Mladenović, Dušan

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  • Mladenović, Dušan (4)
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Author's Bibliography

Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover

Vasović, Dolika D.; Ivković, Sanja; Živanović, Ana; Major, Tamara; Milašin, Jelena M.; Nikolić, Nađa S.; Simonović, Jelena; Šutulović, Nikola; Hrnčić, Dragan; Stanojlović, Olivera; Vesković, Milena; Rašić, Dejan M.; Mladenović, Dušan

(Elsevier, 2024)

TY  - JOUR
AU  - Vasović, Dolika D.
AU  - Ivković, Sanja
AU  - Živanović, Ana
AU  - Major, Tamara
AU  - Milašin, Jelena M.
AU  - Nikolić, Nađa S.
AU  - Simonović, Jelena
AU  - Šutulović, Nikola
AU  - Hrnčić, Dragan
AU  - Stanojlović, Olivera
AU  - Vesković, Milena
AU  - Rašić, Dejan M.
AU  - Mladenović, Dušan
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5611
AB  - Diabetic retinopathy is not cured efficiently and changes of lifestyle measures may delay early retinal injury in
diabetes. The aim of our study was to investigate the effects of reduced daily light exposure on retinal vascular
changes in streptozotocin (STZ)-induced model of DM with emphasis on inflammation, Aqp4 expression, visual
cycle and cholesterol metabolism-related gene expression in rat retina and RPE. Male Wistar rats were divided
into the following groups: 1. control; 2. diabetic group (DM) treated with streptozotocin (100 mg/kg); 3. group
exposed to light/dark cycle 6/18 h (6/18); 4. diabetic group exposed to light/dark cycle 6/18 h (DM+6/18).
Retinal vascular abnormalities were estimated based on lectin staining, while the expression of genes involved in
the visual cycle, cholesterol metabolism, and inflammation was determined by qRT-PCR. Reduced light exposure
alleviated vasculopathy, gliosis and the expression of IL-1 and TNF-α in the retina with increased perivascular
Aqp4 expression. The expression of genes involved in visual cycle and cholesterol metabolism was significantly
up-regulated in RPE in DM+6/18 vs. DM group. In the retina only the expression of APOE was significantly
higher in DM+6/18 vs. DM group. Reduced light exposure mitigates vascular changes and gliosis in DM via its
anti-inflammatory effect, increased retinal cholesterol turnover and perivascular Aqp4 expression.
PB  - Elsevier
T2  - Chemico-Biological Interactions
T1  - Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover
VL  - 394
SP  - 110996
DO  - 10.1016/j.cbi.2024.110996
ER  - 
@article{
author = "Vasović, Dolika D. and Ivković, Sanja and Živanović, Ana and Major, Tamara and Milašin, Jelena M. and Nikolić, Nađa S. and Simonović, Jelena and Šutulović, Nikola and Hrnčić, Dragan and Stanojlović, Olivera and Vesković, Milena and Rašić, Dejan M. and Mladenović, Dušan",
year = "2024",
abstract = "Diabetic retinopathy is not cured efficiently and changes of lifestyle measures may delay early retinal injury in
diabetes. The aim of our study was to investigate the effects of reduced daily light exposure on retinal vascular
changes in streptozotocin (STZ)-induced model of DM with emphasis on inflammation, Aqp4 expression, visual
cycle and cholesterol metabolism-related gene expression in rat retina and RPE. Male Wistar rats were divided
into the following groups: 1. control; 2. diabetic group (DM) treated with streptozotocin (100 mg/kg); 3. group
exposed to light/dark cycle 6/18 h (6/18); 4. diabetic group exposed to light/dark cycle 6/18 h (DM+6/18).
Retinal vascular abnormalities were estimated based on lectin staining, while the expression of genes involved in
the visual cycle, cholesterol metabolism, and inflammation was determined by qRT-PCR. Reduced light exposure
alleviated vasculopathy, gliosis and the expression of IL-1 and TNF-α in the retina with increased perivascular
Aqp4 expression. The expression of genes involved in visual cycle and cholesterol metabolism was significantly
up-regulated in RPE in DM+6/18 vs. DM group. In the retina only the expression of APOE was significantly
higher in DM+6/18 vs. DM group. Reduced light exposure mitigates vascular changes and gliosis in DM via its
anti-inflammatory effect, increased retinal cholesterol turnover and perivascular Aqp4 expression.",
publisher = "Elsevier",
journal = "Chemico-Biological Interactions",
title = "Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover",
volume = "394",
pages = "110996",
doi = "10.1016/j.cbi.2024.110996"
}
Vasović, D. D., Ivković, S., Živanović, A., Major, T., Milašin, J. M., Nikolić, N. S., Simonović, J., Šutulović, N., Hrnčić, D., Stanojlović, O., Vesković, M., Rašić, D. M.,& Mladenović, D.. (2024). Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover. in Chemico-Biological Interactions
Elsevier., 394, 110996.
https://doi.org/10.1016/j.cbi.2024.110996
Vasović DD, Ivković S, Živanović A, Major T, Milašin JM, Nikolić NS, Simonović J, Šutulović N, Hrnčić D, Stanojlović O, Vesković M, Rašić DM, Mladenović D. Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover. in Chemico-Biological Interactions. 2024;394:110996.
doi:10.1016/j.cbi.2024.110996 .
Vasović, Dolika D., Ivković, Sanja, Živanović, Ana, Major, Tamara, Milašin, Jelena M., Nikolić, Nađa S., Simonović, Jelena, Šutulović, Nikola, Hrnčić, Dragan, Stanojlović, Olivera, Vesković, Milena, Rašić, Dejan M., Mladenović, Dušan, "Reduced light exposure mitigates streptozotocin-induced vascular changes and gliosis in diabetic retina by an anti-inflammatory effect and increased retinal cholesterol turnover" in Chemico-Biological Interactions, 394 (2024):110996,
https://doi.org/10.1016/j.cbi.2024.110996 . .

