Browsing by Author "Djukic, Tatjana (36193753800)"

It is becoming increasingly evident that oxidative stress has a supporting role in pathophysiology and progression of primary open angle glaucoma (POAG). The aim of our study was to assess the association between polymorphisms in genes encoding enzymes involved in redox homeostasis, mitochondrial superoxide dismutase (SOD2), glutathione peroxidase (GPX1) and glutathione transferases (GSTs) with susceptibility to POAG. Single nucleotide polymorphisms in GST omega (GSTO1rs4925, GSTO2 rs156697), pi 1 (GSTP1 rs1695), as well as GPX1 (rs1050450) and SOD2 (rs4880) were determined by quantitative polymerase chain reaction (qPCR) in 102 POAG patients and 302 respective controls. The risk for POAG development was noted in carriers of both GSTO2*GG and GSTO1*AA variant genotypes (OR = 8.21, p = 0.002). Individuals who carried GPX1*TT and SOD2*CC genotypes had also an increased risk of POAG development but without significance after Bonferroni multiple test correction (OR = 6.66, p = 0.005). The present study supports the hypothesis that in combination, GSTO1/GSTO2, modulate the risk of primary open angle glaucoma. © 2021 Elsevier Ltd

It is becoming increasingly evident that oxidative stress has a supporting role in pathophysiology and progression of primary open angle glaucoma (POAG). The aim of our study was to assess the association between polymorphisms in genes encoding enzymes involved in redox homeostasis, mitochondrial superoxide dismutase (SOD2), glutathione peroxidase (GPX1) and glutathione transferases (GSTs) with susceptibility to POAG. Single nucleotide polymorphisms in GST omega (GSTO1rs4925, GSTO2 rs156697), pi 1 (GSTP1 rs1695), as well as GPX1 (rs1050450) and SOD2 (rs4880) were determined by quantitative polymerase chain reaction (qPCR) in 102 POAG patients and 302 respective controls. The risk for POAG development was noted in carriers of both GSTO2*GG and GSTO1*AA variant genotypes (OR = 8.21, p = 0.002). Individuals who carried GPX1*TT and SOD2*CC genotypes had also an increased risk of POAG development but without significance after Bonferroni multiple test correction (OR = 6.66, p = 0.005). The present study supports the hypothesis that in combination, GSTO1/GSTO2, modulate the risk of primary open angle glaucoma. © 2021 Elsevier Ltd

Purpose: To get more insight into molecular mechanisms underlying oxidative stress and its role in different types of seizure, in this study, oxidative byproducts of proteins, lipids and DNA, as well as, antioxidant enzyme activities were studied in adult patients with epilepsy. Methods: Study was performed in 60 patients with epilepsy and in 25 healthy controls. Plasma protein reactive carbonyl derivatives (RCD) and protein thiol groups (P-SH), byproducts of oxidative protein damage, as well as antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), representative byproducts of lipid and DNA oxidative damage, respectively, were determined by enzyme immunoassay. Results: RCD levels were significantly increased (p = 0.001), while P-SH content was decreased in patients with first seizure (p = 0.052) compared to controls, independently of the seizure type. Urinary 8-epi-PGF2α and 8-OHdG were significantly increased in patients with epilepsy (p = 0.001 and p = 0.001). Rise in 8-epi-PGF2α was more pronounced in patients with generalized tonic-clonic seizure (GTCS) compared to those with partial seizure (PS). Both SOD and GPX activity were significantly increased in epileptic patients compared to controls (p = 0.001 and p = 0.001), but only SOD activity was significantly higher in patients with GTCS than in those with PS. Conclusions: Data on enhanced protein, lipid and DNA oxidation, together with upregulated antioxidant enzyme activities, confirm the existence of systemic oxidative stress in patients with epilepsy. It might be speculated that post-translational modification to existing functional proteins, particularly alterations to ion channels, might be at least partially responsible for acute early changes in neuronal networks. © 2010 British Epilepsy Association.

