Aerobic and anaerobic training effects on the antioxidant enzymes of the blood.

The purpose of the present study was to investigate the effects of aerobic and anaerobic training on serum lipid peroxidation levels and on antioxidant enzyme activities. Long distance runners for aerobic training group, and wrestlers for anaerobic training group were chosen. Non-sporting men were used as control group. When the aerobic power was compared; indirect VO2max of long-distance runners were found higher than wrestlers and control group (p<0.001, p<0.001). When lipid peroxidation levels were compared; levels of the thiobarbituric acid reactive substances (TBARS) of long distance runners were found to be lower than those in the control group (p<0.05), but similar to those found in wrestlers. Comparison of antioxidant enzyme activities in erythrocytes show that there were no significant difference among the groups in superoxide dismutase enzyme activities, but glutathione peroxidase (GPx) activity of long distance runners was higher than that measured in wrestlers (p<0.05). These results suggest that aerobic training increased in erythrocytes GPx activity with a subsequent decrease in plasma TBARS levels but anaerobic training had no effect on this process.     

Manganese superoxide dismutase dimorphism relationship with severity and prognosis in cardiogenic shock due to dilated cardiomyopathy

The aim was to determine (a) Ala-16Val-SOD2 dimorphisms; (b) allelic frequency and phenotype of a common Pro-Leu polymorphism in GPx1, in a cohort of patients with a cardiogenic shock (CS) due to dilated cardiomyopathy without acute coronary syndrome. Consecutive patients with de novo CS that worsened a dilated (DCM) or ischemic (ICM) cardiomyopathy. Congenital heart disease, pacemaker and other shock aetiologies were excluded. To determine oxidative stress (OS), this study evaluated lipid peroxidation, protein oxidation and erythrocyte GPx, SOD and catalase activities. Ala16Val-SOD2 (dbSNP: rs4880) and Pro198Leu-GPx1 (dbSNP: rs1050450) polymorphisms were studied by allelic discrimination using fluorogenic probes and the 5'nuclease (TaqMan) assay. Twenty-four patients (with ICM (n = 8) or DCM (n = 16), age = 57.5 ± 10.7 years, LVEF = 25.3 ± 8.5%, NT-proBNP levels = 8540 ± 1703 ng/L) were included during a 15 month follow-up. OS parameters were significantly higher in patients than in controls. Distribution of MnSOD genotypes was 47% Val/Val-variant, 29.5% Ala/Val and 23.5% Ala/Ala-variants. Severity of CS was more important in patients with Val/Val-variant and can be put in parallel with NT-proBNP levels (Val/Val-variant: 11 310 ± 3875 ng/L vs Ala/Ala-variant: 6486 ± 1375 ng/L and Ala/Val-variant: 6004 ± 2228 ng/L; p < 0.05) and hemodynamic support duration (144.6 vs Ala/Val-variant: 108.8 h and Ala/Ala-variant: 52.5 h; p < 0.05) with a positive correlation (Spearman rho = 0.72, p < 0.05). Moreover, Val/Val-variant significantly influenced the mortality (Spearman rho = 0.67, p < 0.05), but not the morbidity (p = 0.3). Distribution of GPx genotypes was 64% Pro/Pro, 18% Pro/Leu and 18% Leu/Leu. GPx-variants influenced neither GPx activities nor cardiac events. In conclusion, CS was associated with markers of increased OS. GPx polymorphism did not influence the GPx activity. Only the Val-encoding MnSOD allele was significantly correlated with the severity and prognosis of CS.     

Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease

The presence and progression of numerous diseases have been linked to deficiencies in antioxidant systems. The relationships between single nucleotide polymorphisms (SNPs) arising from specific antioxidant enzymes and diseases associated with elevated oxidative stress have been studied with the rationale that they may be useful in screening for diseases. The purpose of this narrative review is to analyse evidence from these studies. The antioxidant enzyme SNPs selected for analysis are based on those most frequently investigated in relation to diseases in humans: superoxide dismutase (SOD2) Ala16Val (80 studies), glutathione peroxidise (GPx1) Pro197Leu (24 studies) and catalase C-262T (22 studies). Although the majority of evidence supports associations between the SOD2 Ala16Val SNP and diseases such as breast, prostate and lung cancers, diabetes and cardiovascular disease, the presence of the SOD2 Ala16Val SNP confers only a small, clinically insignificant reduction (if any) in the risk of these diseases. Other diseases such as bladder cancer, liver disease, nervous system pathologies and asthma have not been consistently related to this SOD SNP genotype. The GPx1 Pro197Leu and catalase C-262T SNP genotypes have been associated with breast cancer, but only in a small number of studies. Thus, currently available evidence suggests antioxidant enzyme SNP genotypes are not useful for screening for diseases in humans.     

SOD2 gene polymorphism and muscle damage markers in elite athletes

Abstract

Exercise-induced oxidative stress is a state that primarily occurs in athletes involved in high-intensity sports when pro-oxidants overwhelm the antioxidant defense system to oxidize proteins, lipids, and nucleic acids. During exercise, oxidative stress is linked to muscle metabolism and muscle damage, because exercise increases free radical production. The T allele of the Ala16Val (rs4880 C/T) polymorphism in the mitochondrial superoxide dismutase 2 (SOD2) gene has been reported to reduce SOD2 efficiency against oxidative stress. In the present study we tested the hypothesis that the SOD2 TT genotype would be underrepresented in elite athletes involved in high-intensity sports and associated with increased values of muscle and liver damage biomarkers. The study involved 2664 Caucasian (2262 Russian and 402 Polish) athletes. SOD2 genotype and allele frequencies were compared to 917 controls. Muscle and liver damage markers [creatine kinase (CK), creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP)] were examined in serum from 1444 Russian athletes. The frequency of the SOD2 TT genotype (18.6%) was significantly lower in power/strength athletes (n = 524) compared to controls (25.0%, p = 0.0076) or athletes involved in low-intensity sports (n = 180; 33.9%, p < 0.0001). Furthermore, the SOD2 T allele was significantly associated with increased activity of CK (females: p = 0.0144) and creatinine level (females: p = 0.0276; males: p = 0.0135) in athletes. Our data show that the SOD2 TT genotype might be unfavorable for high-intensity athletic events.     

Impact of the Superoxide Dismutase 2 Val16Ala Polymorphism on the Relationship between Valproic Acid Exposure and Elevation of γ-Glutamyltransferase in Patients with Epilepsy: A Population Pharmacokinetic-Pharmacodynamic Analysis

Background

There has been accumulating evidence that there are associations among γ-glutamyltransferase (γ-GT) elevation and all-cause mortality, cardiovascular diseases and metabolic diseases, including nonalcoholic fatty liver disease. The primary objective of this study was to evaluate the impact of the most common and potentially functional polymorphisms of antioxidant enzyme genes, i.e. superoxide dismutase 2 (SOD2), glutathione S-transferase M1 and glutathione S-transferase T1, on the γ-GT elevation during valproic acid (VPA) therapy.

Methods and Findings

This retrospective study included 237 and 169 VPA-treated Japanese patients with epilepsy for population pharmacokinetic and pharmacokinetic-pharmacodynamic analyses, respectively. A nonlinear mixed-effect model represented the pharmacokinetics of VPA and the relationships between VPA exposure and γ-GT elevation. A one-compartment model of the pharmacokinetic parameters of VPA adequately described the data; while the model for the probability of the γ-GT elevation was fitted using a logistic regression model, in which the logit function of the probability was a linear function of VPA exposure. The SOD2 Val16Ala polymorphism and complication with intellectual disability were found to be significant covariates influencing the intercept of the logit function for the probability of an elevated γ-GT level. The predicted mean percentages of the subjects with γ-GT elevation were about 2- to 3-fold, 3- to 4-fold and 4- to 8-fold greater in patients with the SOD2 Val/Val genotype but without any intellectual disability, those with the SOD2 Val/Ala or Ala/Ala genotype and intellectual disability and those with the SOD2 Val/Val genotype and intellectual disability, respectively, compared to those with the SOD2 Val/Ala or Ala/Ala genotype without intellectual disability.