The effect of cannabinoid receptor 1 blockade on hepatic free fatty acid profile in mice with nonalcoholic fatty liver disease

Jorgačević, B; Vučević, D; Đuričić, Ivana; Šobajić, Slađana; Mladenović, Dušan; Vesković, M; Vukićević, R.J; Radosavljević, Tatjana S.

(Elsevier Ireland Ltd, 2017)

TY  - JOUR
AU  - Jorgačević, B
AU  - Vučević, D
AU  - Đuričić, Ivana
AU  - Šobajić, Slađana
AU  - Mladenović, Dušan
AU  - Vesković, M
AU  - Vukićević, R.J
AU  - Radosavljević, Tatjana S.
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2915
AB  - We used rimonabant to investigate the role of CB1 receptor on hepatic FFAs profile during NAFLD. Male mice C57BL/6 were divided into: control group fed with control diet 20 weeks (C; n = 6); group fed with HFD 20 weeks (HF; n = 6); group fed with control diet and treated with rimonabant after 18 weeks (R; n = 9); group fed with HFD and treated with rimonabant after 18 weeks (HFR; n = 10). Rimonabant (10 mg/kg) was administered daily to HFR and R group by oral gavage. Rimonabant decreased liver palmitic acid proportion in HFR group compared to HF group (p  lt  0.05). Liver stearic and oleic acid proportions were decreased in R group compared to control (p  lt  0.01 respectively). Rimonabant increased liver linoleic and arachidonic acid proportions in HFR group compared to HF group (p  lt  0.01 respectively). CB1 blockade may be useful in the treatment of HFD-induced NAFLD due to modulation of plasma lipid and hepatic FFA profile.
PB  - Elsevier Ireland Ltd
T2  - Chemistry and Physics of Lipids
T1  - The effect of cannabinoid receptor 1 blockade on hepatic free fatty acid profile in mice with nonalcoholic fatty liver disease
VL  - 204
SP  - 85
EP  - 93
DO  - 10.1016/j.chemphyslip.2017.03.009
ER  - 
@article{
author = "Jorgačević, B and Vučević, D and Đuričić, Ivana and Šobajić, Slađana and Mladenović, Dušan and Vesković, M and Vukićević, R.J and Radosavljević, Tatjana S.",
year = "2017",
abstract = "We used rimonabant to investigate the role of CB1 receptor on hepatic FFAs profile during NAFLD. Male mice C57BL/6 were divided into: control group fed with control diet 20 weeks (C; n = 6); group fed with HFD 20 weeks (HF; n = 6); group fed with control diet and treated with rimonabant after 18 weeks (R; n = 9); group fed with HFD and treated with rimonabant after 18 weeks (HFR; n = 10). Rimonabant (10 mg/kg) was administered daily to HFR and R group by oral gavage. Rimonabant decreased liver palmitic acid proportion in HFR group compared to HF group (p  lt  0.05). Liver stearic and oleic acid proportions were decreased in R group compared to control (p  lt  0.01 respectively). Rimonabant increased liver linoleic and arachidonic acid proportions in HFR group compared to HF group (p  lt  0.01 respectively). CB1 blockade may be useful in the treatment of HFD-induced NAFLD due to modulation of plasma lipid and hepatic FFA profile.",
publisher = "Elsevier Ireland Ltd",
journal = "Chemistry and Physics of Lipids",
title = "The effect of cannabinoid receptor 1 blockade on hepatic free fatty acid profile in mice with nonalcoholic fatty liver disease",
volume = "204",
pages = "85-93",
doi = "10.1016/j.chemphyslip.2017.03.009"
}
Jorgačević, B., Vučević, D., Đuričić, I., Šobajić, S., Mladenović, D., Vesković, M., Vukićević, R.J,& Radosavljević, T. S.. (2017). The effect of cannabinoid receptor 1 blockade on hepatic free fatty acid profile in mice with nonalcoholic fatty liver disease. in Chemistry and Physics of Lipids
Elsevier Ireland Ltd., 204, 85-93.
https://doi.org/10.1016/j.chemphyslip.2017.03.009
Jorgačević B, Vučević D, Đuričić I, Šobajić S, Mladenović D, Vesković M, Vukićević R, Radosavljević TS. The effect of cannabinoid receptor 1 blockade on hepatic free fatty acid profile in mice with nonalcoholic fatty liver disease. in Chemistry and Physics of Lipids. 2017;204:85-93.
doi:10.1016/j.chemphyslip.2017.03.009 .
Jorgačević, B, Vučević, D, Đuričić, Ivana, Šobajić, Slađana, Mladenović, Dušan, Vesković, M, Vukićević, R.J, Radosavljević, Tatjana S., "The effect of cannabinoid receptor 1 blockade on hepatic free fatty acid profile in mice with nonalcoholic fatty liver disease" in Chemistry and Physics of Lipids, 204 (2017):85-93,
https://doi.org/10.1016/j.chemphyslip.2017.03.009 . .
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The Effects of alpha-Lipoic Acid on Liver Oxidative Stress and Free Fatty Acid Composition in Methionine-Choline Deficient Diet-Induced NAFLD

Stanković, Milena N.; Mladenović, Dušan; Ninković, Milica; Đuričić, Ivana; Šobajić, Slađana; Jorgacević, Bojan; de Luka, Silvio; Jesić-Vukicević, Rada; Radosavljević, Tatjana S.

(Mary Ann Liebert, Inc, New Rochelle, 2014)