Purpose: To get more insight into molecular mechanisms underlying oxidative stress and its role in different types of seizure, in this study, oxidative byproducts of proteins, lipids and DNA, as well as, antioxidant enzyme activities were studied in adult patients with epilepsy. Methods: Study was performed in 60 patients with epilepsy and in 25 healthy controls. Plasma protein reactive carbonyl derivatives (RCD) and protein thiol groups (P-SH), byproducts of oxidative protein damage, as well as antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), representative byproducts of lipid and DNA oxidative damage, respectively, were determined by enzyme immunoassay. Results: RCD levels were significantly increased (p = 0.001), while P-SH content was decreased in patients with first seizure (p = 0.052) compared to controls, independently of the seizure type. Urinary 8-epi-PGF2α and 8-OHdG were significantly increased in patients with epilepsy (p = 0.001 and p = 0.001). Rise in 8-epi-PGF2α was more pronounced in patients with generalized tonic-clonic seizure (GTCS) compared to those with partial seizure (PS). Both SOD and GPX activity were significantly increased in epileptic patients compared to controls (p = 0.001 and p = 0.001), but only SOD activity was significantly higher in patients with GTCS than in those with PS. Conclusions: Data on enhanced protein, lipid and DNA oxidation, together with upregulated antioxidant enzyme activities, confirm the existence of systemic oxidative stress in patients with epilepsy. It might be speculated that post-translational modification to existing functional proteins, particularly alterations to ion channels, might be at least partially responsible for acute early changes in neuronal networks. © 2010 British Epilepsy Association.

Heart failure (HF) is one of the major cardiovascular causes of death worldwide. In this study, we explored the Effects of folic acid (FA) on cardiometabolic, oxidative stress biomarker changes, and the activity of proliferation marker Ki67 in monocrotaline-induced HF. The research was conducted during a 4 week period using five experimental groups (eight animals per group): Blank solution exposed controls (C1: 1 mL/kg physiological saline, 1 day; C2: 1 mL/kg physiological saline, 28 days), monocrotaline (MCT) induced HF (50 mg/kg MCT), FA (5 mg·kg−1·day−1 FA), and MCT+FA (50 mg/kg MCT, 5 mg·kg−1·day−1 FA). Superoxide dismutase and glutathione peroxidase activities together with total glutathione and parameters of oxidative damage of proteins were determined in cardiac tissue as well as cardiometabolic parameters in plasma or serum. The total glutathionylation was determined by Western blot and proliferation marker Ki67 was assessed by immunohistochemistry. The right ventricular (RV) wall hypertrophy and Ki67 positivity, accompanied by a significant increase of troponin T, has been shown in MCT-induced HF. The antioxidant effect of FA was reflected through superoxide dismutase activity, reduced Ki67 positivity in the RV wall, and a slightly decreased total glutathionylation level. © 2020, Canadian Science Publishing. All rights reserved.

Heart failure (HF) is one of the major cardiovascular causes of death worldwide. In this study, we explored the Effects of folic acid (FA) on cardiometabolic, oxidative stress biomarker changes, and the activity of proliferation marker Ki67 in monocrotaline-induced HF. The research was conducted during a 4 week period using five experimental groups (eight animals per group): Blank solution exposed controls (C1: 1 mL/kg physiological saline, 1 day; C2: 1 mL/kg physiological saline, 28 days), monocrotaline (MCT) induced HF (50 mg/kg MCT), FA (5 mg·kg−1·day−1 FA), and MCT+FA (50 mg/kg MCT, 5 mg·kg−1·day−1 FA). Superoxide dismutase and glutathione peroxidase activities together with total glutathione and parameters of oxidative damage of proteins were determined in cardiac tissue as well as cardiometabolic parameters in plasma or serum. The total glutathionylation was determined by Western blot and proliferation marker Ki67 was assessed by immunohistochemistry. The right ventricular (RV) wall hypertrophy and Ki67 positivity, accompanied by a significant increase of troponin T, has been shown in MCT-induced HF. The antioxidant effect of FA was reflected through superoxide dismutase activity, reduced Ki67 positivity in the RV wall, and a slightly decreased total glutathionylation level. © 2020, Canadian Science Publishing. All rights reserved.

