TY  - JOUR
AU  - Malić, Živka
AU  - Topić, Aleksandra
AU  - Francuski, Đorđe
AU  - Stanković, Marija
AU  - Nagorni-Obradović, Ljudmila
AU  - Marković, Bojan
AU  - Radojković, Dragica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2903
AB  - The genetic and non-genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are still poorly understood. We investigated the potential role of genetic variants of xenobiotic-metabolising enzymes (glutathione-S-transferase M1, GSTM1; glutathione-S-transferase T1, GSTT1; microsomal epoxide hydrolase, mEH), oxidative stress (assessed by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG/creatinine), sex, ageing and smoking habits on susceptibility to development of COPD and its severity in Serbian population. The investigated population consisted of 153 healthy subjects (85 males and 68 females) and 71 patients with COPD (33 males and 38 females). Detection of GSTM1*null, GSTT1*null, mEH Tyr113His and mEH His139Arg gene variants was performed by PCR/RFLP method. Urinary 8-oxodG was determined using HPLC-MS/MS, and expressed as 8-oxodG/creatinine. We revealed that increased urinary 8-oxodG/creatinine and leucocytosis are the strongest independent predictors for COPD development. Increased level of oxidative stress increased the risk for COPD in males [odds ratio (OR), 95% confidence interval (CI): 8.42, 2.26-31.28], more than in females (OR, 95% CI: 3.60, 1.37-9.45). Additionally, independent predictors for COPD were ageing in males (OR, 95% CI: 1.29, 1.12-1.48), while in females they were at least one GSTM1 or GSTT1 gene deletion in combination (OR, 95% CI: 23.67, 2.62-213.46), and increased cumulative cigarette consumption (OR, 95% CI: 1.09, 1.01-1.16). Severity of COPD was associated with the combined effect of low mEH activity phenotype, high level of oxidative stress and heavy smoking. In conclusion, early identification of GSTM1*null or GSTT1*null genotypes in females, low mEH activity phenotype in heavy smokers and monitoring of oxidative stress level can be useful diagnostic and prognostic biomarkers.
PB  - Taylor & Francis Inc, Philadelphia
T2  - COPD-Journal of Chronic Obstructive Pulmonary Disease
T1  - Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults
VL  - 14
IS  - 1
SP  - 95
EP  - 104
DO  - 10.1080/15412555.2016.1199667
ER  - 

@article{
author = "Malić, Živka and Topić, Aleksandra and Francuski, Đorđe and Stanković, Marija and Nagorni-Obradović, Ljudmila and Marković, Bojan and Radojković, Dragica",
year = "2017",
abstract = "The genetic and non-genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are still poorly understood. We investigated the potential role of genetic variants of xenobiotic-metabolising enzymes (glutathione-S-transferase M1, GSTM1; glutathione-S-transferase T1, GSTT1; microsomal epoxide hydrolase, mEH), oxidative stress (assessed by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG/creatinine), sex, ageing and smoking habits on susceptibility to development of COPD and its severity in Serbian population. The investigated population consisted of 153 healthy subjects (85 males and 68 females) and 71 patients with COPD (33 males and 38 females). Detection of GSTM1*null, GSTT1*null, mEH Tyr113His and mEH His139Arg gene variants was performed by PCR/RFLP method. Urinary 8-oxodG was determined using HPLC-MS/MS, and expressed as 8-oxodG/creatinine. We revealed that increased urinary 8-oxodG/creatinine and leucocytosis are the strongest independent predictors for COPD development. Increased level of oxidative stress increased the risk for COPD in males [odds ratio (OR), 95% confidence interval (CI): 8.42, 2.26-31.28], more than in females (OR, 95% CI: 3.60, 1.37-9.45). Additionally, independent predictors for COPD were ageing in males (OR, 95% CI: 1.29, 1.12-1.48), while in females they were at least one GSTM1 or GSTT1 gene deletion in combination (OR, 95% CI: 23.67, 2.62-213.46), and increased cumulative cigarette consumption (OR, 95% CI: 1.09, 1.01-1.16). Severity of COPD was associated with the combined effect of low mEH activity phenotype, high level of oxidative stress and heavy smoking. In conclusion, early identification of GSTM1*null or GSTT1*null genotypes in females, low mEH activity phenotype in heavy smokers and monitoring of oxidative stress level can be useful diagnostic and prognostic biomarkers.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "COPD-Journal of Chronic Obstructive Pulmonary Disease",
title = "Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults",
volume = "14",
number = "1",
pages = "95-104",
doi = "10.1080/15412555.2016.1199667"
}

Malić, Ž., Topić, A., Francuski, Đ., Stanković, M., Nagorni-Obradović, L., Marković, B.,& Radojković, D.. (2017). Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults. in COPD-Journal of Chronic Obstructive Pulmonary Disease
Taylor & Francis Inc, Philadelphia., 14(1), 95-104.
https://doi.org/10.1080/15412555.2016.1199667

Malić Ž, Topić A, Francuski Đ, Stanković M, Nagorni-Obradović L, Marković B, Radojković D. Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults. in COPD-Journal of Chronic Obstructive Pulmonary Disease. 2017;14(1):95-104.
doi:10.1080/15412555.2016.1199667 .

