Oxidative stress in the brain of reproductive male rats during aging

Reproduction alters the male physiology. We performed a comprehensive study to examine oxidative stress in the brains of male rats with (experienced) or without (naïve) reproductive activity during aging. Oxidative stress was assessed by measuring the activity of catalase, glutathione peroxidase, superoxide dismutase, glutathione S-transferase, aconitase, and aconitase reactivated, and by measuring lipid peroxidation, protein carbonylation, nitrite and nitrate levels, vitamin C levels, and glutathione (total, reduced, oxidized forms) levels in brain tissue, as well as testosterone and estradiol levels in serum. Reproductively active animals exhibited increased testosterone levels and aconitase activity, suggesting an increased metabolism. Increased antioxidant enzyme activities and increased levels of antioxidant compounds were observed, yet damage to biomolecules was also observed in experienced rats. During aging changes in oxidative stress were observed. We found higher activities of antioxidant enzymes, higher amounts of antioxidants, and more damage at six months of age among experienced animals than among naïve animals. Similar antioxidant activities and levels, and damage were found between the groups at twenty-four months of age. These results add comprehensive data regarding changes in oxidative stress during aging, and suggest an explanation for the costs of reproduction.     

Oxidative stress in the kidney of reproductive female rats during aging

Reproduction is a costly life process, and the reproductive investment by females appears to be greater than males in many species. We have analyzed the effects of reproductive investment during aging with respect to oxidative stress parameters in female Wistar rats. We measured the activity glutathione peroxidase, glutathione S-transferase, superoxide dismutase, consumption of hydrogen peroxide, protein carbonylation, lipid peroxidation, nitrite and nitrate levels, and Vitamin C (Vit. C) and E levels. We traced oxidative profiles at ages 3, 6, 12, and 24 months. Animals were grouped according to reproductive experience: experienced or naive with respect to reproductive activity. We measured aconitase activity and sex hormone levels. The naive animals exhibited an increase with respect to experienced in most parameters studied at 6 and 24 months, whereas experienced animals exhibited a similar increase at 3 and 12 months. At 6 months of age, during the period that would represent peak reproductive activity, naive animals showed higher levels of MDA, Vit. C, consumption of hydrogen peroxide and GPx, aconitase, and SOD activities. In naive elderly rats, we observed an increase in oxidative damage markers and an increase in enzymatic and non-enzymatic antioxidants, with the exception of consumption of hydrogen peroxide and Vit. C. In the long term, the reproductive investment was not sufficient to interfere with antioxidant capacity, and did not contribute to oxidative damage in kidneys of female Wistar rats.     

Cordycepin (3′-deoxyadenosine) attenuates age-related oxidative stress and ameliorates antioxidant capacity in rats

Free radical-induced oxidative damage is considered to be the most important consequence of the aging process. The activities and capacities of antioxidant systems of cells decline with increased age, leading to the gradual loss of pro-oxidant/antioxidant balance and resulting in increased oxidative stress. Our investigation was focused on the effects of cordycepin (3′-deoxyadenosine) on lipid peroxidation and antioxidation in aged rats. Age-associated decline in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced glutathione (GSH), vitamin C and vitamin E, and elevated levels of malondialdehyde (MDA) were observed in the liver, kidneys, heart and lungs of aged rats, when compared to young rats. Furthermore, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine were found to be significantly elevated in aged rats compared to young rats. Aged rats receiving cordycepin treatment show increased activity of SOD, CAT, GPx, GR and GST, and elevated levels of GSH, and vitamins C and E such that the values of most of these parameters did not differ significantly from those found in young rats. In addition, the levels of MDA, AST, ALT, urea and creatinine became reduced upon administration of cordycepin to aged rats. These results suggest that cordycepin is effective for restoring antioxidant status and decreasing lipid peroxidation in aged rats.     

Moderate exercise with a dietary vitamin C and e combination protects against streptozotocin-induced oxidative damage to the kidney and lens in pregnant rats.

