S. Büyükkocak

Impaired antioxidant defense system in the kidney tissues from rabbits treated with cyclosporine. Protective effects of vitamins E and C.

Enzymatic antioxidant defense system and antioxidant defense potential (AOP) were studied in kidney tissue from rabbits treated with cyclosporine (CsA, 25 mg/kg/day), antioxidant vitamins (E, 100 mg/kg/day plus C, 200 mg/kg/day), and CsA plus antioxidant vitamins, and in kidney tissue from control animals. Although no change was observed in superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) and catalase (CAT) activities were found decreased in kidney tissue exposed to CsA for 10 days compared with control tissue. The level of thiobarbituric acid-reagent substances (TBARS) was higher and antioxidant defense potential (AOP) lower in the CsA-treated group compared with the other groups. Histopathological examination reveals important subcellular damage in the renal tissue from the animals treated with CsA. Antioxidant vitamin therapy caused full improvement in the enzyme activities, TBARS levels and AOP, but the subcellular damage was partly ameliorated in the CsA plus vitamin group. Results suggest that CsA impairs the antioxidant defense system and reduces the antioxidant defense potential in the renal tissue. Antioxidant vitamin treatment protects the tissue in part against toxic effects of the drug.

Effects of cigarette smoking with different tar content on erythrocyte oxidant/antioxidant status.

Abstract In this study, the effects of cigarettes with differing tar content on erythrocyte oxidant/antioxidant status was investigated. Malondialdehyde (MDA) as an indicator of oxidant status and superoxide radical scavenger activity (SSA) as an indicator of antioxidant status were measured in erythrocytes from 20 smokers and 10 non‐smoker controls. Ten of the 20 smoking subjects smoked five cigarettes with full flavour low tar (FFLT with 12 mg tar) and the others smoked five cigarettes with full flavour high tar (FF with 23 mg tar) over 1 hour. Initial blood samples from both groups at fasting, followed by further samples from smokers at 1.5 hours and 3 hours after smoking. Initial erythrocyte MDA level and SSA activity were found to be higher in the smoking groups compared to non‐smokers. Furthermore, both parameters were significantly higher at the 1.5‐hour and 3‐hour erythrocyte samples when compared to initial values in the FFLT group. However, there were no statistically significant differences between SSA values established at different times in FF group. Results suggest that smoking causes oxidant load in the erythrocytes. Although a compensatory mechanism (i.e. increased SSA activities) develops in the FFLT group after smoking, this cannot prevent peroxidation reactions (i.e. increased MDA levels) in the erythrocytes. As to the types of cigarettes, both seem to have oxidant potential, but oxidation degree in the FFLT group is higher than that of FF group. These results suggest that antioxidant supplementation to smokers might be beneficial to decrease cellular oxidation damages.

Antioxidant Defense Potential of Rabbit Renal Tissues after ESWL: Protective Effects of Antioxidant Vitamins

Antioxidant defense potential, malondialdehyde (MDA) levels, and relative hydroxyl radical (OH·) concentrations were measured in order to establish the effects of extracorporeal shock wave lithotripsy (ESWL) on free radical production and antioxidant defense potential of the rabbit kidney tissues. Electron microscopic examination was also performed to observe ultrastructural changes. The antioxidant defense potential of the ESWL-treated tissues was found to be reduced, and the MDA levels increased as compared with controls. Vitamin (vitamin E plus C combination) pretreatment ameliorated antioxidant defense potential in part, prevented increases in MDA levels in the ESWL-treated tissues, and increased the antioxidant defense potential in the control kidney tissues. After ESWL, a significant amount of OH· radical was measured in the affected tissue. This revealed the source of oxidant stress and peroxidation reactions in the ESWL-treated kidney tissue. Vitamin pretreatment caused significant reduction in the OH· radical concentration. In the electron microscopic investigation, some significant subcellular changes, such as endothelial injury, loss of foot processes, damage of glomerular basal membrane, etc., were observed in the ESWL-treated renal tissue slices. Vitamin pretreatment to a great extent prevented formation of these subcellular changes. Our results suggest that the antioxidant capacity of the kidney tissue was reduced after ESWL treatment and that the tissue was exposed to oxidant stress. Vitamin pretreatment exerted significant protection against the radical damage.