Malić, Živka, Topić, Aleksandra, Francuski, Đorđe, Stanković, Marija, Nagorni-Obradović, Ljudmila, Marković, Bojan, Radojković, Dragica, "Oxidative Stress and Genetic Variants of Xenobiotic-Metabolising Enzymes Associated with COPD Development and Severity in Serbian Adults" in COPD-Journal of Chronic Obstructive Pulmonary Disease, 14, no. 1 (2017):95-104,
https://doi.org/10.1080/15412555.2016.1199667 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Malić, Živka
AU  - Francuski, Đorđe
AU  - Stanković, Marija
AU  - Marković, Bojan
AU  - Soskić, Blagoje
AU  - Tomić, Branko
AU  - Ilić, Stefan
AU  - Dobrivojević, Snežana
AU  - Drca, Sanja
AU  - Radojković, Dragica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2600
AB  - Gender-related differences in the association between polymorphism of xenobiotic-metabolising enzymes or non-genetic biomarkers and susceptibility to oxidative stress was assessed in healthy middle-aged Serbian adults, by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG/creatinine) and total antioxidant status in serum (TAOS). Females were more susceptible to oxidative stress. In both genders, positive predictor of the antioxidative protection was serum triglyceride, while BMI  lt 25 kg/m(2) was associated with oxidative stress. Susceptibility to oxidative stress in males was associated with GSTT1*null allele and increased serum iron, but in females, it was decreased serum bilirubin. Early identification of the risk factors could be important in the prevention of oxidative stress-related diseases.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Biomarkers
T1  - Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults
VL  - 21
IS  - 2
SP  - 186
EP  - 193
DO  - 10.3109/1354750X.2015.1126647
ER  - 

@article{
author = "Topić, Aleksandra and Malić, Živka and Francuski, Đorđe and Stanković, Marija and Marković, Bojan and Soskić, Blagoje and Tomić, Branko and Ilić, Stefan and Dobrivojević, Snežana and Drca, Sanja and Radojković, Dragica",
year = "2016",
abstract = "Gender-related differences in the association between polymorphism of xenobiotic-metabolising enzymes or non-genetic biomarkers and susceptibility to oxidative stress was assessed in healthy middle-aged Serbian adults, by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG/creatinine) and total antioxidant status in serum (TAOS). Females were more susceptible to oxidative stress. In both genders, positive predictor of the antioxidative protection was serum triglyceride, while BMI  lt 25 kg/m(2) was associated with oxidative stress. Susceptibility to oxidative stress in males was associated with GSTT1*null allele and increased serum iron, but in females, it was decreased serum bilirubin. Early identification of the risk factors could be important in the prevention of oxidative stress-related diseases.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Biomarkers",
title = "Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults",
volume = "21",
number = "2",
pages = "186-193",
doi = "10.3109/1354750X.2015.1126647"
}

Topić, A., Malić, Ž., Francuski, Đ., Stanković, M., Marković, B., Soskić, B., Tomić, B., Ilić, S., Dobrivojević, S., Drca, S.,& Radojković, D.. (2016). Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults. in Biomarkers
Taylor & Francis Ltd, Abingdon., 21(2), 186-193.
https://doi.org/10.3109/1354750X.2015.1126647

Topić A, Malić Ž, Francuski Đ, Stanković M, Marković B, Soskić B, Tomić B, Ilić S, Dobrivojević S, Drca S, Radojković D. Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults. in Biomarkers. 2016;21(2):186-193.
doi:10.3109/1354750X.2015.1126647 .

Topić, Aleksandra, Malić, Živka, Francuski, Đorđe, Stanković, Marija, Marković, Bojan, Soskić, Blagoje, Tomić, Branko, Ilić, Stefan, Dobrivojević, Snežana, Drca, Sanja, Radojković, Dragica, "Gender-related differences in susceptibility to oxidative stress in healthy middle-aged Serbian adults" in Biomarkers, 21, no. 2 (2016):186-193,
https://doi.org/10.3109/1354750X.2015.1126647 . .