TY  - JOUR
AU  - Stanković, Milena N.
AU  - Mladenović, Dušan
AU  - Ninković, Milica
AU  - Đuričić, Ivana
AU  - Šobajić, Slađana
AU  - Jorgacević, Bojan
AU  - de Luka, Silvio
AU  - Jesić-Vukicević, Rada
AU  - Radosavljević, Tatjana S.
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2176
AB  - Development of nonalcoholic fatty liver disease (NAFLD) occurs through initial steatosis and subsequent oxidative stress. The aim of this study was to examine the effects of -lipoic acid (LA) on methionine-choline deficient (MCD) diet-induced NAFLD in mice. Male C57BL/6 mice (n=21) were divided into three groups (n=7 per group): (1) control fed with standard chow, (2) MCD2 groupfed with MCD diet for 2 weeks, and (3) MCD2+LA group2 weeks on MCD receiving LA i.p. 100mg/kg/day. After the treatment, liver samples were taken for pathohistology, oxidative stress parameters, antioxidative enzymes, and liver free fatty acid (FFA) composition. Mild microvesicular hepatic steatosis was found in MCD2 group, while it was reduced to single fat droplets evident in MCD2+LA group. Lipid peroxidation and nitrosative stress were increased by MCD diet, while LA administration induced a decrease in liver malondialdehyde and nitrates+nitrites level. Similary, LA improved liver antioxidative capacity by increasing total superoxide dismutase (tSOD), manganese SOD (MnSOD), and copper/zinc-SOD (Cu/ZnSOD) activity as well as glutathione (GSH) content. Liver FFA profile has shown a significant decrease in saturated acids, arachidonic, and docosahexaenoic acid (DHA), while LA treatment increased their proportions. It can be concluded that LA ameliorates lipid peroxidation and nitrosative stress in MCD diet-induced hepatic steatosis through an increase in SOD activity and GSH level. In addition, LA increases the proportion of palmitic, stearic, arachidonic, and DHA in the fatty liver. An increase in DHA may be a potential mechanism of anti-inflammatory and antioxidant effects of LA in MCD diet-induced NAFLD.
PB  - Mary Ann Liebert, Inc, New Rochelle
T2  - Journal of Medicinal Food
T1  - The Effects of alpha-Lipoic Acid on Liver Oxidative Stress and Free Fatty Acid Composition in Methionine-Choline Deficient Diet-Induced NAFLD
VL  - 17
IS  - 2
SP  - 254
EP  - 261
DO  - 10.1089/jmf.2013.0111
ER  - 
@article{
author = "Stanković, Milena N. and Mladenović, Dušan and Ninković, Milica and Đuričić, Ivana and Šobajić, Slađana and Jorgacević, Bojan and de Luka, Silvio and Jesić-Vukicević, Rada and Radosavljević, Tatjana S.",
year = "2014",
abstract = "Development of nonalcoholic fatty liver disease (NAFLD) occurs through initial steatosis and subsequent oxidative stress. The aim of this study was to examine the effects of -lipoic acid (LA) on methionine-choline deficient (MCD) diet-induced NAFLD in mice. Male C57BL/6 mice (n=21) were divided into three groups (n=7 per group): (1) control fed with standard chow, (2) MCD2 groupfed with MCD diet for 2 weeks, and (3) MCD2+LA group2 weeks on