced decrease primarily in heart rate, but also in systolic and diastolic arterial pressure, as well as a longer heart rate reduction compared to IR tablets.",
publisher = "Elsevier B.V.",
journal = "International Journal of Pharmaceutics",
title = "Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension",
volume = "610",
doi = "10.1016/j.ijpharm.2021.121266"
}
Kurćubić, I., Vajić, U., Cvijić, S., Crevar-Sakač, M., Bogavac-Stanojević, N., Miloradović, Z., Mihajlović-Stanojević, N., Ivanov, M., Karanović, D., Jovović, Đ.,& Đuriš, J.. (2021). Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension. in International Journal of Pharmaceutics
Elsevier B.V.., 610.
https://doi.org/10.1016/j.ijpharm.2021.121266
Kurćubić I, Vajić U, Cvijić S, Crevar-Sakač M, Bogavac-Stanojević N, Miloradović Z, Mihajlović-Stanojević N, Ivanov M, Karanović D, Jovović Đ, Đuriš J. Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension. in International Journal of Pharmaceutics. 2021;610.
doi:10.1016/j.ijpharm.2021.121266 .
Kurćubić, Ivana, Vajić, Una-Jovana, Cvijić, Sandra, Crevar-Sakač, Milkica, Bogavac-Stanojević, Nataša, Miloradović, Zoran, Mihajlović-Stanojević, Nevena, Ivanov, Milan, Karanović, Danijela, Jovović, Đurđica, Đuriš, Jelena, "Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension" in International Journal of Pharmaceutics, 610 (2021),
https://doi.org/10.1016/j.ijpharm.2021.121266 . .
6
5

DNA, protein and lipid oxidative damage in tissues of spontaneously hypertensive versus normotensive rats

Bruić, Marija; Grujić-Milanović, Jelica; Miloradović, Zoran; Jovović, Đurđica; Živković, Lada; Mihailović-Stanojević, Nevena; Karanović, Danijela; Spremo-Potparević, Biljana

(Elsevier Ltd, 2021)

TY  - JOUR
AU  - Bruić, Marija
AU  - Grujić-Milanović, Jelica
AU  - Miloradović, Zoran
AU  - Jovović, Đurđica
AU  - Živković, Lada
AU  - Mihailović-Stanojević, Nevena
AU  - Karanović, Danijela
AU  - Spremo-Potparević, Biljana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3981
AB  - Oxidative damage to protein and lipid macromolecules in target organs in hypertension has been recognized as a major factor contributing to cardiovascular, cerebrovascular, and renal diseases. Data on protein and lipid oxidative damage in spontaneously hypertensive rats are numerous, but there is no information on DNA damage in tissues measured by comet assay. The aim of this study was to determine the baseline damage to DNA, protein, and lipid macromolecules in different organs of spontaneously hypertensive rats. Markers of lipid peroxidation, protein oxidation, and DNA damage were measured in blood, heart, kidney, and liver of 24-week-old spontaneously hypertensive rats. Plasma prooxidant and antioxidant status were determined as well. Age-matched normotensive Wistar rats were used as control. A rise in markers of lipid peroxidation and protein oxidation, malondialdehyde, and advanced oxidation protein products, was detected in all tissues of spontaneously hypertensive rats, with particularly high values in the liver. DNA damage, measured by the comet assay, was significantly higher in all the studied tissues of spontaneously hypertensive rats compared to normotensive control, with more severe damage in the cardiac and renal cells. Significant depletion of the plasma antioxidant barrier in spontaneously hypertensive rats was also observed. This study showed increased damage to all macromolecules in all studied samples of spontaneously hypertensive rats in comparison with control Wistar rats.
PB  - Elsevier Ltd
T2  - International Journal of Biochemistry and Cell Biology
T1  - DNA, protein and lipid oxidative damage in tissues of spontaneously hypertensive versus normotensive rats
VL  - 141
DO  - 10.1016/j.biocel.2021.106088
ER  - 
@article{
author = "Bruić, Marija and Grujić-Milanović, Jelica and Miloradović, Zoran and Jovović, Đurđica and Živković, Lada and Mihailović-Stanojević, Nevena and Karanović, Danijela and Spremo-Potparević, Biljana",
year = "2021",
abstract = "Oxidative damage to protein and lipid macromolecules in target organs in hypertension has been recognized as a major factor contributing to cardiovascular, cerebrovascular, and renal diseases. Data on protein and lipid oxidative damage in spontaneously hypertensive rats are numerous, but there is no information on DNA damage in tissues measured by comet assay. The aim of this study was to determine the baseline damage to DNA, protein, and lipid macromolecules in different organs of spontaneously hypertensive rats. Markers of lipid peroxidation, protein oxidation, and DNA damage were measured in blood, heart, kidney, and liver of 24-week-old spontaneously hypertensive rats. Plasma prooxidant and antioxidant status were determined as well. Age-matched normotensive Wistar rats were used as control. A rise in markers of lipid peroxidation and protein oxidation, malondialdehyde, and advanced oxidation protein products, was detected in all tissues of spontaneously hypertensive rats, with particularly high values in the liver. DNA damage, measured by the comet assay, was significantly higher in all the studied tissues of spontaneously hypertensive rats compared to normotensive control, with more severe damage in the cardiac and renal cells. Significant depletion of the plasma antioxidant barrier in spontaneously hypertensive rats was also observed. This study showed increased damage to all macromolecules in all studied samples of spontaneously hypertensive rats in comparison with control Wistar rats.",
publisher = "Elsevier Ltd",
journal = "International Journal of Biochemistry and Cell Biology",
title = "DNA, protein and lipid oxidative damage in tissues of spontaneously hypertensive versus normotensive rats",
volume = "141",
doi = "10.1016/j.biocel.2021.106088"
}
Bruić, M., Grujić-Milanović, J., Miloradović, Z., Jovović, Đ., Živković, L., Mihailović-Stanojević, N., Karanović, D.,& Spremo-Potparević, B.. (2021). DNA, protein and lipid oxidative damage in tissues of spontaneously hypertensive versus normotensive rats. in International Journal of Biochemistry and Cell Biology
Elsevier Ltd., 141.
https://doi.org/10.1016/j.biocel.2021.106088
Bruić M, Grujić-Milanović J, Miloradović Z, Jovović Đ, Živković L, Mihailović-Stanojević N, Karanović D, Spremo-Potparević B. DNA, protein and lipid oxidative damage in tissues of spontaneously hypertensive versus normotensive rats. in International Journal of Biochemistry and Cell Biology. 2021;141.
doi:10.1016/j.biocel.2021.106088 .
Bruić, Marija, Grujić-Milanović, Jelica, Miloradović, Zoran, Jovović, Đurđica, Živković, Lada, Mihailović-Stanojević, Nevena, Karanović, Danijela, Spremo-Potparević, Biljana, "DNA, protein and lipid oxidative damage in tissues of spontaneously hypertensive versus normotensive rats" in International Journal of Biochemistry and Cell Biology, 141 (2021),
https://doi.org/10.1016/j.biocel.2021.106088 . .
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