Effect of N‐acetylarginine,a metabolite accumulated in hyperargininemia,on parameters of oxidative stress in rats: protective role of vitamins and L‐NAME

In the present investigation, we initially evaluated the in vitro effect of N‐acetylarginine on thiobarbituric acid‐reactive substances (TBA‐RS), total sulfhydryl content and on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) in the blood, kidney and liver of rats. Results showed that N‐acetylarginine, at a concentration of 5.0 μM, decreased the activity of CAT in erythrocytes, enhanced TBA‐RS in the renal cortex, decreased CAT and SOD activities in the renal medulla and decreased CAT and increased SOD and GSH‐Px activities in the liver of 60‐day‐old rats. Furthermore, we tested the influence of the antioxidants, trolox and ascorbic acid, as well as of the N^ω‐nitro‐L ‐arginine methyl ester (L‐NAME) on the effects elicited by N‐acetylarginine on the parameters tested. Antioxidants and L‐NAME prevented most of the alterations caused by N‐acetylarginine on the oxidative stress parameters evaluated. Data indicate that oxidative stress induction is probably mediated by the generation of NO and/or ONOO^? and other free radicals because L‐NAME and antioxidants prevented the effects caused by N‐acetylarginine in the blood, renal tissues and liver of rats. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by N‐acetylarginine. Copyright © 2014 John Wiley & Sons, Ltd.     

Cardiac and renal antioxidant enzymes and effects of tempol in hyperthyroid rats

This study evaluated the activity of cardiac and renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR)] and whether chronic treatment with tempol, a cell membrane-permeable SOD mimetic, ameliorates the hypertension of hyperthyroidism. Two experiments were performed. In experiment I, the following four groups of male Wistar rats were used: control group and three groups that received thyroxine (T4) at 10, 50, or 75 microg x rat(-1) x day(-1). In experiment II, tempol was orally administered (18 mg x kg(-1) x day(-1)) to control and T4-treated (75 microg x rat(-1) x day(-1)) rats. All treatments were maintained for 6 wk. Body weight, tail systolic blood pressure (BP), and heart rate were measured one time a week, and direct BP and morphological, metabolic, plasma, and renal variables were measured at the end of the experiment. Enzymatic activities were measured in renal cortex and medulla and right and left ventricles. In renal cortex, SOD activity was decreased in the T4-75 group, and there was a dose-related increase in CAT activity and decrease in GPX and GR activities in T4-treated groups. Activity of all antioxidant enzymes was reduced in left ventricle in T4-50 and T4-75 groups and in right ventricle in the T4-75 group. Tempol reduced BP, plasma malondialdehyde, and total urinary excretion of F2 isoprostanes in hypertensive hyperthyroid rats but not in controls. Tempol did not improve cardiac hypertrophy, proteinuria, or creatinine clearance in hyperthyroid rats. In conclusion, the results obtained indicate that the activity of SOD, GPX, and GR in renal and cardiac tissues is decreased in hyperthyroidism and that antioxidant treatment with tempol ameliorates T4-induced hypertension.     

Proline Alters Antioxidant Enzyme Defenses and Lipoperoxidation in the Erythrocytes and Plasma of Rats: In Vitro and In Vivo Studies

In the present study, we investigated, in vivo (acute and chronic) and in vitro, the effects of proline on the activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase and superoxide dismutase (SOD) in erythrocytes and also investigated the effect on thiobarbituric acid-reactive substances (TBARS) in the plasma of rats. For the experiments, the number of animals per group ranged from eight to ten. For acute administration, 29-day-old rats received one subcutaneous injection of proline (18.2 μmol/g body weight) or an equivalent volume of 0.9% saline solution (control) and were killed 1 h later. For chronic treatment, buffered proline was injected subcutaneously into rats twice a day at 10 h intervals from the 6th to the 28th day of age. Rats were killed 12 h after the last injection. For in vitro studies, proline (30.0 μM to 1.0 mM) was added to the incubation medium. Results showed that acute administration of proline reduced CAT and increased SOD activities, while chronic treatment increased the activities of CAT and SOD in erythrocytes and TBARS in the plasma of rats. Furthermore, in vitro studies showed that proline increased TBARS in the plasma (0.5 and 1.0 mM) and CAT activity (1.0 mM) in the erythrocytes of rats. The influence of the antioxidants (α-tocopherol plus ascorbic acid) on the effects elicited by proline was also studied. Treatment with antioxidants for 1 week or from the 6th to the 28th day of age prevented the alterations caused by acute and chronic, respectively, proline administration on the oxidative parameters evaluated. Data indicate that proline alters antioxidant defenses and induces lipid peroxidation in the blood of rats.     