Moderate exercise and vitamin C and E (VCE) supplementation can be beneficial to diabetes due to reducing free radical production in lens and kidney of diabetic pregnant rats. We investigated the effect of VCE supplementation and moderate exercise on lipid peroxidation (MDA) and scavenging enzyme activity in the kidneys and lens of STZ-induced diabetic pregnant rats. Fifty female Wistar rats were used and were randomly divided into five groups. First and second were used as the control and pregnant control group. Third group was the pregnant diabetic group. The fourth group was the diabetic-pregnant-exercise group. VCE-supplemented feed was given to pregnant-diabetic-exercise rats constituting the fifth group. Animals in the exercised groups were moderately exercised daily on a treadmill (16.1 m/min, 45 min/d) for three weeks (five days a week). Diabetes was induced on day zero of the study. Plasma, lens, and kidney samples were taken from all animals on day 20. Exercise and administration of VCE to pregnant diabetic rats resulted in significant decrease in the albumin and total protein values and the elevated MDA, plasma creatinine, and urea levels as an indicator of oxidative stress and renal functional parameters. Exercise and VCE supplementation also increased glutathione peroxidase (GSH-Px), reduced glutathione (GSH), vitamin E, and beta-carotene levels in the kidney, GSH-Px and GSH in the lens, the albumin and total protein values in plasma. In the diabetic pregnant animals, the decreased vitamins A and E concentration and GSH levels in kidney, creatinine, and urea values in plasma did not improve through exercise only although their concentrations were increased by VCE supplementation. Kidney weight did not also affect either by exercise or VCE supplementation. In conclusion, these results suggest that exercise plus VCE affects antioxidant metabolism and reduces lipid peroxidation, thereby improving the damage caused by oxidative stress involved in the pathogenesis of lens and kidney in diabetic pregnant rats. Moderate exercise with dietary VCE may play a role in preventing nephropathy and cataract formation in diabetic pregnant rat.     

The role of glutathione S- transferase M1 and T1 gene polymorphisms and oxidative stress-related parameters in Egyptian patients with essential hypertension

BackgroundEssential hypertension is a complex, multifactorial, polygenic disease in which the underlying genetic components remain unknown. Glutathione S-transferase (GST) enzyme is involved in detoxification of reactive oxygen species. This study aimed to investigate GSTM1 and GSTT1 gene polymorphisms in Egyptian essential hypertensive patients and their relationship with oxidative stress-related parameters.MethodsThe study included 40 newly-diagnosed, untreated, essential hypertensive patients and 40 normotensive subjects. Plasma levels of malondialdehyde (MDA), and nitrate/nitrite and erythrocyte reduced glutathione (GSH), activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione S-transferase (GST) were measured. Genotyping for GSTM1 and GSTT1 was performed.ResultsThe frequency of GSTM1+ve/GSTT1+ve in hypertensives (5%) was lower than in normotensives (37.5%).The frequency of GSTM1?ve/GSTT1?ve was elevated in hypertensives (35%) as compared to normotensives (7.5%). Plasma MDA was higher and nitrate/nitrite was lower in hypertensives than in normotensives. Erythrocyte GSH, activities of CAT, SOD, GSH-Px, and GST of hypertensives were lower than normotensives. Moreover, GST activity was lower in subjects with GSTM1?ve/GSTT1?ve than in those with GSTM1+ve/GSTT1+ve. In hypertensives, both systolic and diastolic blood pressures were negatively correlated with activities of CAT, GSH-Px, and GST.ConclusionsGSTM1?ve/GSTT1?ve is a potential genetic factor to predict development of essential hypertension and permit early therapeutic intervention. The significant association between blood pressure and oxidative stress-related parameters indicates the pathogenic role of oxidative stress in hypertension. Antioxidants could be useful in the management of essential hypertension to prevent progressive deterioration and target organ damage however, further studies involving long-term clinical trials may help to assess the efficacy of these therapeutic agents.     