Conclusion

Our results showed that the SOD2 Val16Ala polymorphism has an impact on the relationship between VPA exposure and γ-GT elevation in patients with epilepsy. These results suggest that determining the SOD2 genotype could be helpful for preventing the VPA-induced γ-GT elevation.     

Effect of Zinc Supplementation on Antioxidant Activity in Young Wrestlers

This study aims to examine the effect of zinc supplementation on free-radical formation and antioxidant system in individuals who are actively engaged in wrestling as a sport. The study registered a total of 40 male subjects, of whom 20 were wrestlers and 20 were sedentary individuals. The subjects were equally allocated to four groups: group 1, zinc-supplemented sportsmen group; group 2, sportsmen group without supplementation; group 3, zinc-supplemented sedentary group; group 4, sedentary group without supplementation. Blood samples were collected from all subjects twice, once at the beginning of the study and once again at the end of 8-week procedures. The blood samples collected were analyzed to determine the levels of malondialdehyde (MDA), serum glutathione (GSH), serum glutathione peroxidase (GPx) activity, serum superoxide dismutase (SOD) activity (ELISA colorimetric method) and zinc (colorimetric method). No difference was found between MDA levels of the study groups in the beginning of the study. The highest MDA value at the end of the study was obtained in group 4 (p < 0.01). MDA levels in group 2 were established to be significantly higher than those in groups 1 and 3 (p < 0.01). GSH level, GPx, and SOD activities and zinc level measured in the beginning of the study were not different between groups. Measurements performed at the end of the study showed that groups 1 and 3 (zinc-supplemented groups) had the highest GSH level, GPx, and SOD activities and zinc level (p < 0.01). These parameters were not different in the groups without supplementation (groups 2 and 4). Results obtained at the end of the study indicate that zinc supplementation prevents production of free radicals by activating the antioxidant system. In conclusion, physiologic doses of zinc supplementation to athletes may beneficially contribute to their health and performance.     

The association between oxidative stress and obstructive lung impairment in patients with COPD

An oxidant/antioxidant imbalance is thought to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We hypothesized that antioxidant capacity reflected by erythrocyte glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities, and serum levels of the lipid peroxidation product malondialdehyde (MDA), may be related to the severity of obstructive lung impairment in patients with COPD. Erythrocyte GPx, SOD and CAT activities, and serum levels of MDA were measured in 79 consecutive patients with stable COPD. Pulmonary functional tests were assessed by body plethysmography. Moderate COPD (FEV1 50-80%) was present in 23, and severe COPD (FEV1 < 50%) in 56 patients. Erythrocyte GPx activity was significantly lower, and serum MDA levels were significantly higher in patients with severe COPD compared to patients with moderate COPD (GPx: 43.1+/-1.5 vs. 47.7+/-2.9 U/gHb, p<0.05, MDA: 2.4+/-0.1 vs. 2.1+/-0.1 nmol/ml, p<0.05). Linear regression analysis revealed a significant direct relationship between FEV1 and erythrocyte GPx activity (r = 0.234, p<0.05), and a significant inverse relationship between FEV1 and serum MDA levels (r = -0.239, p<0.05). However, no differences were observed in the erythrocyte SOD and CAT activities between the two groups of patients with different severity of COPD. Findings of the present study suggest that antioxidant capacity reflected by erythrocyte GPx activity and serum levels of the lipid peroxidation product MDA are linked to the severity of COPD.     