The effect of quercetin on renal ischemia and reperfusion injury in the rat

Renal ischemia-reperfusion injury occurs in many clinical conditions such as hypovolemic shock, thromboembolism, injury and after renal transplantation. Under these conditions, ROS are considered to be the reason for cellular damage. Bioflavonoids have antioxidant and renoprotective properties. We studied the effect of quercetin, a bioflavonoid, on ischemia and reperfusion in rats. The rats (n = 28) were separated into three groups. Group I was the control group. Animals in groups II (IR) and III (IR + Q) underwent 30 min ischemia and 45 min reperfusion, respectively. Rats, in group III, also received 50 mg kg(-1) quercetin before 45 min of reperfusion. The activities of SOD, CAT, GPx, and concentrations of GSH and GSSGR were determined in renal cortex and erythrocytes. Also, the levels of MDA in renal cortex and plasma, and XO in renal cortex were measured in these groups. The renal cortex XO levels in the IR group were higher than that of the control and IR+Q groups (p<0.001). The renal cortex and plasma MDA levels in the IR group were also found to be higher than the control and IR+Q groups (p<0.01, and p<0.001, respectively). However, a decrease in MAD level of the IR+Q group was found in renal cortex and erythrocytes. In addition, SOD, CAT, and GPx activities in renal cortex and erythrocytes of quercetin-treated animals were enhanced compared to animals of the IR group. Furthermore, there were no significant differences in the SOD, CAT, and GPx activities of the control and IR+Q group. A reduction of GSH and GSSGR levels in IR and IR+Q groups was detected but no significant differences were found between these groups. This study stresses that high concentration of ROS leads to renal ischemia and reperfusion, and quercetin reduces the renal injury by preventing the oxidative stress dependent on ischemia and reperfusion. Quercetin may be used in renal transplantation as an antioxidant drug.     

Enhanced oxidative stress in kidneys of salt-sensitive hypertension: role of sensory nerves

To determine the mechanism(s) underlying enhanced oxidative stress in kidneys of salt-sensitive hypertension, neonatal Wistar rats were given vehicle or capsaicin (CAP, 50 mg/kg sc) on the first and second days of life. After being weaned, male rats were assigned into four groups and treated for 2 wk with the following: vehicle + a normal sodium diet (NS, 0.4%, CON-NS), vehicle + a high-sodium diet (HS, 4%, CON-HS), CAP + NS (CAP-NS), and CAP + HS (CAP-HS). Systolic blood pressure was significantly increased in CAP-HS but not CAP-NS or CON-HS rats. Plasma and urinary 8-iso-prostaglandin F(2alpha) levels increased by approximately 40% in CON-HS and CAP-HS rats compared with their respective controls fed a NS diet (P < 0.05), and these parameters were higher in CAP-HS compared with CON-HS rats. Superoxide (O(2)(-)*) levels in the renal cortex and medulla increased by approximately 45% in CAP-HS compared with CON-HS, CON-NS, and CAP-NS rats (P < 0.05). Enhanced O(2)(-)* levels in the cortex and medulla in CAP-HS rats were prevented by preincubation of renal tissues with apocynin, a selective NAD(P)H oxidase inhibitor. Protein expression of NAD(P)H oxidase subunits, including p47(phox) and gp91(phox) in the renal cortex and medulla, was significantly increased in CAP-HS compared with CON-HS, CON-NS, and CAP-NS rats. In contrast, protein expression and activities of Cu/Zn SOD and Mn SOD were significantly increased in the renal medulla in both CAP-HS and CON-HS but in the cortex in CAP-HS rats only. Creatinine clearance decreased by approximately 45% in CAP-HS rats compared with CON-HS, CON-NS, and CAP-NS rats (P < 0.05). O(2)(-)* levels in the renal cortex of CAP-HS rats negatively correlated with creatinine clearance (r = -0.76; P < 0.001). Therefore, regardless of enhanced SOD activity to suppress oxidative stress, increased oxidative stress in the kidney of CAP-treated rats fed a HS diet is likely the result of increased expression and activities of NAD(P)H oxidase, which may contribute to decreased renal function and increased blood pressure in these rats. Our results suggest that sensory nerves may play a compensatory role in attenuating renal oxidative stress during HS intake.     