Effects of smoking on plasma and erythrocyte antioxidant defense systems.

In this study, activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) enzymes were measured in the erythrocytes, and levels of thiobarbituric acid-reactive substances (TBARS) and antioxidant potential (AOP) values were measured in both erythrocyte and plasma samples from smokerS and nonsmokers. No significant differences were observed in erythrocyte parameters, serum triglycerides, and total cholesterol. AOP was significantly lower and TBARS level higher in the plasma samples from smokers compared with those of nonsmokers. Results suggest that smoking causes no impairment in the enzymatic antioxidant defense system and does not lead to oxidant stress in the erythrocytes, possibly because these cells have potent antioxidant defense capacity.

Comparison of Antioxidant Potentials of Red Wine, White Wine, Grape Juice and Alcohol

Antioxidant potential (AOP) and non-enzymatic superoxide radical scavenger activity (NSSA) values of red wine, white wine, grape juice and ethyl alcohol were assessed and values were compared. The effects of these beverages on serum AOP and NSSA values were also measured in vitro. Red wine, white wine and grape juice exert strong antioxidant activity in similar degrees and all produce significant effects on serum AOP and NSSA values. However, ethyl alcohol does not have either AOP or NSSA, nor does it have an effect on serum AOP or NSSA values. AOP values (nmol/ml h) of red wine, white wine and grape juice were 20.8 +/- 4.2, 23.2 +/- 4.0 and 24.6 +/- 4.8, respectively. NSSA values (U/ml) of red wine, white wine and grape juice were 30.4 +/- 6.8, 26.8 +/- 5.6 and 32.6 +/- 5.8, respectively. There were no statistically meaningful differences between AOP and NSSA values of the groups (p > 0.05 for all). Results suggest that red wine, white wine and grape juice all have high antioxidant potential to protect cellular structures against peroxidation reaction owing to their rich phenolic contents.

Aspirin impairs antioxidant system and causes peroxidation in human erythrocytes and guinea pig myocardial tissue

This study aims to investigate possible effects of aspirin treatment on cellular oxidant/antioxidant system. In the first part of the study, 15 guinea pigs were given aspirin at three different doses (2200, 440 and 10 mg/kg/day) for 30 days and five were fed on the same diet without aspirin. After a month, animals were killed and their hearts were removed for use in analyses. In the other part, after fasting blood samples were obtained from 11 volunteer subjects, they were given aspirin (approximately 10 mg/kg/day) for 30 days and second blood samples were obtained after 1 month. Five volunteer subjects also participated as placebo control. Oxidant/antioxidant parameters, namely superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA), nonenzymatic superoxide scavenger activity (NSSA), susceptibility to oxidation (SO) and antioxidant potential (AOP) values, were assayed in the samples. Antioxidant system was found to be impaired in the heart tissue from guinea pigs and in the erythrocytes from volunteer subjects. AOP and NSSA values were lower and MDA higher after aspirin treatment in both heart tissues and erythrocytes. In guinea pig heart tissue, SO was lower, but GSH-Px and CAT were unchanged after aspirin treatment. In human erythrocytes, SO was unchanged, but GSH-Px and CAT activities were increased after aspirin treatment. Changes in guinea pig heart tissues from animals treated with higher aspirin doses were more drastic relative to those of human erythrocytes, but no meaningful differences were observed between analysis parameters of control and lower-dose (10 mg/kg/day) aspirin-treated animals. Our results suggest that high-dose aspirin exerts significant toxicity to guinea pig myocardium and normal dose aspirin may cause peroxidation in the human erythrocytes due to its oxidant potential. We suppose that antioxidant supplementation may be beneficial for the people using aspirin for longer periods in order to prevent peroxidation damages.

