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Effects of commonly used antidiabetic drugs on antioxidant enzymes and liver function test markers in type 2 diabetes mellitus subjects - pilot study.
Ghadge, A, Harke, S, Khadke, S, Diwan, A, Pankaj, M, Kulkarni, O, Ranjekar, P, Harsulkar, A, Kuvalekar, AA
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2015;(8):500-7
Abstract
OBJECTIVE The present study analyzed the effects of antidiabetic drugs on antioxidant enzymes and liver function test (LFT) markers and their association with homeostatic model assessment of insulin resistance (HOMA-IR) in type 2 diabetic subjects. METHODS We assessed healthy and diabetic subjects (100 each). Diabetic subjects were divided based on treatment with only metformin, metformin in combination with other antidiabetic drugs and insulin in combination with other antidiabetic drugs. LFT markers, antioxidant status and HOMA-IR were assessed in the subjects. RESULTS Superoxide dismutase activity was higher (p<0.01) while catalase activity was lower (p<0.01) in the diabetic subjects as compared to controls. Serum glutamate-pyruvate transaminase (SGPT) (p<0.01) and bilirubin (p<0.05) levels were higher in diabetic male subjects while urea (p<0.05) levels were lower and SGPT (p<0.01) levels were higher in diabetic female subjects. In male subjects consuming only metformin, a positive association between HOMA-IR and insulin (p<0.05) was seen. A positive association between HOMA-IR and glucose (p<0.01), insulin (p<0.01), SOD (p<0.01) and SGPT (p<0.05) was seen in males receiving metformin with other drugs. Interestingly, the female subjects on metformin displayed a positive association between HOMA-IR and insulin (p<0.05) only. A positive association of HOMA-IR with glucose (p<0.01) and insulin (p<0.05) was seen in females on metformin in combination with other anti-diabetic drugs. CONCLUSION The alterations in the antioxidant enzyme activities and liver function tests are dependent upon the gender and glycemic status of subjects while the variations in correlations of HOMA-IR with antioxidant enzymes, liver function tests and inflammatory markers are dependent on type of treatments.
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Association between maternal micronutrient status, oxidative stress, and common genetic variants in antioxidant enzymes at 15 weeks׳ gestation in nulliparous women who subsequently develop preeclampsia.
Mistry, HD, Gill, CA, Kurlak, LO, Seed, PT, Hesketh, JE, Méplan, C, Schomburg, L, Chappell, LC, Morgan, L, Poston, L, et al
Free radical biology & medicine. 2015;:147-55
Abstract
Preeclampsia is a pregnancy-specific condition affecting 2-7% of women and a leading cause of perinatal and maternal morbidity and mortality. Deficiencies of specific micronutrient antioxidant activities associated with copper, selenium, zinc, and manganese have previously been linked to preeclampsia at the time of disease. Our aims were to investigate whether maternal plasma micronutrient concentrations and related antioxidant enzyme activities are altered before preeclampsia onset and to examine the dependence on genetic variations in these antioxidant enzymes. Predisease plasma samples (15±1 weeks׳ gestation) were obtained from women enrolled in the international Screening for Pregnancy Endpoints (SCOPE) study who subsequently developed preeclampsia (n=244) and from age- and BMI-matched normotensive controls (n=472). Micronutrient concentrations were measured by inductively coupled plasma mass spectrometry; associated antioxidant enzyme activities, selenoprotein-P, ceruloplasmin concentration and activity, antioxidant capacity, and markers of oxidative stress were measured by colorimetric assays. Sixty-four tag-single-nucleotide polymorphisms (SNPs) within genes encoding the antioxidant enzymes and selenoprotein-P were genotyped using allele-specific competitive PCR. Plasma copper and ceruloplasmin concentrations were modestly but significantly elevated in women who subsequently developed preeclampsia (both P<0.001) compared to controls (median (IQR), copper, 1957.4 (1787, 2177.5) vs 1850.0 (1663.5, 2051.5) µg/L; ceruloplasmin, 2.5 (1.4, 3.2) vs 2.2 (1.2, 3.0) µg/ml). There were no differences in other micronutrients or enzymes between groups. No relationship was observed between genotype for SNPs and antioxidant enzyme activity. This analysis of a prospective cohort study reports maternal micronutrient concentrations in combination with associated antioxidant enzymes and SNPs in their encoding genes in women at 15 weeks׳ gestation that subsequently developed preeclampsia. The modest elevation in copper may contribute to oxidative stress, later in pregnancy, in those women that go on to develop preeclampsia. The lack of evidence to support the hypothesis that functional SNPs influence antioxidant enzyme activity in pregnant women argues against a role for these genes in the etiology of preeclampsia.