Effects of Greek legume plant extracts on xanthine oxidase,catalase and superoxide dismutase activities

Legumes are considered to have beneficial health implications, which have been attributed to their phytochemical content. Polyphenols are considered the most important phytochemical compounds extensively studied for their antioxidant properties. The aim of the present study was to examine the effects of potent antioxidant legume plant extracts on xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) activities. XO exerts a dual role, as it is the major contributor of free radicals during exercise while it generates uric acid, the most potent antioxidant molecule in plasma. CAT and SOD are two of the main enzymes of the antioxidant defence of tissues. We demonstrate that the majority of the extracts inhibited XO activity, but they had no effect on CAT inhibition and SOD induction when used at low concentrations. These results imply that the tested extracts may be considered as possible source of novel XO inhibitors. However, we have shown that allopurinol administration, a known XO inhibitor, before exercise reduces performance and induces oxidative stress in rats. Considering the fact that the extracts examined had an inhibitory effect on XO activity, possibly posing a restriction in their characterization as antioxidants, phytochemical antioxidant administration before exercise should probably be reconsidered.     

Benfotiamine Enhances Antioxidant Defenses and Protects against Cisplatin‐Induced DNA Damage in Nephrotoxic Rats

The objective of the present study was to assess superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), paraoxonase (PON1), glutathione reductase (GR), and catalase (CAT) activities ratio and their relationship with DNA oxidative damage in rats treated with cisplatin (3 mg/kg bwt/day) in the presence and absence of benfotiamine (100 mg/kg/day) for 25 days. Cisplatin‐induced renal damage was evidenced by renal dysfunction and elevated oxidative stress markers. SOD activity and levels of nitric oxide, protein carbonyl, malondialdehyde, and 8‐hydroxy‐2'‐deoxyguanosine were significantly increased by cisplatin treatment. Moreover, the ratios of GPx/GR, SOD/GPx, SOD/CAT, and SOD/PON1 were significantly increased compared to control. In contrast, glutathione levels were significantly decreased by cisplatin treatment. Simultaneous treatment of rats with cisplatin and benfotiamine ameliorate these variables to values near to those of control rats. This study suggests that benfotiamine can prevent cisplatin‐induced nephrotoxicity by inhibiting formation reactive species of oxygen and nitrogen. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:398‐405, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21501     

Enhancing effect of rasagiline on superoxide dismutase and catalase activities in the dopaminergic system in the rat