Characterization of oxidative stress in various tissues of diabetic and galactose-fed rats

Rats fed a galactose-rich diet have been used for several years as a model for diabetes to study, particularly in the eye, the effects of excess blood hexoses. This study sought to determine the utility of galactosemia as a model for oxidative stress in extraocular tissues by examining biomarkers of oxidative stress in galactose-fed rats and experimentally-induced diabetic rats. Sprague-Dawley rats were divided into four groups: experimental control; streptozotocin-induced diabetic; insulin-treated diabetic; and galactose-fed. The rats were maintained on these regimens for 30 days, at which point the activities of catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase, as well as levels of lipid peroxidation and reduced and oxidized glutathione were determined in heart, liver, and kidney. This study indicates that while there are some similarities between galactosemic and diabetic rats in these measured indices of oxidative stress (hepatic catalase activity levels and hepatic and renal levels of oxidized glutathione in both diabetic and galactosemic rats were significantly decreased when compared to normal), overall the galactosemic rat model is not closely parallel to the diabetic rat model in extra-ocular tissues. In addition, several effects of diabetes (increased hepatic glutathione peroxidase activity, increased superoxide dismutase activity in kidney and heart, decreased renal and increased cardiac catalase activity) were not mimicked in galactosemic rats, and glutathione concentration in both liver and heart was affected in opposite ways in diabetic rats and galactose-fed rats. Insulin treatment reversed/prevented the activity changes in renal and cardiac superoxide dismutase, renal and cardiac catalase, and hepatic glutathione peroxidase as well as the hepatic changes in lipid peroxidation and reduced and oxidized glutathione, and the increase in cardiac glutathione. Thus, prudence should be exercised in the use of experimentally galactosemic rats as a model for diabetes until the correspondence of the models has been more fully characterized.     

Alterations of antioxidant enzymes and oxidative stress markers in aging

In accordance with the present state of scientific knowledge, the excessive production of free radicals in the organism, and the imbalance between the concentrations of these and the antioxidant defenses may be related to processes such as aging and several diseases. The aging process has been described by various theories. In particular, the free radical theory of aging has received widespread attention which proposes that deleterious actions of free radicals are responsible for the functional deterioration associated with aging. Although, the relationship between lipid peroxidation and aging have been investigated extensively, the studies have produced conflicting results. To investigate the correlation between the oxidative stress and aging, we have determined the levels of lipid peroxidation expressed as thiobarbituric acid reactive substances (TBARS; MDA) and conjugated dien; oxidative protein damage as indicated by carbonyl content and activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in a sample of 100 healthy men and women ranging in age from 20 to 70years. In addition, vitamin E, C levels, reduced glutathione and sulphydryl content were determined. The oxidation end product of nitric oxide (nitrate) was also studied to investigate any role of nitrogen radicals in aging. Our data show that there is an age related increase in lipid peroxidation expressed as MDA and oxidative protein damage as indicated by carbonyl content. Aging is not linked to a decline in antioxidant enzymes except GPx. Our data suggests that the level of oxidative stress increase cannot entirely be attributed to a decrease in the activities of antioxidant defense system and probably various factors may contribute to this process.     

Lipid peroxidation and free radical scavengers in thyroid dysfunction in the rat: a possible mechanism of injury to heart and skeletal muscle in hyperthyroidism