TY  - JOUR
AU  - Topić, Aleksandra
AU  - Francuski, Đorđe
AU  - Marković, Bojan
AU  - Stanković, Marija
AU  - Dobrivojević, Snežana
AU  - Drca, Sanja
AU  - Radojković, Dragica
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1917
AB  - Objectives: Although there are many nucleobase modifications, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is one of the dominant form of oxidative modifications of DNA. Urinary 8-oxodG is potentially the best non-invasive biomarker of oxidative stress. Defining reference interval for urinary 8-oxodG is a prerequisite for its clinical use as biomarker. Design and methods: Reference population included 229 healthy Serbian adults (130 males and 99 females). The spot urinary 8-oxodG was determined using high performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Urinary creatinine was measured by the kinetic Jaffe method. Results: Analytical performances of the HPLC-MS/MS: CVs within and between-run variations were 5.6% and 2.6%; LOD and LOQ were 1.65 nmol/L and 330 nmol/L; mean recovery and relative accuracy were 96% and 97%. Creatinine level was higher in males than in females, but no gender difference in 8-oxodG level was observed. Upon the adjustment of 8-oxodG to creatinine (8-oxodG/creatinine), higher values were obtained in females (1.38 +/- 0.65 nmol/mmol) than in males (1.05 +/- 0.48 nmol/mmol). Distribution of 8-oxodG/creatinine in spot urine sample was log-normal and gender-related reference intervals (estimated as the 2.5th-97.5th percentiles) were 0.45-2.22 nmol/mmol for males, and 0.54-3.11 nmol/mmol for females. Body mass index (BMI) affects excretion of the 8-oxodG in males, independently of urinary creatinine, while in females it does not. Therefore, BMI might contribute to the gender-related differences of 8-oxodG/creatinine in spot urine samples. Conclusions: This is the first established gender-related reference intervals of spot urinary 8-oxodG/creatinine. Our results contribute to the full validation of 8-oxodG as biomarker of oxidative stress.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Clinical Biochemistry
T1  - Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population
VL  - 46
IS  - 4-5
SP  - 321
EP  - 326
DO  - 10.1016/j.clinbiochem.2012.12.008
ER  - 

@article{
author = "Topić, Aleksandra and Francuski, Đorđe and Marković, Bojan and Stanković, Marija and Dobrivojević, Snežana and Drca, Sanja and Radojković, Dragica",
year = "2013",
abstract = "Objectives: Although there are many nucleobase modifications, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is one of the dominant form of oxidative modifications of DNA. Urinary 8-oxodG is potentially the best non-invasive biomarker of oxidative stress. Defining reference interval for urinary 8-oxodG is a prerequisite for its clinical use as biomarker. Design and methods: Reference population included 229 healthy Serbian adults (130 males and 99 females). The spot urinary 8-oxodG was determined using high performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Urinary creatinine was measured by the kinetic Jaffe method. Results: Analytical performances of the HPLC-MS/MS: CVs within and between-run variations were 5.6% and 2.6%; LOD and LOQ were 1.65 nmol/L and 330 nmol/L; mean recovery and relative accuracy were 96% and 97%. Creatinine level was higher in males than in females, but no gender difference in 8-oxodG level was observed. Upon the adjustment of 8-oxodG to creatinine (8-oxodG/creatinine), higher values were obtained in females (1.38 +/- 0.65 nmol/mmol) than in males (1.05 +/- 0.48 nmol/mmol). Distribution of 8-oxodG/creatinine in spot urine sample was log-normal and gender-related reference intervals (estimated as the 2.5th-97.5th percentiles) were 0.45-2.22 nmol/mmol for males, and 0.54-3.11 nmol/mmol for females. Body mass index (BMI) affects excretion of the 8-oxodG in males, independently of urinary creatinine, while in females it does not. Therefore, BMI might contribute to the gender-related differences of 8-oxodG/creatinine in spot urine samples. Conclusions: This is the first established gender-related reference intervals of spot urinary 8-oxodG/creatinine. Our results contribute to the full validation of 8-oxodG as biomarker of oxidative stress.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Clinical Biochemistry",
title = "Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population",
volume = "46",
number = "4-5",
pages = "321-326",
doi = "10.1016/j.clinbiochem.2012.12.008"
}

Topić, A., Francuski, Đ., Marković, B., Stanković, M., Dobrivojević, S., Drca, S.,& Radojković, D.. (2013). Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population. in Clinical Biochemistry
Pergamon-Elsevier Science Ltd, Oxford., 46(4-5), 321-326.
https://doi.org/10.1016/j.clinbiochem.2012.12.008

Topić A, Francuski Đ, Marković B, Stanković M, Dobrivojević S, Drca S, Radojković D. Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population. in Clinical Biochemistry. 2013;46(4-5):321-326.
doi:10.1016/j.clinbiochem.2012.12.008 .

Topić, Aleksandra, Francuski, Đorđe, Marković, Bojan, Stanković, Marija, Dobrivojević, Snežana, Drca, Sanja, Radojković, Dragica, "Gender-related reference intervals of urinary 8-oxo-7,8-dihydro-2 '-deoxyguanosine determined by liquid chromatography-tandem mass spectrometry in Serbian population" in Clinical Biochemistry, 46, no. 4-5 (2013):321-326,
https://doi.org/10.1016/j.clinbiochem.2012.12.008 . .