Rasagiline [N-propargyl-l(R)-aminoindan] is a selective irreversible MAO-B inhibitor as is (-)deprenyl. The effect of the drug on antioxidant enzyme activities on dopaminergic tissue was examined in male F-344 rats (8.5-months-old). Two experimental groups were infused subcutaneously with rasagiline saline solutions by means of osmotic minipumps implanted subcutaneously in the back of the rats. Control animals were also similarly implanted with saline filled mini-pumps. Three-and-one-half weeks later, animals were sacrificed and selected tissue samples removed from brain, kidney and heart. Two doses of rasagiline (0.5 mg/kg/day, 1.0 mg/kg/day, both for 3.5 weeks) significantly increased catalase activities about 2-fold in substantia nigra and striatum but not in hippocampus. Interestingly, in both renal cortex and medulla. catalase (CAT) activities were significantly increased. Both Mn- and Cu,Zn-superoxide dismutase (SOD) activities were increased 2 to 4 fold in substantia nigra, striatum and renal cortex and heart. Several groups, including our own have reported an extension of survival of deprenyl-treated animals of different species. Although the mechanism(s) of the life extension by deprenyl remains unresolved, it would be interesting to investigate the effect of rasagiline on the survival of animals, since deprenyl also was shown to increase antioxidant enzyme activities in brain dopaminergic regions.     

Protection against cisplatin-induced nephrotoxicity by Cu(II)2(3,5-diisopropylsalicylate)4

The ability of Cu(II)(2)(3,5-diisopropylsalicylate)(4), CuDIPS, which exhibits superoxide dismutase (SOD)-like activity, to prevent cisplatin-induced nephrotoxicity was examined in rats. Rats were divided into four groups and treated as follows: (i) vehicle control; (ii) cisplatin (16 mg/kg, intraperitoneally); (iii) CuDIPS (10 mg/kg, intraperitoneally); and (iv) cisplatin plus CuDIPS. Rats were sacrificed 3 days post-treatment. Cisplatin alone resulted in significantly increased plasma creatinine and urea. Administration of 10 mg/kg CuDIPS prevented the cisplatin-induced elevation of plasma creatinine and urea and protected against kidney damage. Relative to controls, rats that received cisplatin treatment displayed a decrease of reduced glutathione (GSH) and elevated platinum and thiobarbituric acid reactive substances (TBARS) levels in the kidney. In comparison with controls, activities of antioxidant enzymes (SOD, CAT, GSH-Px and GSH-Rd) were also reduced in the kidney of rats treated with cisplatin. Administration of 10 mg/kg CuDIPS prevented cisplatin-induced alterations in renal platinum, GSH, TBARS, and antioxidant enzyme activities. This study suggests that the protection offered by CuDIPS against cisplatin-induced nephrotoxicity is partly related to maintenance of renal antioxidant systems.     

Seed‐specific overexpression of antioxidant genes in Arabidopsis enhances oxidative stress tolerance during germination and early seedling growth

Enzymatic and non‐enzymatic antioxidants play important roles in the tolerance of abiotic stress. To increase the resistance of seeds to oxidative stress, At2S3 promoter from Arabidopsis was used to achieve overexpression of the antioxidants in a seed‐specific manner. This promoter was shown to be capable of driving the target gene to have a high level of expression in seed‐related organs, including siliques, mature seeds, and early seedlings, thus making its molecular farming applications in plants possible. Subsequently, genes encoding Mn‐superoxide dismutase (MSD1), catalase (CAT1), and homogentisate phytyltransferase (HPT1, responsible for the first committed reaction in the tocopherol biosynthesis pathway) were overexpressed in Arabidopsis under the control of the At2S3 promoter. Double overexpressers co‐expressing two enzymes and triple overexpressers were produced by cross pollination. Mn‐SOD and total CAT activities, as well as γ‐tocopherol content, significantly increased in the corresponding overproduction lines. Moreover, single MSD1‐transgene, double, and triple overexpressers displayed remarkably enhanced oxidative stress tolerance compared to wild type during seed germination and early seedling growth. Interestingly, an increase in the total CAT activity was also observed in the single MSD1‐transgenic lines as a result of MSD1 overexpression. Together, the combined increase in Mn‐SOD and CAT activities in seeds plays an essential role in the improvement of antioxidant capacity at early developmental stage in Arabidopsis.     

Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

Humans are systemically exposed to persistent organic pollutants, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has become a major environmental concern. Exposure to TCDD results in a wide variety of adverse health effects which is mediated by oxidative stress through CYP1A1 activation and arachidonic acid metabolites. Eicosapentaenoic acid (EPA) exhibits antioxidant property and competes with arachidonic acid in membrane phospholipids and produces anti-inflammatory EPA derivatives. Since both EPA and its derivatives have been reported to enhance the antioxidant mechanism, the present study aimed at studying whether EPA could offer protection against TCDD-induced oxidative stress and nephrotoxicity in Wistar rats. Estimation of kidney markers (serum urea and creatinine) and histopathological studies revealed that EPA treatment significantly reduced TCDD-induced renal damage. TCDD-induced oxidative damage was reflected in a significant increase in CYP1A1 activity and lipid peroxide levels with a concomitant decline in non-enzymic antioxidant (GSH) and various enzymic antioxidants such catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and glutathione peroxidase (GPx). In addition, TCDD-induced oxidative stress also resulted in decline in Na⁺-K⁺ and Mg²⁺ATPases activities with increase in Ca²⁺ ATPases activity. Oral treatment with EPA showed a significant cytoprotection against TCDD-induced renal oxidative stress by decreased CYP1A1 activity and enhanced antioxidant status. TCDD-induced alterations in ATPase enzyme activities were also prevented by EPA treatment. Our results show clear evidence that EPA ameliorates TCDD-induced oxidative stress and kidney damage; thus suggest the potential of EPA as an effective therapeutic agent against toxic effects mediated through redox imbalance.     

Modulation of Antioxidant Enzyme Expression by PTU-Induced Hypothyroidism in Cerebral Cortex of Postnatal Rat Brain

This study aimed to elucidate the effect of 6-n-propylthiouracil (PTU)-induced hypothyroidism on oxidative stress parameters and expression of antioxidant enzymes in cerebral cortex of rat brain during postnatal development. A significant decrease in levels of lipid peroxidation and H₂O₂ were seen in 7 and 30 days old PTU-treated rats with respect to their controls. Significantly decreased activities of superoxide dismutase (SOD) and catalase (CAT) along with the translated products of SOD1 and SOD2 were observed in 7, 15 and 30 days old PTU-treated rats as compared to their respective controls. However, increase in translated product of CAT was seen in all age groups of PTU-treated rats. Glutathione peroxidase activity was decreased in 7 days and increased in 15 days old PTU-treated rats with respect to their control groups. Histological sections clearly show a decline in neuronal migration with neurons packed together in the hypothyroid group as compared to the control.     

Biochemical effects of pretreatment with vitamins E and C in rats submitted to intrastriatal hypoxanthine administration

We previously demonstrated that intrastriatal injection of hypoxanthine, the major metabolite accumulating in Lesch-Nyhan disease, inhibited Na+,K+-ATPase activity and induced oxidative stress in rat striatum. In the present study, we evaluated the action of vitamins E and C on the biochemical alteration induced by hypoxanthine administration on Na+,K+-ATPase, TBARS, TRAP, as well as on superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx) activities in striatum of adult rats. Animals received pretreatment with vitamins E and C or saline during 7 days. Twelve hours after the last injection of vitamins or saline, animals were divided into two groups: (1) vehicle-injected group and (2) hypoxanthine-injected group. For all parameters investigated in this research, animals were sacrificed 30 min after drug infusion. Results showed that pretreatment with vitamins E and C prevented hypoxanthine-mediated effects on Na+,K+-ATPase, TBARS and antioxidant enzymes (SOD, CAT and GPx) activities; however the reduction on TRAP was not prevented by these vitamins. Although extrapolation of findings from animal experiments to humans is difficult, it is conceivable that these vitamins might serve as an adjuvant therapy in order to avoid progression of striatal damage in patients affected by Lesch-Nyhan disease.     