Introduction: It has been supposed that endocrine disturbances might be responsible for PCOS-associated oxidative stress, with special emphasis on hyperandrogenism. Considering the potential relationship between hyperandrogenism and increased free radical production, parameters of oxidative stress were determined in non-obese normoinsulinaemic adolescent girls newly diagnosed with polycystic ovary syndrome (PCOS). Materials and methods: Nitrotyrosin, thiol group concentrations, glutathione peroxidase, and superoxide dismutase activities were determined under fasting conditions and during oral glucose tolerance test (OGTT) in 35 PCOS patients and 17 controls. Insulin resistance was assessed by the homeostasis model (HOMA-IR), HOMA β, IGI, Matsuda insulin sensitivity index (ISI), and AUC for glucose. Glutathione S-transferases (GSTs) polymorphisms were determined by PCR. Results: Under fasting conditions, no significant difference of oxidative stress parameters was found between PCOS and controls. Acute hyperglycaemia during OGTT induced significant alteration in parameters of oxidative protein damage in PCOS patients. Alteration in nitrotyrosin concentrations correlated with testosterone, DHEAS, androstenediones, FAI, and LH, while changes in thiol groups correlated with DHEAS. Significant inverse association was found between LH and ISI, as well as AUC glucose and thiol groups. PCOS girls, carriers of GSTM1-null genotype, had significantly lower testosterone in comparison to ones with GSTM1-active genotype. Conclusions: PCOS girls exhibited high free radical production together with unchanged antioxidant enzymatic capacity, independently from obesity and insulin resistance. Based on associations between oxidative stress parameters and testosterone, DHEAS, and androstenedione, it can be suggested that increased free radical production, probably as a consequence of hyperandrogenaemia, is an early event in the development of PCOS. © 2018 Via Medica.All right reserved.

Introduction: It has been supposed that endocrine disturbances might be responsible for PCOS-associated oxidative stress, with special emphasis on hyperandrogenism. Considering the potential relationship between hyperandrogenism and increased free radical production, parameters of oxidative stress were determined in non-obese normoinsulinaemic adolescent girls newly diagnosed with polycystic ovary syndrome (PCOS). Materials and methods: Nitrotyrosin, thiol group concentrations, glutathione peroxidase, and superoxide dismutase activities were determined under fasting conditions and during oral glucose tolerance test (OGTT) in 35 PCOS patients and 17 controls. Insulin resistance was assessed by the homeostasis model (HOMA-IR), HOMA β, IGI, Matsuda insulin sensitivity index (ISI), and AUC for glucose. Glutathione S-transferases (GSTs) polymorphisms were determined by PCR. Results: Under fasting conditions, no significant difference of oxidative stress parameters was found between PCOS and controls. Acute hyperglycaemia during OGTT induced significant alteration in parameters of oxidative protein damage in PCOS patients. Alteration in nitrotyrosin concentrations correlated with testosterone, DHEAS, androstenediones, FAI, and LH, while changes in thiol groups correlated with DHEAS. Significant inverse association was found between LH and ISI, as well as AUC glucose and thiol groups. PCOS girls, carriers of GSTM1-null genotype, had significantly lower testosterone in comparison to ones with GSTM1-active genotype. Conclusions: PCOS girls exhibited high free radical production together with unchanged antioxidant enzymatic capacity, independently from obesity and insulin resistance. Based on associations between oxidative stress parameters and testosterone, DHEAS, and androstenedione, it can be suggested that increased free radical production, probably as a consequence of hyperandrogenaemia, is an early event in the development of PCOS. © 2018 Via Medica.All right reserved.