MCD receiving LA i.p. 100mg/kg/day. After the treatment, liver samples were taken for pathohistology, oxidative stress parameters, antioxidative enzymes, and liver free fatty acid (FFA) composition. Mild microvesicular hepatic steatosis was found in MCD2 group, while it was reduced to single fat droplets evident in MCD2+LA group. Lipid peroxidation and nitrosative stress were increased by MCD diet, while LA administration induced a decrease in liver malondialdehyde and nitrates+nitrites level. Similary, LA improved liver antioxidative capacity by increasing total superoxide dismutase (tSOD), manganese SOD (MnSOD), and copper/zinc-SOD (Cu/ZnSOD) activity as well as glutathione (GSH) content. Liver FFA profile has shown a significant decrease in saturated acids, arachidonic, and docosahexaenoic acid (DHA), while LA treatment increased their proportions. It can be concluded that LA ameliorates lipid peroxidation and nitrosative stress in MCD diet-induced hepatic steatosis through an increase in SOD activity and GSH level. In addition, LA increases the proportion of palmitic, stearic, arachidonic, and DHA in the fatty liver. An increase in DHA may be a potential mechanism of anti-inflammatory and antioxidant effects of LA in MCD diet-induced NAFLD.",
publisher = "Mary Ann Liebert, Inc, New Rochelle",
journal = "Journal of Medicinal Food",
title = "The Effects of alpha-Lipoic Acid on Liver Oxidative Stress and Free Fatty Acid Composition in Methionine-Choline Deficient Diet-Induced NAFLD",
volume = "17",
number = "2",
pages = "254-261",
doi = "10.1089/jmf.2013.0111"
}
Stanković, M. N., Mladenović, D., Ninković, M., Đuričić, I., Šobajić, S., Jorgacević, B., de Luka, S., Jesić-Vukicević, R.,& Radosavljević, T. S.. (2014). The Effects of alpha-Lipoic Acid on Liver Oxidative Stress and Free Fatty Acid Composition in Methionine-Choline Deficient Diet-Induced NAFLD. in Journal of Medicinal Food
Mary Ann Liebert, Inc, New Rochelle., 17(2), 254-261.
https://doi.org/10.1089/jmf.2013.0111
Stanković MN, Mladenović D, Ninković M, Đuričić I, Šobajić S, Jorgacević B, de Luka S, Jesić-Vukicević R, Radosavljević TS. The Effects of alpha-Lipoic Acid on Liver Oxidative Stress and Free Fatty Acid Composition in Methionine-Choline Deficient Diet-Induced NAFLD. in Journal of Medicinal Food. 2014;17(2):254-261.
doi:10.1089/jmf.2013.0111 .
Stanković, Milena N., Mladenović, Dušan, Ninković, Milica, Đuričić, Ivana, Šobajić, Slađana, Jorgacević, Bojan, de Luka, Silvio, Jesić-Vukicević, Rada, Radosavljević, Tatjana S., "The Effects of alpha-Lipoic Acid on Liver Oxidative Stress and Free Fatty Acid Composition in Methionine-Choline Deficient Diet-Induced NAFLD" in Journal of Medicinal Food, 17, no. 2 (2014):254-261,
https://doi.org/10.1089/jmf.2013.0111 . .
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Time-dependent Changes and Association Between Liver Free Fatty Acids, Serum Lipid Profile and Histological Features in Mice Model of Nonalcoholic Fatty Liver Disease