Effect of nocturnal melatonin intake on cellular damage and recovery from repeated sprint performance during an intensive training schedule

ABSTRACT

An optimal recovery between training sessions is of similar if not greater importance as the training content and program of the training, itself. One of the most used strategies for improving recovery is the ingestion of supplements. The present study aimed to evaluate the effect of 5 mg oral melatonin supplementation on the recovery from repeated sprint (RSA) of performance and biochemical responses (i.e. oxidative stress, leukocytosis cellular damage) after an intensive training camp (TC). Twenty soccer players performed an RSA test before and after an intensive six-day TC associated with nocturnal melatonin (n = 10) or placebo (n = 10) ingestion. Resting and post-RSA test blood samples were obtained before and after the TC. Compared to placebo, melatonin intake decreased resting oxidative stress markers (i.e, advanced oxidation protein products), leukocytosis (i.e. white blood cells (WBC), neutrophils (NE)) and biomarkers of cellular damage (i.e. creatine kinase (CK)). It also lowered post-exercise leukocytosis (i.e. WBC, NE, lymphocytes (LY), monocytes (MO)) and biomarkers of cellular damage (i.e. CK, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT)) and raised the activity of the main antioxidant enzymes (i.e. glutathione peroxidase (GPx), glutathione reductase (GR)). In addition, compared to placebo, melatonin reduced the deterioration of the best and total time during the RSA test after the TC. In conclusion, nocturnal melatonin supplementation during an intensive TC alleviated oxidative stress, leukocytosis and cellular damage and improved recovery of RSA performance in soccer players.     

Fluidity and oxidative stress in erythrocytes from very low birth weight infants during their first 7 days of life

Objective: To study the evolution of lipid peroxidation, enzymatic antioxidants response, lipid profile and membrane fluidity in erythrocytes from very low birth weight (VLBW) infants during their first 7 days of extra-uterine life.

Study design: One hundred and twenty infants were selected and divided in two groups according to their weight and gestational age. Hydroperoxides, fatty-acid profile, fluidity (DPH and TMA-DPH) and catalase, SOD and GPx activities were measured in erythrocytes.

Results: VLBW group showed higher concentration of hydroperoxides and lower membrane fluidity during the first 72 h, lower SOD activity during the first 3 h and higher GPx activity during the first 7 days of life. Also, this group showed lower n-3 polyunsaturated fatty-acids percentage with respect to the term group.

Conclusion: Erythrocytes from VLBW infants showed higher oxidative damage and lower fluidity in their membranes, at least during the first 3 days of extra-uterine life, which may cause alterations in their functions and flexibility.     

Increased prevalence of MnSOD genetic polymorphism in endurance and power athletes

Abstract

The purpose of the current study was to determine the frequency distribution of manganese superoxide dismutase (MnSOD) Val-9Ala polymorphism (rs1799725) among 195 trained endurance and power athletes and 240 healthy controls. Genomic DNA was extracted using a standard protocol. Genotyping of the MnSOD Val-9Ala polymorphism was performed using polymerase chain reaction (PCR). Results showed a higher proportion of the Val/Ala and Ala/Ala genotype, and a lower proportion of Val/Val genotype, in the athletes group compared with that of the controls. The Ala allele frequency was significantly higher (p < 0.001) in the athletes group (46%) compared with that in the control (29%). Interestingly, there was no difference between the endurance and power athletes. In addition, the frequency of Ala/Ala genotype was significantly higher (p < 0.05) among top (international and Olympic-level) athletes (29%) compared with that among national-level endurance and power athletes (17%). We conclude that 1) the Ala allele is more frequent in athletes than in controls; and 2) the higher frequency of the Ala allele was noted in both endurance and power athletes compared with that in controls, suggesting that the positive association between the Ala allele and athletic performance may be related to ROS-related angiogenesis, mitochondrial biosynthesis, and muscle hypertrophy, and not to MnSOD aerobic properties.     

The effects of long-term low intensity aerobic training and detraining on serum lipid and lipoprotein concentrations in elderly men and women