BackgroundIncreased oxidative stress is a hallmark of end-stage renal disease (ESRD). Glutathione S-transferases (GST) are involved in the detoxification of xenobiotics and protection of oxidative damage. We hypothesized that genetic polymorphism in antioxidant enzymes GSTA1, GSTM1, GSTP1 and GSTT1 is more frequent in ESRD and modulates the degree of oxidative stress in these patients.MethodsGSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 ESRD patients and 199 age-and gender-matched controls. Markers of protein and lipid oxidative damage [thiol groups, carbonyl groups, advanced oxidative protein products, nitrotyrosine, malondialdehyde (MDA) and MDA adducts], together with total oxidant status and pro-oxidant-antioxidant balance were determined. Results Individual GST polymorphisms influence vulnerability to both protein and lipid oxidation, with GSTM1-null gene variant having the most pronounced effect. Furthermore, a strong combined effect of null/low-activity GSTM1, GSTT1, GSTA1 and GSTP1 genotypes in terms of susceptibility towards oxidative and carbonyl stress was found in ESRD patients. When patients were stratified according to GSTM1 and GSTT1, the highest oxidant damage was noted in those with the GSTM1-null/GSTT1-null genotype. The observed effect was even stronger in patients with the third low-activity GSTP1 or GSTA1 genotype. Finally, the level of oxidative and carbonyl stress was most pronounced in the subgroup of patients with all four null or low-activity GSTM1, GSTT1, GSTP1 and GSTA1 genotypes.ConclusionsAccording to the GST genotype, ESRD patients may be stratified in terms of the level of oxidative and carbonyl stress that might influence cardiovascular prognosis, but could also improve efforts towards individualization of antioxidant treatment. © 2013 The Author.

