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Methotrexate Causes Oxidative Stress in Rat Kidney Tissues

Aim. Methotrexate (MTX), a folic acid antagonist, is one of the chemotherapeutic agents widely used in the treatment of some types of cancers. Nephrotoxicity is one of the complications of MTX treatment. The aim of this study was to investigate possible effects of MTX treatment on the oxidant/antioxidant status in rat kidney tissues and enzymatic mechanisms leading to nephrotoxicity. Methods. For this aim, 10 Sprague-Dawley type female rats of 4 weeks old were used in the study. The animals were divided into two groups randomly. Five of them were used as control, and the others were treated with MTX intravenously (60 mg/m2 of body surface area per week) for 7 weeks. At the end of this period, they were sacrificed, and kidney tissues were removed to be used in the analyses of malondialdehyde (MDA) levels, antioxidant potential (AOP) values, and superoxide dismutase, catalase, glutathione peroxidase, xanthine oxidase, adenosine deaminase, and 5′ nucleotidase enzyme activities. Results. There was significant increase in the MDA level in the MTX group compared with the control group (1.74 ± 0.23 nmol/mg vs. 1.04 ± 0.30 nmol/mg; p < 0.05, respectively). There were however no meaningful differences between enzyme activities and AOP values of the groups. Conclusion. It has been suggested that MTX leads to oxidative stress in rat kidney tissues, which might be one of the reasons for MTX-induced nephrotoxicity.

Aqueous extract of Urtica dioica makes significant inhibition on adenosine deaminase activity in prostate tissue from patients with prostate cancer.

Aim: Investigation of possible effects of aqueous extract of urtica dioica leaves on adenosine deaminase activity in prostate tissue from patients with prostate cancer. Methods: Ten prostate tissues from patients with pathologically proven localized prostate cancer (Gleason scores 4 to 7) were used in the study. In the tissues, ADA activities with and without preincubation with different amounts of urtica dioica extracts were performed. Results: Aqueous extract of urtica dioica results in significant inhibition on adenosine deaminase (ADA) activity of prostate tissue. Conclusion: ADA inhibition by urtica dioica extract might be one of the mechanisms in the observed beneficial effect of urtica dioica in prostate cancer.

Effects of garlic consumption on plasma and erythrocyte antioxidant parameters in elderly subjects.

Background: The oxidative stress theory of aging is one of the most widely acknowledged theories of aging. The intake of fruits and vegetables with antioxidant power is associated with a reduced incidence of many chronic diseases of aging. Objective: The effects of ingesting garlic on plasma and erythrocyte antioxidant parameters of elderly subjects were investigated in this study. Methods: 13 subjects (mean age 70.69 ± 4.23) participated in the study. They ingested garlic at the daily dose of 0.1 g/kg b.w. for 1 month. Before and after this period, fasting blood samples were obtained, and oxidant [malondialdehyde (MDA) and xanthine oxidase (XO)] and antioxidant [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] parameters were studied in erythrocytes, and MDA levels were studied in plasma samples obtained from the subjects. Routine blood biochemical parameters were also measured in blood samples. Results: In the plasma fraction and erythrocyte hemolysate, MDA levels were found to be significantly lower, but erythrocyte GSH-Px and SOD activities were significantly higher in the second samples relative to the first ones. XO activity was found to be lower in the second samples, but this decrease was not statistically meaningful. LDL cholesterol was found to be significantly lower in the second samples relative to the first ones. Conclusion: Our results show that ingestion of garlic leads to significantly lowered plasma and erythrocyte MDA levels and to increased activities of some antioxidant enzymes, which indicates that consumption of garlic decreases oxidation reactions. It is quite possible that reduced peroxidation processes due to garlic consumption may play a part in some of the beneficial effects of garlic in elderly subjects.

Effects of isoflurane on nitric oxide metabolism and oxidant status of guinea pig myocardium

Background: Volatile anesthetics (VAs) have been shown to enhance myocardial recovery during reperfusion, the mechanism of which has not been clarified yet. It has been supposed that this effect of VAs may appear through antioxidative mechanisms.

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.