Acute exposure to the vinyl chalcogenide 3‐methyl‐1‐phenyl‐2‐(phenylseleno)oct‐2‐en‐1‐one induces oxidative stress in different brain area of rats

The mechanisms that lead to the onset of organoselenium intoxication are still poorly understood. Therefore, in the present study, we investigated the effect of acute administration of 3‐methyl‐1‐phenyl‐2‐(phenylseleno)oct‐2‐en‐1‐one on some parameters of oxidative stress and on the activity of creatine kinase (CK) in different brain areas and on the behaviour in the open field test of 90‐day‐old male rats. Animals (n = 10/group) were treated intraperitoneally with a single dose of the organoselenium (125, 250 or 500 µg kg^?1), and after 1 h of the drug administration, they were exposed to the open field test, and behaviour parameters were recorded. Immediately after they were euthanized, cerebral cortex, hippocampus and cerebellum were dissected for measurement of thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD) and CK activity. Our results showed that the dose of 500 µg kg^?1 of the organoselenium increased the locomotion and rearing behaviours in the open field test. Moreover, the organochalcogen enhanced TBARS in the cerebral cortex and cerebellum and increased the oxidation of proteins (carbonyl) only in the cerebral cortex. Sulfhydryl content was reduced in all brain areas, CAT activity enhanced in the hippocampus and reduced in the cerebellum and SOD activity increased in all brain structures. The organoselenium also inhibited CK activity in the cerebral cortex. Therefore, changes in motor behaviour, redox state and energy homeostasis in rats treated acutely with organoselenium support the hypotheses that the brain is a potential target for the organochalcogen action. Copyright © 2014 John Wiley & Sons, Ltd.     

Protective effect of brown Brazilian propolis against acute vaginal lesions caused by herpes simplex virus type 2 in mice: involvement of antioxidant and anti‐inflammatory mechanisms

Propolis has been highlighted for its antioxidant, anti‐inflammatory and antiviral properties. The purpose of this study was to investigate if brown Brazilian hydroalcoholic propolis extract (HPE) protects against vaginal lesions caused by herpes simplex virus type 2 (HSV‐2) in female BALB/c mice. The treatment was divided in 5 days of pre‐treatment with HPE [50 mg·kg^–1, once a day, intragastric (i.g.)], HSV‐2 infection [10 µl of a solution 1 × 10² plaque‐forming unit (PFU·ml^–1 HSV‐2), intravaginal inoculation at day 6] and post‐treatment with HPE (50 mg·kg^–1) for 5 days more. At day 11, the animals were killed, and the in vivo analysis (score of lesions) and ex vivo analysis [haematological and histological evaluation; superoxide dismutase (SOD), catalase (CAT) and myeloperoxidase (MPO) activities; reactive species (RS), tyrosine nitration levels, non‐protein thiols (NPSH) and ascorbic acid (AA) levels] were carried out. HPE treatment reduced extravaginal lesions and the histological damage caused by HSV‐2 infection in vaginal tissues of animals. HPE was able to decrease RS, tyrosine nitration, AA levels and MPO activity. Also, it protected against the inhibition of CAT activity in vaginal tissues of mice. HPE promoted protective effect on HSV‐2 infected animals by acting on inflammatory and oxidative processes, and this effect probably is caused by its antioxidant and anti‐inflammatory properties. Copyright © 2011 John Wiley & Sons, Ltd.     

Melatonin treatment for prevention of oxidative stress: involving histopathological changes

This study was undertaken to test the effect of irradiation on the histopathology of the hypothalamus and cerebral cortex. In addition, the probable effects of radiotherapy on the activities of antioxidant enzymes and levels of nitric oxide (NO) in the plasma were investigated as well. The effects of melatonin treatment on radiotherapy-based central nervous system (CNS) damage were also studied. For this purpose, the rats were randomized into four groups. The first group was the control group (sham-exposed group), the second group received only melatonin, the third group was irradiated and the fourth group received both melatonin and irradiation. Plasma samples of rats were collected for measuring the activities of superoxide dismutase (SOD), catalase (CAT) and the levels of NO. 24 h after the interventions, tissue samples were obtained from the hypothalamus and the cerebral cortex for the light microscopic investigations. These tissues were mostly affected by radiation. The results indicated that the application of radiation significantly enhanced the levels of plasma SOD and NO. On the other hand, melatonin pretreatment prevented the decrease in plasma CAT activity induced by irradiation. It was found that the application of melatonin could significantly prevent the irradiation-induced damages. Light microscopic results revealed that the damage of the CNS by radiation was prevented by the application of melatonin.     