Disturbed redox balance in heart failure (HF) might contribute to impairment of cardiac function, by oxidative damage, or by regulation of cell signaling. The role of polymorphism in glutathione transferases (GSTs), involved both in antioxidant defense and in regulation of apoptotic signaling pathways in HF, has been proposed. We aimed to determine whether GST genotypes exhibit differential risk effects between coronary artery disease (CAD) and idiopathic dilated cardiomyopathy (IDC) in HF patients. GSTA1, GSTM1, GSTP1, and GSTT1 genotypes were determined in 194 HF patients (109 CAD, 85 IDC) and 274 age- and gender-matched controls. No significant association was found for GSTA1, GSTM1, and GSTT1 genotypes with HF occurrence due to either CAD or IDC. However, carriers of at least one variant GSTP1∗Val (rs1695) allele were at 1.7-fold increased HF risk than GSTP1∗Ile/Ile carriers (p = 0 031), which was higher when combined with the variant GSTA1∗B allele (OR = 2 2, p = 0 034). In HF patients stratified based on the underlying cause of disease, an even stronger association was observed in HF patients due to CAD, who were carriers of a combined GSTP1(rs1695)/GSTA1 “risk-associated” genotype (OR = 2 8, p = 0 033) or a combined GSTP1∗Ile/Val+Val/Val (rs1695)/GSTP1∗AlaVal+∗ValVal (rs1138272) genotype (OR = 2 1, p = 0 056). Moreover, these patients exhibited significantly decreased left ventricular end-systolic diameter compared to GSTA1∗ AA/GSTP1∗IleIle carriers (p = 0 021). Higher values of ICAM-1 were found in carriers of the GSTP1∗IleVal+∗ValVal (rs1695) (p = 0 041) genotype, whereas higher TNFα was determined in carriers of the GSTP1∗AlaVal+∗ValVal genotype (rs1138272) (p = 0 041). In conclusion, GSTP1 polymorphic variants may determine individual susceptibility to oxidative stress, inflammation, and endothelial dysfunction in HF. © 2019 Dejan Simeunovic et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Disturbed redox balance in heart failure (HF) might contribute to impairment of cardiac function, by oxidative damage, or by regulation of cell signaling. The role of polymorphism in glutathione transferases (GSTs), involved both in antioxidant defense and in regulation of apoptotic signaling pathways in HF, has been proposed. We aimed to determine whether GST genotypes exhibit differential risk effects between coronary artery disease (CAD) and idiopathic dilated cardiomyopathy (IDC) in HF patients. GSTA1, GSTM1, GSTP1, and GSTT1 genotypes were determined in 194 HF patients (109 CAD, 85 IDC) and 274 age- and gender-matched controls. No significant association was found for GSTA1, GSTM1, and GSTT1 genotypes with HF occurrence due to either CAD or IDC. However, carriers of at least one variant GSTP1∗Val (rs1695) allele were at 1.7-fold increased HF risk than GSTP1∗Ile/Ile carriers (p = 0 031), which was higher when combined with the variant GSTA1∗B allele (OR = 2 2, p = 0 034). In HF patients stratified based on the underlying cause of disease, an even stronger association was observed in HF patients due to CAD, who were carriers of a combined GSTP1(rs1695)/GSTA1 “risk-associated” genotype (OR = 2 8, p = 0 033) or a combined GSTP1∗Ile/Val+Val/Val (rs1695)/GSTP1∗AlaVal+∗ValVal (rs1138272) genotype (OR = 2 1, p = 0 056). Moreover, these patients exhibited significantly decreased left ventricular end-systolic diameter compared to GSTA1∗ AA/GSTP1∗IleIle carriers (p = 0 021). Higher values of ICAM-1 were found in carriers of the GSTP1∗IleVal+∗ValVal (rs1695) (p = 0 041) genotype, whereas higher TNFα was determined in carriers of the GSTP1∗AlaVal+∗ValVal genotype (rs1138272) (p = 0 041). In conclusion, GSTP1 polymorphic variants may determine individual susceptibility to oxidative stress, inflammation, and endothelial dysfunction in HF. © 2019 Dejan Simeunovic et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objectives: Glutathione S-transferases (GSTs) are a family of enzymes involved in detoxification. Genes encoding for GSTA1, GSTM1, GSTP1, and GSTT1 proteins are polymorphic, which can result in complete or partial loss of enzyme activity. Previous studies have associated polymorphisms of GSTA1, GSTM1, and GSTP1 genes with a higher risk of bladder cancer, but this is still controversial. Potential role of GSTA1 polymorphism in susceptibility to bladder cancer in Whites is lacking. We examined association between GSTA1, GSTM1, GSTP1, and GSTT1 gene variants and bladder cancer risk and evaluated whether they were modified by smoking. Materials and methods: A hospital-based case-control study recruited 201 incidence cases and 122 age-matched controls. Deletion polymorphism of GSTM1 and GSTT1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of GSTA1 and GSTP1 was identified by restriction fragment length polymorphism method. Uniconditional multivariate logistic regression was applied to model association between genetic polymorphisms and bladder cancer risk, as well as effect modification by smoking. Results: No significant difference was observed in the distributions of GSTM1, GSTT1, GSTA1, and GSTP1 gene variants between patients and controls. None of the examined polymorphisms was significantly associated with bladder cancer risk independently. The results of gene-smoking interaction analyses indicated a significant combined effect of smoking and all common GST polymorphisms tested (P for trend = 0.001). However, the most significant effect on bladder cancer risk was observed in smokers carrying lower activity GSTA1-AB/BB and GSTM-null genotype (OR = 3.5, P < 0.05) compared with GSTA1-AA and GSTM1-active non-smokers. Overall, the risk observed did not significantly differ with respect to quantity of cigarettes smoked. However, heavy smokers with GSTM1-null genotype had 2 times higher risk of bladder cancer than GSTM1-null light smokers (OR = 4.8 vs. OR = 2.0) when GSTM1-active non-smokers served as reference group. Smokers carrying both GSTM1-null and GSTA1-AB + BB genotypes exhibited the highest risk of bladder cancer (OR = 2.00, P = 0.123). Conclusions: Null or low-activity genotypes of the GSTA1, GSTM1, GSTT1, and GSTP1 did not contribute independently towards the risk of bladder cancer in our patients. However, in association with smoking, both low activity GSTA1 and GSTM1-null genotype increase individual susceptibility to bladder cancer. © 2013 .