Reduced antioxidant defense capacity in myocardial tissue from guinea pigs treated with 5-fluorouracil

Antioxidant defense capacity was investigated in myocardial tissue from guinea pigs treated with 5-fluorouracil (5-FU) at a dose of 400 mg/kg/d daily for 5 d administered intraperitonally. Treatment with 5-FU lowered the activities of cardiac superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) accompanied by higher catalase (CAT) activity. Further, antioxidant potential (AOP) values were lower but oxidation resistance (OR) and malondialdehyde (MDA) levels were higher in the 5-FU-treated tissue. With regard to myocardial iron (Fe) and copper (Cu) levels, no significant differences were found between the groups. Results suggest that 5-FU treatment causes impairment in the myocardial antioxidant defense system and leads to cardiac peroxidation. It has been postulated that these changes might be responsible for the 5-FU cardiotoxicity seen in some patients, and antioxidant therapy might provide a therapeutic advantage.Antioxidant defense capacity was investigated in myocardial tissue from guinea pigs treated with 5-fluorouracil (5-FU) at a dose of 400 mg/kg/d daily for 5 d administered intraperitonally. Treatment with 5-FU lowered the activities of cardiac superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) accompanied by higher catalase (CAT) activity. Further, antioxidant potential (AOP) values were lower but oxidation resistance (OR) and malondialdehyde (MDA) levels were higher in the 5-FU-treated tissue. With regard to myocardial iron (Fe) and copper (Cu) levels, no significant differences were found between the groups. Results suggest that 5-FU treatment causes impairment in the myocardial antioxidant defense system and leads to cardiac peroxidation. It has been postulated that these changes might be responsible for the 5-FU cardiotoxicity seen in some patients, and antioxidant therapy might provide a therapeutic advantage.

Isoflurane impairs antioxidant defence system in guinea pig kidney.

PurposeTo investigate whether free radical metabolism is changed due to isoflurane treatment and, if so, to elucidate the role of changed free radical metabolism in the nephrotoxicity.Materials and methodsFifteen guinea pigs were used in the study. Five were treated with isoflurane in oxygen, five with oxygen and five were controls. Animals were exposed to isoflurane and oxygen three times. Each treatment was performed for 30 min once a day for three consecutive days. Activities of free radical enzymes, Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px); values of antioxidant parameters, antioxidant potential (AOP), non-enzymatic Superoxide radical scavenger activity (NSSA) and oxidation resistance (OR) and, level of an oxidant parameter namely, malondialdehyde (MDA) were determined in the renal tissues of the groups. Blood was also obtained for serum creatinine and urea analyses.ResultsAOP, NSSA, SOD and CAT activities were decreased; (0.0188 ± 0.0026 vs 0.0156 ± 0.0015,P < 0.025; 8.72 ± 1.80vs 6.40 ± 1.22,P < 0.05; 76.71 ± 18.54vs 52.79 ± 1 1.68,P < 0.025; 71.26 ± 15.58vs 55.39 ± 8.83;P < 0.05, respectively) but, MDA level, OR value and GSH-Px activities increased (10.89 ± 1.57 vs 1 5.87 ± 2.97,P < 0.0 1; 0.84 ± 0.34vs 2.28 ± 1.39,P < 0.05; 1.45 ± 0.83 vs 3.45 ± 1.20,P < 0.01, respectively) in kidney tissues from isoflurane-treated group compared with controls. No differences were observed between control and oxygen groups with regard to all analysis parameters except GSH-Px.ConclusionIsoflurane impairs the antioxidant defence system and this oxidant stress may play a part in the isoflurane-induced renal toxicity.RésuméObjectifVérifier si le métabolisme des radicaux libres est changé par l’usage d’isoflurane et, si c’est le cas, préciser le rôle de ce métabolisme transformé sur la néphrotoxicité.MéthodeL’étude a porté sur quinze cobayes dont cinq ont reçu de l’isoflurane dans de l’oxygène, cinq, de l’oxygène et cinq ont servi de témoins. Les animaux ont été exposés trois fois à l’isoflurane et à l’oxygène. Chaque traitement a été réalisé pendant 30 min, une fois par jour, trois jours consécutifs. On a déterminé dans les tissus rénaux des cobayes: les activités des enzymes des radicaux libres, la superoxyde-dismutase (SOD), la catalase (CAT) et la glutathion-peroxydase (GSH-Px); les valeurs des paramètres antioxydants, le potentiel antioxydant (PAO), l’activité non enzymatique des piégeurs de radicaux superoxydes (ANPS) et la résistance à l’oxydation (RO) ainsi que le niveau d’un paramètre oxydant, à savoir, le malondialdéhyde (MDA). On a aussi prélevé du sang aux fins d’analyses de la créatinine et de l’urée sériques.RésultatsLes activités des PAO, ANPS, SOD et CAT étaient diminuées (0,0188 ± 0,0026vs 0,0156 ± 0,0015,P < 0,025; 8,72 ± 1,80vs 6,40 ± 1,22,P < 0,05; 76,71 ± 18,54vs 52,79 ± I 1,68,P < 0,025; 71,26 ± 15,58 vs 55,39 ± 8,83;P < 0,05, respectivement) mais le niveau de MDA, la valeur de la RO et les activités de la GSH- Px augmentés (10,89 ± 1,57vs 15,87 ± 2,97,P < 0,01; 0,84 ± 0,34vs 2,28 ± 1,39,P < 0,05; 1,45 ± 0,83vs 3,45 ± 1,20,P < 0,01 respectivement) dans les tissus rénaux du groupe traité à l’isoflurane comparé au groupe témoin. Aucune différence n’a été relevée entre le groupe témoin et celui qui a reçu de l’oxygène quant aux analyses de tous les paramètres, sauf la GSH-Px.ConclusionL’isoflurane nuit au système de défense antioxydant et ce stress oxydant peut faire partie de la toxicité rénale induite par l’isoflurane.