The effects of long-term low intensity aerobic training and detraining on serum lipid and lipoprotein concentrations were examined in 30 elderly men and women. These subjects were randomly divided into two groups. The training group [n=15; 7 men and 8 women; mean age 75.5 (SD 5.6) years] agreed to take part in physical training using a treadmill with an exercise intensity at the blood lactate concentration threshold for 30 min 3–6 times a week for 9 months. The other group [n=15; 7 men and 8 women; mean age 73.7 (SD 4.4) years] did not perform any particular physical training and was followed as the control. Following this training period the high density lipoprotein-cholesterol (HDL-C) had increased significantly (P<0.01) while the total cholesterol (TC) : HDL-C ratio had decreased significantly (P<0.01) in the training group after 9 months but had not changed in the control group. The TC, triglyceride (TG) and low density lipoprotein-cholesterol (LDL-C) had not changed significantly in either group. No significant difference was seen between the groups throughout the period for TC, LDLC or TG. There was, however, a significant correlation between the initial TC:HDL-C ratio and the change in the TC:HDL-C ratio following 3 months of training (P <0.05). After 1 month of detraining in 5 patients, the HDL-C had decreased significantly (P < 0.05) while the TC:HDL-C had increased significantly in the training group (P<0.01). These results suggested that long-term low intensity aerobic training improved the profile of serum lipid and lipoprotein concentrations, while detraining returned the profile to that of the pretraining levels in elderly persons.     

Polymorphism in the manganese superoxide dismutase gene

Oxidative stress and mitochondrial damage occur in sepsis. Manganese superoxide dismutase (MnSOD) provides the main defence against oxidative stress within mitochondria. Ala9Val is a single nucleotide polymorphism (SNP) in the MnSOD gene, predicted to affect intra-mitochondrial transport of the enzyme. We found a significant difference in the genotype frequency between healthy subjects (n = 100) and patients with sepsis (n = 40, p = 0.009). For assessment of functionality ten healthy subjects of each homozygous genotype (A/A or V/V) were studied. Peripheral blood mononuclear cells were separated and incubated for 18 h with lipopolysaccharide (LPS), followed by analysis of mitochondrial and cytosolic fractions. There was no difference between genotypes in MnSOD activity and cytochrome c concentration, and minor differences in total antioxidant capacity (TAC) and mitochondrial membrane potential, which did not affect response to LPS. Despite predictions from structural enzyme studies that mitochondrial trafficking would be affected by the Ala9Val polymorphism of the MnSOD gene had little functional effect.     

Effect of cold acclimation on the antioxidant defense system of two larval lepidoptera (noctuidae)

Activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione-S-transferase (GST), as well as total glutathione (tGSH) concentration were analyzed in the hemolymph and fat body of the European corn borer Ostrinia nubilalis Hubn. and the Mediterranean borer Sesamia cretica Led. (Lepidoptera, Noctuidae). Controls were maintained at 8°C while experimental groups of larvae were exposed to –3°C for ten days and then to –12°C for 23 days (only for Ostrinia). Cold exposure significantly increased fat body SOD, GR, and GST activities of Ostrinia larvae. Only GST activity and tGSH levels increased significantly in Ostrinia larval hemolymph on cold exposure. In Sesamia larvae after cold exposure, hemolymph CAT activity was significantly lower, while fat body tGSH increased. The antioxidant defense systems of these two species show differences, probably influenced by their respective cold-hardiness metabolism. According to its antioxidant profile, the response of Ostrinia suggests a significant physiological alteration in its metabolism during cold exposure, indicating a compensatory mechanism. By contrast this is not evident in Sesamia.Arch. Insect Biochem. Physiol. 36:1–10, 1997. © 1997 Wiley-Liss, Inc.     

Fluidity and oxidative stress in erythrocytes from very low birth weight infants during their first 7 days of life

Objective: To study the evolution of lipid peroxidation, enzymatic antioxidants response, lipid profile and membrane fluidity in erythrocytes from very low birth weight (VLBW) infants during their first 7 days of extra-uterine life.

Study design: One hundred and twenty infants were selected and divided in two groups according to their weight and gestational age. Hydroperoxides, fatty-acid profile, fluidity (DPH and TMA-DPH) and catalase, SOD and GPx activities were measured in erythrocytes.

Results: VLBW group showed higher concentration of hydroperoxides and lower membrane fluidity during the first 72 h, lower SOD activity during the first 3 h and higher GPx activity during the first 7 days of life. Also, this group showed lower n-3 polyunsaturated fatty-acids percentage with respect to the term group.