Objectives: To examine the association between gene variants of the detoxifying and antioxidant enzymes glutathione transferase M1 (GSTM1) and glutathione transferase A1 (GSTA1) and the extent of oxidative damage in patients with transitional cell carcinoma (TCC) of the urinary bladder. Methods: GSTM1 deletion polymorphism was identified by polymerase chain reaction, and the restriction fragment length polymorphism method was used for the single nucleotide polymorphism of GSTA1. Enzyme immunoassay was used to determine markers of DNA (8-hydroxy-2′ -deoxyguanosine, 8-OHdG) and lipid (8-epiprostaglandin F2α) oxidative damage in the urine of 80 TCC patients and 60 age-matched controls. Results: Urinary 8-OHdG and 8-epi-prostaglandin F2α concentrations in TCC patients were significantly higher than in controls (p = 0.043 and 0.001, respectively). GSTM1 and GSTA1 polymorphisms influence vulnerability to both DNA and lipid oxidation, with the GSTM1-null gene variant having a more pronounced effect. A significant effect of combined GSTM1 and GSTA1 genotypes on the extent of oxidative damage was found only for 8-OHdG (p = 0.018). In addition, TCC patients with the most malignant tumors exhibited significantly higher frequencies of GSTM1-null or GSTA1-low activity genotypes, associated with a twofold increase in urinary 8-OHdG concentration (p = 0.044). Conclusions: Our results suggest that absent GSTM1 or reduced GSTA1 antioxidant activity may increase the accumulation of oxidative DNA damage, thereby contributing to the malignant potential of TCC. © W.S. Maney & Son Ltd 2013.

Objectives: To examine the association between gene variants of the detoxifying and antioxidant enzymes glutathione transferase M1 (GSTM1) and glutathione transferase A1 (GSTA1) and the extent of oxidative damage in patients with transitional cell carcinoma (TCC) of the urinary bladder. Methods: GSTM1 deletion polymorphism was identified by polymerase chain reaction, and the restriction fragment length polymorphism method was used for the single nucleotide polymorphism of GSTA1. Enzyme immunoassay was used to determine markers of DNA (8-hydroxy-2′ -deoxyguanosine, 8-OHdG) and lipid (8-epiprostaglandin F2α) oxidative damage in the urine of 80 TCC patients and 60 age-matched controls. Results: Urinary 8-OHdG and 8-epi-prostaglandin F2α concentrations in TCC patients were significantly higher than in controls (p = 0.043 and 0.001, respectively). GSTM1 and GSTA1 polymorphisms influence vulnerability to both DNA and lipid oxidation, with the GSTM1-null gene variant having a more pronounced effect. A significant effect of combined GSTM1 and GSTA1 genotypes on the extent of oxidative damage was found only for 8-OHdG (p = 0.018). In addition, TCC patients with the most malignant tumors exhibited significantly higher frequencies of GSTM1-null or GSTA1-low activity genotypes, associated with a twofold increase in urinary 8-OHdG concentration (p = 0.044). Conclusions: Our results suggest that absent GSTM1 or reduced GSTA1 antioxidant activity may increase the accumulation of oxidative DNA damage, thereby contributing to the malignant potential of TCC. © W.S. Maney & Son Ltd 2013.

Aim: To evaluate glutathione transferase theta 1 and mu 1 (GSTT1 and GSTM1) polymorphisms as determinants of primary open angle glaucoma (POAG) risk, independently or in combination with cigarette smoking, hypertension and diabetes mellitus. ● Methods: A case-control study with 102 POAG patients and 202 age and gender-matched controls was carried out. Multiplex-polymerase chain reaction method was used for the analysis of GSTM1 and GSTT1 polymorphisms. The differences between two groups were tested by the t-test or χ2test. Logistic regression analysis was used for assessing the risk for disease development. ● Results: The presence of GSTM1-null genotype did not contribute independently towards the risk of POAG. However, individuals with GSTT1-active genotype were at almost two-fold increased risk to develop glaucoma (P=0.044) which increased up to 4.36 when combined with GSTM1-null carriers (P=0.024). When glutathione transferase (GST) genotypes were analyzed in association with cigarette smoking, hypertension and diabetes, only carriers of GSTT1-active genotype had significantly increased risk of POAG development in comparison with GSTT1-null genotype individuals with no history of smoking, hypertension and diabetes, respectively (OR=3.52, P=0.003; OR=10.02, P<0.001; OR=4.53, P=0.002). ● Conclusion: The results obtained indicate that both GSTM1-null and GSTT1-active genotypes are associated with increased POAG risk among smokers, suggesting potential gene-environment interaction in glaucoma development. © 2018, International Journal of Ophthalmology (c/o Editorial Office). All rights reserved.