Stanković, Milena N.; Mladenović, Dušan; Đuričić, Ivana; Šobajić, Slađana; Timić, Jasmina; Jorgačević, Bojan; Aleksić, Vuk; Vucević, Danijela B.; Jesić-Vukicević, Rada; Radosavljević, Tatjana S.

(Elsevier Science Inc, New York, 2014)

TY  - JOUR
AU  - Stanković, Milena N.
AU  - Mladenović, Dušan
AU  - Đuričić, Ivana
AU  - Šobajić, Slađana
AU  - Timić, Jasmina
AU  - Jorgačević, Bojan
AU  - Aleksić, Vuk
AU  - Vucević, Danijela B.
AU  - Jesić-Vukicević, Rada
AU  - Radosavljević, Tatjana S.
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2153
AB  - Background and Aims. Methionine-choline deficient (MCD) diet duration necessary for development of non-alcoholic fatty liver disease (NAFLD) and the dynamic of lipid profile and fatty acids are not completely established. The study examined dynamics and association between liver free fatty acids (FFA), serum lipid profile and liver morphological changes on MCD diet-induced NAFLD in mice. Methods. Male C57BL/6 mice (n = 28) were divided into four groups (n = 7 per group): control: fed with standard chow, MCD diet-fed groups: 2, 4 or 6 weeks. After treatment, liver and blood samples were taken for histopathology, serum lipid profile, and liver FFA composition. Results. Hepatic FFA profile showed a decrease in saturated acids, arachidonic and docosahexaenoic acid, whereas proportions of docosapentaenoic, oleic and linoleic acid were increased. Total cholesterol, HDL and triglycerides progressively decreased, whereas LDL level progressively increased. Focal fatty change in the liver appeared after 2 weeks, whereas diffuse fatty change with severe inflammation and ballooned hepatocytes were evident after 6 weeks. Conclusions. Six-week diet model may be appropriate for investigation of the role of lipotoxicity in the progression of NAFLD. Therefore, supplementation with n-3 polyunsaturated acid like DHA, rather than DPA, especially in the initial stage of fatty liver disease, may potentially have preventive effects and alleviate development of NAFLD/NASH and may also potentially reduce cardiovascular risk by moderating dyslipidemia.
PB  - Elsevier Science Inc, New York
T2  - Archives of Medical Research
T1  - Time-dependent Changes and Association Between Liver Free Fatty Acids, Serum Lipid Profile and Histological Features in Mice Model of Nonalcoholic Fatty Liver Disease
VL  - 45
IS  - 2
SP  - 116
EP  - 124
DO  - 10.1016/j.arcmed.2013.12.010
ER  - 
@article{
author = "Stanković, Milena N. and Mladenović, Dušan and Đuričić, Ivana and Šobajić, Slađana and Timić, Jasmina and Jorgačević, Bojan and Aleksić, Vuk and Vucević, Danijela B. and Jesić-Vukicević, Rada and Radosavljević, Tatjana S.",
year = "2014",
