H. Serdar Öztürk

ACTIVITIES OF TOTAL, CYTOPLASMIC, AND MITOCHONDRIAL SUPEROXIDE DISMUTASE ENZYMES IN SERA AND PLEURAL FLUIDS FROM PATIENTS WITH LUNG CANCER

In this study, total cytoplasmic (Cu, Zn‐SOD) and mitochondrial (Mn‐SOD) superoxide dismutase activities were measured in sera and pleural fluids from patients with squamous cell carcinoma of the lung. The results were compared with those of control subjects and those of patients with tuberculosis and chronic heart failure. Serum activities were found higher in all patient groups compared to control group. Highest values were however in tuberculosis group. In the correlation analysis, meaningful intra‐ and inter‐correlations were established between enzyme activities in the samples.

CISPLATIN INDUCES ACUTE RENAL FAILURE BY IMPAIRING ANTIOXIDANT SYSTEM IN GUINEA PIGS: EFFECTS OF ANTIOXIDANT SUPPLEMENTATION ON THE CISPLATIN NEPHROTOXICITY

This study aims to investigate the role of oxidants in cisplatin-induced nephrotoxicity. Cisplatin was administered intraperitoneally (i.p.) in a single dose (5 mg/kg) and guinea pigs were killed either after 24 h or 7 days. The same experiment was performed using animals treated with vitamins C and E combination and a natural antioxidant extract (SARMEX®). The kidneys were then removed to be used in the analyses. Blood samples were also obtained from the animals to be used in routine biochemical assays. Twenty-four hours after treatment there was a significant decrease in the renal activities of total superoxide scavenger activity (TSSA), superoxide dismutase (SOD) and catalase (CAT) accompanied by a rise in malondialdehyde (MDA) levels. After 7 days, the fall in kidney enzymatic activities was far greater, while the increase in blood urea (BUN) and creatinine (CRE) was marked. Treatment with antioxidants causes significant increases in renal TSSA (7 day), non-enzymatic superoxide scavenger activity (NSSA) (24 h and 7 day) and SOD (7 day) activities, does not change glutathione peroxidase (GSH-Px) activity and decreases renal MDA (24 h and 7 day), blood BUN (7 day) and CRE (7 day) levels. Our results suggest that cisplatin treatment impairs both enzymatic and non-enzymatic antioxidant systems and causes peroxidation in the renal tissue, which leads to kidney failure. Antioxidant supplementation strengthens the renal antioxidant system, eliminates oxidation reactions, and prevents cisplatin-induced kidney failure.

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 Garlic Extract Supplementation on Blood Lipid and Antioxidant Parameters and Atherosclerotic Plaque Formation Process in Cholesterol-Fed Rabbits

Objective: Possible effects of garlic extract supplementation on blood oxidant/antioxidant status, blood lipid profile and coronary plaque formation process were investigated in cholesterol-fed rabbits. Methods: Thirty-one male rabbits of New Zealand strain were used. Twenty-two animals were given cholesterol for 4 months. Seven of them were sacrificed to investigate plaque formation and to measure blood parameters. Seven of the remaining 15 animals were fed on normal laboratory diet and others normal diet plus garlic extract for additional 3 months. Blood antioxidant and lipid parameters were measured and histological examination was made. Results: Total, HDL and LDL cholesterol levels were found to be significantly higher in the Cholesterol Group relative to controls. In the histological investigation, a dense atherosclerotic plaque formation was observed in the aortas of this group. In the Normal Diet Group, total, HDL and LDL cholesterol levels were higher relative to the control group. No significant differences were observed between plaque surface areas of the Cholesterol and Normal Diet Groups. In the Extract Group however, there were differences with regard to all the analysis parameters. Total, HDL and LDL cholesterol levels were found to be decreased in this group. There was significant reduction in the plaque surface area in the aortas of this group. Blood antioxidant potential (AOP) was higher than the other groups but, malondialdehyde (MDA) level and, value of susceptibility to oxidation (SO) were lower in the Extract Group relative to the other groups. There were however no significant differences between MDA and SO values of the Control and Extract Groups. Conclusions: Our results demonstrate that cholesterol supplementation leads to dense plaque formation in the aortas of the rabbits. Garlic extract supplementation ameliorates blood lipid profile and, Increases antioxidant potential. Extract treatment can significantly reduce plaque surface area in the aorta. Our results suggest that increased blood antioxidant potential due to extract supplementation might be one of the factors leading to this end.

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.

Blood oxidant/antioxidant status of atherosclerotic patients

In the present study, it is aimed to investigate oxidant/antioxidant status of plasma and erythrocytes from atherosclerotic patients and to establish the possible role of oxidant stress in the formation and progression of atherosclerosis. Antioxidant potential (AOP) values and malondialdehyde (MDA) levels were studied in erythrocyte and plasma samples from 40 atherosclerotic patients and 38 healthy controls. A total of 13 subjects in each group were smokers. AOP was found unchanged in erythrocytes but lower in plasma samples (P<0.0005) from atherosclerotic patients as compared with those of the controls. MDA levels were however higher in erythrocyte hemolysate (P<0.025), erythrocyte membrane (P<0.0005) and blood plasma samples (P<0.0005) from atherosclerotic patients than those of the controls. Moreover, AOP was found to be lower in plasma samples of smoker patients than that of non-smoker patients (P<0.05). In the control group, erythrocyte MDA level was higher in smoker group than that of non-smoker group (P<0.05). Results reveal the presence of oxidant stress in the blood samples from patients with atherosclerosis. It seems antioxidant therapy might give beneficial results for atherosclerotic patients.

The Effect of Red Wine on Blood Antioxidant Potential

We investigated the effects of red wine on blood antioxidant potential in an attempt to elucidate molecular mechanisms concerning the possible protective role of red wine in atherosclerosis. Volunteer subjects in the study group consumed a standard meal and drank red wine (5 mg/kg) while controls consumed the same meal and drank water. Over 4 1/2 hours, blood samples were taken, and malondialdehyde (MDA) and antioxidant potential (AOP, obtained from MDA levels before and after superoxide radical attack) values were measured in the plasma and erythrocytes. We found that AOP values of plasma and erythrocyte samples from the study group were at their highest after 1 1/2 hours and then declined to basal values at 4 1/2 hours. There were no statistically significant differences between the basal AOP values of the study group and the control group. With regard to MDA levels, gradual increases were seen in the plasma of the control group during the 3 hours after food, but no changes were seen in the plasma of the study group in this period. Although there were increases in erythrocyte MDA levels of both groups over 3 hours, the MDA production rate was significantly higher in the control group. Our results suggest that red wine causes significant increases in AOP values of plasma and erythrocytes, which may prevent cellular peroxidation reactions and lessen atherosclerotic complications through inhibition of LDL.