Omega class glutathione transferases, GSTO1-1 and GSTO2-2, exhibit different activities involved in regulation of inflammation, apoptosis and redox homeostasis. We investigated the the prognostic significance of GSTO1 (rs4925) and GSTO2 (rs156697 and rs2297235) polymorphisms in clear cell renal cell carcinoma (ccRCC) patients. GSTO1-1 and GSTO2-2 expression and phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ /mammalian target of rapamycin (mTOR) and Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathways in non-tumor and tumor ccRCC tissue, as well as possible association of GSTO1-1 with signaling molecules were also assessed. GSTO genotyping was performed by quantitative PCR in 228 ccRCC patients, while expression and immunoprecipitation were analyzed by Western blot in 30 tissue specimens. Shorter survival in male carriers of GSTO1*C/C wild-type genotype compared to the carriers of at least one variant allele was demonstrated (p = 0.049). GSTO1*C/C genotype independently predicted higher risk of overall mortality among male ccRCC patients (p = 0.037). Increased expression of GSTO1-1 and GSTO2-2 was demonstrated in tumor compared to corresponding non-tumor tissue (p = 0.002, p = 0.007, respectively), while GSTO1 expression was correlated with interleukin-1β (IL-1β)/pro-interleukin-1β (pro-IL-1β) ratio (r = 0.260, p = 0.350). Interaction of GSTO1 with downstream effectors of investigated pathways was shown in ccRCC tumor tissue. This study demonstrated significant prognostic role of GSTO1 polymorphism in ccRCC. Up-regulated GSTO1-1 and GSTO2-2 in tumor tissue might contribute to aberrant ccRCC redox homeostasis. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Omega class glutathione transferases, GSTO1-1 and GSTO2-2, exhibit different activities involved in regulation of inflammation, apoptosis and redox homeostasis. We investigated the the prognostic significance of GSTO1 (rs4925) and GSTO2 (rs156697 and rs2297235) polymorphisms in clear cell renal cell carcinoma (ccRCC) patients. GSTO1-1 and GSTO2-2 expression and phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ /mammalian target of rapamycin (mTOR) and Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathways in non-tumor and tumor ccRCC tissue, as well as possible association of GSTO1-1 with signaling molecules were also assessed. GSTO genotyping was performed by quantitative PCR in 228 ccRCC patients, while expression and immunoprecipitation were analyzed by Western blot in 30 tissue specimens. Shorter survival in male carriers of GSTO1*C/C wild-type genotype compared to the carriers of at least one variant allele was demonstrated (p = 0.049). GSTO1*C/C genotype independently predicted higher risk of overall mortality among male ccRCC patients (p = 0.037). Increased expression of GSTO1-1 and GSTO2-2 was demonstrated in tumor compared to corresponding non-tumor tissue (p = 0.002, p = 0.007, respectively), while GSTO1 expression was correlated with interleukin-1β (IL-1β)/pro-interleukin-1β (pro-IL-1β) ratio (r = 0.260, p = 0.350). Interaction of GSTO1 with downstream effectors of investigated pathways was shown in ccRCC tumor tissue. This study demonstrated significant prognostic role of GSTO1 polymorphism in ccRCC. Up-regulated GSTO1-1 and GSTO2-2 in tumor tissue might contribute to aberrant ccRCC redox homeostasis. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Based on the close relationship between dysregulation of redox homeostasis and immune response in SARS-CoV-2 infection, we proposed a possible modifying role of ACE2 and glutathione transferase omega (GSTO) polymorphisms in the individual propensity towards the development of clinical manifestations in COVID-19. The distribution of polymorphisms in ACE2 (rs4646116), GSTO1 (rs4925) and GSTO2 (rs156697) were assessed in 255 COVID-19 patients and 236 matched healthy individuals, emphasizing their individual and haplotype effects on disease development and severity. Polymorphisms were determined by the appropriate qPCR method. The data obtained showed that individuals carrying variant GSTO1*AA and variant GSTO2*GG genotypes exhibit higher odds of COVID-19 development, contrary to ones carrying referent alleles (p = 0.044, p = 0.002, respectively). These findings are confirmed by haplotype analysis. Carriers of H2 haplotype, comprising GSTO1*A and GSTO2*G variant alleles were at 2-fold increased risk of COVID-19 development (p = 0.002). Although ACE2 (rs4646116) polymorphism did not exhibit a statistically significant effect on COVID19 risk (p = 0.100), the risk of COVID-19 development gradually increased with the presence of each additional risk-associated genotype. Further studies are needed to clarify the specific roles of glutathione transferases omega in innate immune response and vitamin C homeostasis once the SARS-CoV-2 infection is initiated in the host cell. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Background: Although the majority of previous findings unequivocally confirmed the existence of systemic oxidative stress in chronic heart failure (CHF) patients, data on prognostic potential of biomarkers of oxidative lipid and protein damage are limited. We aimed to address the relation of oxidative stress markers to severity and prognosis in CHF secondary to ischemic cardiomyopathy. Methods and Results: Plasma malondialdehyde (MDA), protein thiol groups (P-SH), reactive carbonyl derivatives (RCD), together with glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were determined in 120 CHF patients and 69 healthy controls. Increased lipid peroxidation (MDA) and oxidation of plasma proteins (RCD; P-SH) s well as downregulated GSH-Px activity were found in CHF patients compared with controls. Significant correlation was obtained only for RCD content and remodeling indices (LVEDV: r = 0.469, P =.008; LVESV: r = 0.452; P =.011). Cox regression analysis demonstrated only MDA (HR = 3.33; CI: 1.55-7.12; P =.002) as independent predictor of death, whereas SOD was associated with unstable angina pectoris (HR = 2.09; CI: 1.16-3.78; P =.011). Conclusions: In the course of CHF progression, carbonyl stress is implicated in the LV remodeling. Malondialdehyde level might be a useful parameter for monitoring and planning management of CHF patients. © 2012 Elsevier Inc. All rights reserved.