Effects of apple consumption on plasma and erythrocyte antioxidant parameters in elderly subjects

The effects of apple consumption on plasma and erythrocyte antioxidant parameters of elderly subjects were investigated in this study. Fifteen elderly subjects (mean age 71.86 ± 4.17) participated in the study. They consumed an apple a day for 1 month. Before and after this period, fasting blood samples were obtained, and oxidant (malondialdehyde [MDA]) and antioxidant (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT], and antioxidant potential [AOP]) parameters were studied. MDA and AOP levels were studied in plasma, and SOD, GSH-Px, and CAT activities and MDA levels were measured in the erythrocytes. In the erythrocytes, GSH-Px and SOD activities were found to be higher (p < .001 and p < .01), but MDA levels were lower in the second samples relative to the first ones. In the plasma, AOP value was found to be higher in the second samples relative to first ones (p < .001). No differences were found, however, between the routine blood parameters such as total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, high-density-lipoprotein cholesterol, and triglyceride levels. The results show that consumption of apple leads to significant increases in the activities of some antioxidant enzymes and in the antioxidant potential values of the blood, and that decreases oxidation reactions in the body in significant amount. It is quite possible that reduced peroxidation processes owing to consumption of this fruit may play a part in some of their beneficial effects in the elderly subjects.

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.

Black grape and garlic extracts protect against cyclosporine a nephrotoxicity

The aim of this study was to determine if the natural antioxidant foods, dried black grape and garlic, protect against cyclosporine nephrotoxicity. Forty-two Sprague–Dawley rats were given Cyclosporine A (CsA) orally for 10 days, with the antioxidant food supplementation begun 3 days before CsA treatment and continued during the study period (totaling 13 days). In each group (control, CsA alone, CsA plus black grape, CsA plus aqueous garlic extract, aqueous garlic extract alone and black grape alone), there were 7 animals. At the end of the study period, the animals were sacrificed; their kidneys were removed and prepared for biochemical and histopathological investigations. Oxidant (xanthine oxidase enzyme and malondialdehyde) and antioxidant (superoxide dismutase, glutathione peroxidase and catalase enzymes) parameters were measured in the kidney tissues of the groups. Histopathological examinations of the tissues were also performed. It has been found that CsA creates oxidant load to the kidneys through both xanthine oxidase activation and impaired antioxidant defense system, which accelerates oxidation reactions in the kidney tissue. Supplementation with either dried black grape or aqueous garlic extract led to reduced malondialdehyde level in the kidney tissue possibly, by preventing oxidant reactions. In conclusion, the results suggest that impaired oxidant/antioxidant balance may play part in the CsA-induced nephrotoxicity, and some foods with high antioxidant power may ameliorate this toxicity, in agreement with studies with antioxidant vitamins.

Oxidant/Antioxidant Status of Erythrocytes from Patients with Chronic Renal Failure: Effects of Hemodialysis

Objective: It has been suggested that oxidative processes may be increased in patients with chronic renal failure (CRF), and that this is a possible factor contributing to the development of anemia and atherosclerosis, characteristic complications of CRF. The aim of this study was to investigate erythrocyte oxidant/antioxidant status in patients with CRF and to elucidate possible effects of hemodialysis on erythrocyte antioxidant system. Methods: Fasting blood samples were obtained from 33 patients with CRF and from 12 healthy controls. Of the patients, 17 subjects were under regular hemodialysis. Values of the activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and antioxidant potential, nonenzymatic superoxide radical scavenger activity (NSSA) and levels of thiobarbituric acid reagent substances (TBARS) were measured in the erythrocytes from both patients and controls. Results: Antioxidant potential and NSSA values were found to be significantly decreased, while TBARS levels were increased in the erythrocytes of patients. SOD activity was found to be unchanged, but GSH-Px and CAT activities were significantly lower in the patient group. Moreover, the erythrocyte TBARS level in the hemodialysis group was higher than in the controls and nonhemodialysis patients. Conclusion: The results suggest that antioxidant potential is reduced due to impaired antioxidant system in erythrocytes from patients with CRF and that oxidant stress causes significant peroxidation. Hemodialysis is determined to further increase oxidative reactions. These changes seem to contribute to the occurrence of some complications of CRF. Therefore, it has been suggested that antioxidant supplementation may give beneficial results for these patients.