The effects of cyclosporine on antioxidant enzyme activities and malondialdehyde levels in rabbit hepatic tissues

Possible molecular mechanisms leading to cyclosporine-induced hepatotoxicity has not been cleared yet. Therefore, investigation of antioxidant status of hepatic tissues exposed to cyclosporine A (CsA) and of free radical involvement in the CsA-induced hepatotoxicity seems of importance. For this aim, 20 rabbits were used in the study. In each group (control, CsA, CsA plus vitamin and, vitamin only) there were 5 animals. CsA was given orally (25 mg/kg/day) for 10 days. Vitamins E (100 mg/kg/ day) and C (200 mg/kg/day) combination was injected intramuscularly. After 10th day, animals were killed, and livers were prepared for the enzymatic assays. Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) and, malondialdehyde (MDA) levels were determined in the supernatant fractions. Lowered SOD, unchanged GSH-Px and, increased CAT activities and MDA levels were detected in hepatic tissues of rabbits treated with CsA as compared with controls. In the CsA plus vitamin group, SOD activity was found to be higher, GSH-Px and CAT activities unchanged and MDA levels lower than the CsA group. In the vitamin-treated group, all of the enzyme activities were higher than the controls but MDA levels were unchanged. Correlation analysis revealed some significant differences between the groups. Results suggest that cyclosporine impairs the antioxidant defense system and thus, leads to oxidant stress and peroxidation in rabbit hepatic tissues. It has been established that this process can be prevented by antioxidant vitamin supplementation.

Erythrocyte oxidant/antioxidant status of diabetic patients

Present study aims to establish erythrocyte oxidant/antioxidant status in diabetic patients with and without atherosclerotic complications. Fasting blood samples were obtained from 23 diabetic and 12 control subjects. Thirteen patients had no disease other than diabetes mellitus and 10 patients had also atherosclerosis in addition to diabetes mellitus. Erythrocyte antioxidant potential (AOP) and thiobarbituric acid reagent substances (TBARS) levels were measured in these patients and results were compared with those of controls, who were chosen among healthy subjects. Results suggest that although there is an oxidant stress in the erythrocytes of diabetics, this is not due to reduced erythrocyte antioxidant defence potential but, rather, increased free radical production possibly due to hyperglycemia.