Introduction: Overall survival of patients with end-stage renal disease (ESRD) remains poor. Oxidative stress is one of the major risk factors associated with mortality in this patient group. As glutathione S-transferases (GST) are well-established antioxidants, we hypothesized that a model including GST gene polymorphisms, oxidative damage byproducts and cell adhesion markers has a prognostic role in ESRD patient survival. Methods: A prospective study of 199 patients with ESRD on haemodialysis was conducted. GST genotype, oxidative stress byproducts and cell adhesion molecules were measured in plasma. Multivariate Cox regression and Kaplan-Meier survival analyses were performed to test the predictive ability of these parameters in the 8-year follow-up period. Results: GSTM1-null genotype was associated with significantly shorter overall (HR 1.6, p = 0.018) and cardiovascular-specific (HR 2.1, p = 0.010) survival. Oxidative stress byproducts (advanced oxidation protein products [AOPP], prooxidant-antioxidant balance [PAB], malondialdehyde [MDA]) and cell adhesion molecules (soluble vascular cell adhesion molecule-1 [sVCAM-1] and soluble intercellular adhesion molecule-1 [sICAM-1]) demonstrated a significant predictive role in terms of overall and cardiovascular survival. When 6 biomarkers (GSTM1 genotype, high AOPP/PAB/MDA/-sVCAM-1/sICAM-1) were combined into a scoring model, a significantly shorter overall and cardiovascular survival was observed for patients with the highest score (p < 0.001). Conclusion: We identified a novel panel of biomarkers that can be utilized in predicting survival in ESRD patients. This biomarker signature could enable better monitoring of patients and stratification into appropriate treatment groups. © 2019 © 2019 S. Karger AG, Basel. Copyright: All rights reserved.