Conclusion: Erythrocytes from VLBW infants showed higher oxidative damage and lower fluidity in their membranes, at least during the first 3 days of extra-uterine life, which may cause alterations in their functions and flexibility.     

Pro-antioxidant ratio in healthy men exposed to muscle-damaging resistance exercise

The purpose of this study was to compare the pro-antioxidant status in healthy men exposed to muscle-damaging resistance exercise, and to investigate the practical application of Loverro's coefficient (P/A ratio) to evaluate the presence of oxidative stress. Twenty-eight healthy men were assigned to two groups performed multi-joint (M) or single-joint (S) resistance exercise. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) as well as the concentration of lipid peroxidation products (TBARS) in blood were evaluated. The P/A ratio was calculated from the mean values of erythrocyte TBARS, SOD, CAT and GPx. Creatine kinase (CK) activity was used as a marker of muscle damage. The applied resistance exercises triggered off the changes in pro-antioxidant ratio towards peroxidation which was proved by significant increase in erythrocyte TBARS concentration in M (+25%) and S (+27%) groups. Plasma TBARS increased only after multi-joint resistance exercise and correlated with erythrocyte P/A ratio (r = 0.536, P < 0.01). The multi-joint exercise caused decrease in SOD activity by 28% whereas the single-joint resistance exercise elevated enzyme activity by 20%. Activities of the other antioxidant enzymes changed simultaneously i.e. CAT activity increased by 14%-16% immediately after exercise, and GPx activity declined by 18%-34% during recovery in M and S groups. Even though, all erythrocyte parameters significantly changed following multi-joint and single-joint resistance exercises, the assessment of pro-antioxidant ratio showed the considerable increase in P/A only in M group. In summary, an analysis of pro- and antioxidant parameters showed significant changes in response to muscle-damaging exercise and demonstrated the practical application of P/A ratio to evaluate the risk of oxidative stress in athletes.     

<Emphasis Type="Italic">PARP-1 Val762Ala</Emphasis> polymorphism,CagA<Superscript>+</Superscript><Emphasis Type="Italic">H. pylori</Emphasis> infection and risk for gastric cancer in Han Chinese population

Introduction PARP-1 plays important role in the BER (base excision repair) and maintenance of genomic integrity. Previous study found the Val762Ala genetic variant in the PARP-1 gene contributed to susceptibility of some cancers and decreased PARP-1 enzyme activity in response to oxidative damage. Helicobacter pylori (H. pylori) infection was thought to be one of the major causes of gastric cancer. In this study, we investigated the association between the PARP-1 Val762Ala polymorphism, CagA⁺ H. pylori infection, and the risk for gastric cancer. Methods This hospital-based, case–control study was performed involving 556 individuals (236 cases with gastric cancer and 320 controls without evidence of neoplasm and gastrointestinal disease) using a PCR-RFLP method. Chi-square test and logistic regression analysis were used to count OR and 95% CI. Results 762Ala/Ala genotype was overrepresented in the cases (16.9%) compared with controls (10.3%), (OR, 1.942; 95% CI, 1.157–3.257, P = 0.011). Multivariate analysis showed that two factors were significantly associated with risk of gastric cancer, including CagA⁺ H. pylori infection (OR, 2.562; 95% CI, 1.174–5.240, P = 0.037), PARP-1 762AA genotype (OR, 1.772; 95% CI, 1.065–3.867; P = 0.042). Stratification analysis indicated that among Cag⁺ H. pylori positive subjects, 762Ala/Ala carriers had higher risk for developing gastric cancer compared with 762Val/Val carrier (OR, 2.337; 95% CI, 1.148–4.758; P = 0.017). Conclusion PARP-1 762Ala/Ala could be a risk factor for gastric cancer in Han Chinese population; PARP-1 762Val/Ala polymorphism and Cag⁺ H. pylori infection jointly contribute to higher risk for gastric cancer.     