Resveratrol delay the cataract formation against naphthalene‐induced experimental cataract in the albino rats

Oxidative stress‐induced toxicity plays a major role in ocular diseases such as retinal degeneration, age‐related cataract (ARC) formation and macular dystrophy. In this study, we explored the possible role of resveratrol (RSV) at the different dose levels (10, 20 and 40 mg/kg/day, ip) in an experimental model of naphthalene (1 g/kg/day, po)‐induced age‐related cataracts. Morphological changes in the eyes of the rats in two groups, the RSV and the ARC groups, were monitored weekly, and biochemical parameters in the lenses were assessed after completion of the experimental work. A comparison between the rats in the two groups showed that treatments at RSV doses of 20 and 40 mg/kg/day significantly retarded lenticular opacity, restored antioxidants (CAT, SOD, GPX, GSH), Ca²⁺ ATPase function, and protein contents, and reduced lipid peroxidation in the lenses of the animals in the RSV group. The treatment with resveratrol at a dose of 10 mg/kg/day did not show any anti‐cataractogenic effects. Based on the results of our investigation, we conclude that supplemental doses of resveratrol at 40 mg/kg/day effectively prevent cataract formation associated with the aging via increased soluble protein contents and Ca²⁺ homeostasis, apart from the antioxidant restoration. The results demonstrate that RSV treatment may be considered as a promising preventive or supplemental measure for delaying and/or preventing the formation of ARCs.     

The effect of one year's swimming exercise on oxidant stress and antioxidant capacity in aged rats

The effect of exercise on oxidant stress and on alterations in antioxidant defense in elderly has been investigated extensively. However, the impact of regularly performed long-term physical activity starting from adulthood and prolonged up to the old age is not yet clear. We have investigated the changes in the activities of antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) - and lipid peroxidation in various tissues of rats which had performed (old-trained) or had not performed (old-control) regular swimming exercise for one year. These animals were compared with young-sedentary rats. Increased lipid peroxidation was observed with ageing in all tissues (heart, liver, kidney, striated muscle) and swimming had no additional effect on this elevation of lipid peroxidation. Heart and striated muscle SOD activites, and striated muscle CAT activity increased as a consequence of ageing, whereas kidney and liver CAT activities, as well as GPx activities in kidney, liver, lung and heart were significantly decreased compared to young controls. Lung and heart SOD, liver CAT activities as well as GPx activities in liver, lung and heart were increased significantly in rats which performed exercise during ageing, compared to the old-control group. These findings suggest that lifelong exercise can improve the antioxidant defense in many tissues without constituting any additional oxidant stress.     

Naringenin attenuates cisplatin nephrotoxicity in rats

The effect of naringenin (NAR), a naturally occurring citrus flavanone, on the acute nephrotoxicity produced by cisplatin (7 mg/kg, i.v.) was investigated in the rat. Oral administration of NAR (20 mg/kg/day) for 10 days, starting 5 days before cisplatin single i.v. injection, produced significant protection of renal function. NAR reduced the extent of cisplatin-induced nephrotoxicity, as evidenced by significant reduction in serum urea and creatinine concentrations, decreased polyuria, reduction in body weight loss, marked reduction in urinary fractional sodium excretion and glutathione S-transferase (GST) activity, and increased creatinine clearance. Cisplatin-induced alterations in renal cortex lipid peroxides and GST activity were markedly improved by NAR. Cisplatin-induced alterations in renal cortex antioxidant defense system were greatly prevented by NAR. In cisplatin-NAR combined treatment group, antioxidant enzymes namely superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were significantly increased to 54.5, 30.3 and 35.6%, respectively compared to cisplatin treated group. Platinum renal content was not affected by NAR treatment. The results provide further insight into the mechanisms of cisplatin-induced nephrotoxicity and confirm the antioxidant potential of NAR.