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Reduction of retinopathy of prematurity in extremely low gestational age newborns treated with recombinant human Cu/Zn superoxide dismutase.
Parad, RB, Allred, EN, Rosenfeld, WN, Davis, JM
Neonatology. 2012;(2):139-44
Abstract
BACKGROUND Reactive oxygen species have been implicated in the pathogenesis of retinopathy of prematurity (ROP). Extremely low gestational age (GA) newborns (ELGANs) have the highest risk of ROP and might benefit most from treatment with antioxidants. OBJECTIVES To determine whether recombinant human Cu/Zn superoxide dismutase (rhSOD) decreases the incidence or severity of ROP in ELGANs. METHODS A previous multicenter trial of intratracheal rhSOD for prevention of bronchopulmonary dysplasia randomized 302 preterm infants to receive intratracheal rhSOD or placebo at birth and every 48 h for 1 month. An analysis of the incidence and severity of ROP was performed in ELGANs. RESULTS The risk of ROP increased with decreasing GA. Within the entire cohort, no significant differences in ROP were found in the placebo versus rhSOD groups. Subgroup analysis on infants born at <26 weeks (n = 72) revealed a 22% reduction in ROP from 85% (placebo) to 66% (rhSOD) (p = 0.06). In subjects born at <25 weeks (n = 24), ROP was reduced by 53% from 85% (placebo) to 40% (rhSOD) (p = 0.03). ROP severity above stage 2 was found in 42% of placebo-treated infants but only 25% of rhSOD-treated subjects with ROP. CONCLUSIONS This post hoc analysis suggests that rhSOD reduces the risk of developing ROP in ELGANs, although further studies are required to confirm this observation.
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Multiple superoxide dismutase 1/splicing factor serine alanine 15 variants are associated with the development and progression of diabetic nephropathy: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Genetics study.
Al-Kateb, H, Boright, AP, Mirea, L, Xie, X, Sutradhar, R, Mowjoodi, A, Bharaj, B, Liu, M, Bucksa, JM, Arends, VL, et al
Diabetes. 2008;(1):218-28
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Abstract
BACKGROUND Despite familial clustering of nephropathy and retinopathy severity in type 1 diabetes, few gene variants have been consistently associated with these outcomes. RESEARCH DESIGN AND METHODS We performed an individual-based genetic association study with time to renal and retinal outcomes in 1,362 white probands with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Specifically, we genotyped 1,411 SNPs that capture common variations in 212 candidate genes for long-term complications and analyzed them for association with the time from DCCT baseline to event for renal and retinal outcomes using multivariate Cox proportion hazards models. To address multiple testing and assist interpretation of the results, false discovery rate q values were calculated separately for each outcome. RESULTS We observed association between rs17880135 in the 3' region of superoxide dismutase 1 (SOD1) and the incidence of both severe nephropathy (hazard ratio [HR] 2.62 [95% CI 1.64-4.18], P = 5.6 x 10(-5), q = 0.06) and persistent microalbuminuria (1.82 [1.29-2.57], P = 6.4 x 10(-4), q = 0.46). Sequencing and fine-mapping identified additional SOD1 variants, including rs202446, rs9974610, and rs204732, which were also associated (P < 10(-3)) with persistent microalbuminuria, whereas rs17880135 and rs17881180 were similarly associated with the development of severe nephropathy. Attempts to replicate the findings in three cross-sectional case-control studies produced equivocal results. We observed no striking differences between risk genotypes in serum SOD activity, serum SOD1 mass, or SOD1 mRNA expression in lymphoblastoid cell lines. CONCLUSIONS Multiple variations in SOD1 are significantly associated with persistent microalbuminuria and severe nephropathy in the DCCT/EDIC study.