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  - Nagorni-Obradović, Ljudmila
AU  - Francuski, Đorđe
AU  - Ljujić, Mila
AU  - Malić, Živka
AU  - Radojković, Dragica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2771
AB  - Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients.
PB  - Springer/Plenum Publishers, New York
T2  - Biochemical Genetics
T1  - Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency
VL  - 54
IS  - 5
SP  - 746
EP  - 752
DO  - 10.1007/s10528-016-9748-7
ER  - 

@article{
author = "Topić, Aleksandra and Nagorni-Obradović, Ljudmila and Francuski, Đorđe and Ljujić, Mila and Malić, Živka and Radojković, Dragica",
year = "2016",
abstract = "Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients.",
publisher = "Springer/Plenum Publishers, New York",
journal = "Biochemical Genetics",
title = "Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency",
volume = "54",
number = "5",
pages = "746-752",
doi = "10.1007/s10528-016-9748-7"
}

Topić, A., Nagorni-Obradović, L., Francuski, Đ., Ljujić, M., Malić, Ž.,& Radojković, D.. (2016). Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency. in Biochemical Genetics
Springer/Plenum Publishers, New York., 54(5), 746-752.
https://doi.org/10.1007/s10528-016-9748-7

Topić A, Nagorni-Obradović L, Francuski Đ, Ljujić M, Malić Ž, Radojković D. Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency. in Biochemical Genetics. 2016;54(5):746-752.
doi:10.1007/s10528-016-9748-7 .

Topić, Aleksandra, Nagorni-Obradović, Ljudmila, Francuski, Đorđe, Ljujić, Mila, Malić, Živka, Radojković, Dragica, "Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency" in Biochemical Genetics, 54, no. 5 (2016):746-752,
https://doi.org/10.1007/s10528-016-9748-7 . .

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 . .