Association between Gene Polymorphism of Manganese Superoxide Dismutase and Prostate Cancer Risk

Manganese superoxide dismutase (MnSOD) is the most effective antioxidant enzyme in mitochondria and protects cells from reactive oxygen species‐induced oxidative damage. The aim of this study was to investigate the association between MnSOD Ala‐9Val gene polymorphism and prostate cancer (PCa) risk in Turkish men with prostate cancer. 33 patients with PCa and 81 control individuals were included in the study. We observed an association between MnSOD Ala/Ala frequency and a higher PCa risk. In addition, we found that the increased risk of early‐onset PCa (under age of 65) in the men homozygous for Ala allele was higher than the men homozygous for Val allele. However, we determined that MnSOD Ala‐9Val genotype was not associated with the aggressiveness of the disease. The results of our study suggest that MnSOD Ala/Ala genotype may influence on early‐onset of PCa patients, but no effect on subsequent development of the disease in Turkish men. However, our study has a limitation that is small numbers of individuals for cases and controls. Therefore, the presented study limited our statistical power to fully investigate the gene polymorphism on cancer risk. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:213‐218, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21472     

The impact of OGG1, MTH1 and MnSOD gene polymorphisms on 8-hydroxy-2′-deoxyguanosine and cellular superoxide dismutase activity in myocardial ischemia–reperfusion

Ischemia–reperfusion (I/R) injury, by inducing oxidative DNA damage, is one of the leading causes of increased patient morbidity and mortality in coronary artery by-pass grafting (CABG) surgery. 8-Hydroxyguanine (8-OHG) is an important oxidative base lesion. The 8-oxoguanine glycosylase (hOGG1) and hMTH1, which have several polymorphisms, remove 8-OHdG from the nucleotide pool. We investigated whether there are any correlations the biomarkers of oxidative stress (superoxide dismutase; SOD and 8-OHdG in serum) with genotype for two DNA repair genes (OGG1 and MTH1) and an antioxidant enzyme gene (manganese superoxide dismutase; MnSOD). Therefore, we measured DNA damage (8-hydroxy-2-deoxyguanosine; 8-OHdG) and endogenous antioxidant activity (SOD) at five different time points (T1, before anesthesia; T2, after anesthesia; T3, after ischemia; T4, after reperfusion and T5, after surgery). and also, MnSOD and MutT homolog 1 (MTH1) genes polymorphisms were genotyped by polymerase chain reaction–restricted fragment length polymorphism (PCR–RFLP) in patients undergoing coronary artery by-pass grafting (CABG) surgery. No statistically significant differences were detected in the levels of 8-OHdG and SOD in serum in terms of OGG1 Ser326Cys, MTH1 Val83Met and MnSOD Ala16Val genetic polymorphisms. Our results suggest that OGG1, MTH1 and MnSOD gene polymorphisms are not genetic risk factors for I/R injury.     

Impact of umbelliferone on erythrocyte redox status in STZ-diabetic rats

Oxidative stress is currently hypothesized to be a mechanism underlying diabetes. The present study was designed to evaluate the effect of umbelliferone (UMB), a derivative of coumarin, on erythrocyte lipid peroxidation, antioxidants, and lipid profile in normal and streptozotocin (STZ) diabetic rats. Diabetes was induced in adult male albino rats of Wistar strain, weighing 180 to 200 g, by the administration of STZ (40 mg/kg/b-wt) intraperitonially. The normal and diabetic rats were treated with UMB in 10 percent dimethyl sulfoxide (DMSO) dissolved in water for 45 days. The diabetic rats had elevated levels of blood glucose and lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD), and lipid hydroperoxide (HP) and decreased levels of nonenzymatic antioxidants (Vitamin C and reduced glutathione [GSH]), elevated levels of vitamin E, and elevated levels of enzymatic antioxidants (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]), elevated glucose-6-phosphate dehydrogenase activity, and altered lipid profile (cholesterol and phospholipids) in erythrocytes. These changes were reversed by treatment with UMB. Thus, our results indicate that the administration of UMB shows promising potential for the restoration of normal blood glucose levels, erythrocyte lipid peroxidation, antioxidants, and lipid profile in STZ-diabetic.