abstract = "Background and Aims. Methionine-choline deficient (MCD) diet duration necessary for development of non-alcoholic fatty liver disease (NAFLD) and the dynamic of lipid profile and fatty acids are not completely established. The study examined dynamics and association between liver free fatty acids (FFA), serum lipid profile and liver morphological changes on MCD diet-induced NAFLD in mice. Methods. Male C57BL/6 mice (n = 28) were divided into four groups (n = 7 per group): control: fed with standard chow, MCD diet-fed groups: 2, 4 or 6 weeks. After treatment, liver and blood samples were taken for histopathology, serum lipid profile, and liver FFA composition. Results. Hepatic FFA profile showed a decrease in saturated acids, arachidonic and docosahexaenoic acid, whereas proportions of docosapentaenoic, oleic and linoleic acid were increased. Total cholesterol, HDL and triglycerides progressively decreased, whereas LDL level progressively increased. Focal fatty change in the liver appeared after 2 weeks, whereas diffuse fatty change with severe inflammation and ballooned hepatocytes were evident after 6 weeks. Conclusions. Six-week diet model may be appropriate for investigation of the role of lipotoxicity in the progression of NAFLD. Therefore, supplementation with n-3 polyunsaturated acid like DHA, rather than DPA, especially in the initial stage of fatty liver disease, may potentially have preventive effects and alleviate development of NAFLD/NASH and may also potentially reduce cardiovascular risk by moderating dyslipidemia.",
publisher = "Elsevier Science Inc, New York",
journal = "Archives of Medical Research",
title = "Time-dependent Changes and Association Between Liver Free Fatty Acids, Serum Lipid Profile and Histological Features in Mice Model of Nonalcoholic Fatty Liver Disease",
volume = "45",
number = "2",
pages = "116-124",
doi = "10.1016/j.arcmed.2013.12.010"
}
Stanković, M. N., Mladenović, D., Đuričić, I., Šobajić, S., Timić, J., Jorgačević, B., Aleksić, V., Vucević, D. B., Jesić-Vukicević, R.,& Radosavljević, T. S.. (2014). Time-dependent Changes and Association Between Liver Free Fatty Acids, Serum Lipid Profile and Histological Features in Mice Model of Nonalcoholic Fatty Liver Disease. in Archives of Medical Research
Elsevier Science Inc, New York., 45(2), 116-124.
https://doi.org/10.1016/j.arcmed.2013.12.010
Stanković MN, Mladenović D, Đuričić I, Šobajić S, Timić J, Jorgačević B, Aleksić V, Vucević DB, Jesić-Vukicević R, Radosavljević TS. Time-dependent Changes and Association Between Liver Free Fatty Acids, Serum Lipid Profile and Histological Features in Mice Model of Nonalcoholic Fatty Liver Disease. in Archives of Medical Research. 2014;45(2):116-124.
doi:10.1016/j.arcmed.2013.12.010 .
Stanković, Milena N., Mladenović, Dušan, Đuričić, Ivana, Šobajić, Slađana, Timić, Jasmina, Jorgačević, Bojan, Aleksić, Vuk, Vucević, Danijela B., Jesić-Vukicević, Rada, Radosavljević, Tatjana S., "Time-dependent Changes and Association Between Liver Free Fatty Acids, Serum Lipid Profile and Histological Features in Mice Model of Nonalcoholic Fatty Liver Disease" in Archives of Medical Research, 45, no. 2 (2014):116-124,
https://doi.org/10.1016/j.arcmed.2013.12.010 . .
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