This study was designed to determine if peroxidation of biomembrane lipid and the protective system can be modified by the change in oxidative metabolism induced by thyroid dysfunction. The free radical scavengers (i.e. cuprozinc cytosolic and mangano mitochondrial superoxide dismutases, glutathione peroxidase, and catalase), mitochondrial oxidative marker enzymes (cytochrome c oxidase and fumarase), and lipid peroxide were measured in liver, heart, soleus (slow oxidative), and extensor digitorum longus (fast glycolytic) muscles. Rats were rendered hyper- or hypothyroid for 4 weeks and then killed. Superoxide dismutases were detected by specific RIAs: catalase by polarography, and lipid peroxide by fluorimetry. Hypothyroid rats failed to grow, while hyperthyroid rats had hypertrophied hearts but no growth failure. An increase in lipid peroxide was observed in the soleus and heart muscles of hyperthyroid rats. This was accompanied by an increase in mitochondrial superoxide dismutase and oxidative markers. No such change was observed in either fast glycolytic muscle or liver. Glutathione peroxidase decreased in all tissues of hyperthyroid rats, and there was a parallel decrease in catalase in most tissues. On the other hand, hypothyroidism induced a reduction in oxidative markers and mitochondrial superoxide dismutase in heart and skeletal muscles, but only a marginal change in lipid peroxidation. The cytosolic superoxide dismutase did not change in relation to either oxidative metabolism or lipid peroxidation. These results suggest that the enhanced oxidative metabolism and decreased glutathione peroxidase in hyperthyroidism result in an increase in lipid peroxidation and, in slow oxidative and heart muscle, possible organ damage. No adverse reaction mediated by active oxygen species was found in hypothyroid rat tissues.     

Hepatoprotective effect of the aqueous extract of the roots of Decalepis hamiltonii against ethanol-induced oxidative stress in rats.

The hepatoprotective activity of the aqueous extract of the roots of Decalepis hamiltonii was investigated against ethanol-induced oxidative stress and liver damage. Pretreatment of rats with aqueous extract of the roots of D. hamiltonii, single (50, 100 and 200mg/kg b.w.) and multiple doses (50 and 100mg/kg b.w. for 7 days) significantly prevented the ethanol (5g/kg b.w.) induced increases in the activities of the serum enzymes, aspartate and alanine transaminases, alkaline phosphatase and lactate dehydrogenase in a dose dependent manner. Parallel to these changes, the root extract inhibited the ethanol-induced oxidative stress in the liver by suppressing lipid peroxidation and protein carbonylation and maintaining the levels of antioxidant enzymes and glutathione. The biochemical changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the root extract. The protective effect of the root extract against hepatotoxicity of alcohol was more pronounced by the multiple dose pretreatment. Hepatoprotective activity of the aqueous extract of the roots of D. hamiltonii could be attributed to the antioxidant effect of the constituents and enhanced antioxidant defenses.     

Effects of hypoxia reoxygenation in brain slices from rats with type 1-like diabetes mellitus

BACKGROUND: The aim of this study was to determine whether the brain tissue of type 1 diabetic animals is more susceptible to damage by hypoxia reoxygenation than healthy animals. METHODS: This study used rats with diabetes of 1, 2 and 3 months (N = 15 rats/group). Brain slices were subjected to hypoxia and reoxygenation for 180 min in vitro. We measured oxidative stress (lipid peroxidation, glutathione concentration and enzyme activities related to glutathione), concentration of prostaglandin E(2) (PGE(2)) and nitric oxide (NO) pathway (nitrite + nitrate, activities of constitutive (cNOS) and inducible (iNOS) nitric oxide synthase). As a parameter of cell death we measured the efflux of lactate dehydrogenase (LDH). RESULTS: After reoxygenation LDH activity increased in comparison to nondiabetic animals by 40, 40.6 and 68.9% in animals with diabetes of 1, 2 and 3 months duration, respectively. These changes were accompanied by greater increases in lipid peroxides (25.4, 93.7 and 92.8%). PGE(2) accumulated in significantly larger amounts in diabetic animals (62.5, 85.5 and 114%), and nitrite + nitrate accumulation was significantly greater in rats with diabetes of 2 (40.2%) and 3 months duration (24.0%). iNOS activity increased significantly in all the groups of diabetic animals, with the largest increases in rats with diabetes of 2 (18.6%) and 3 months duration (21.1%). CONCLUSIONS: The biochemical pathways involved in oxidative stress and neuronal death are more sensitive to hypoxia reoxygenation in type 1-like diabetic, as compared to normal, rats.     

Comparative analysis of the protective effects of melatonin and vitamin E on streptozocin-induced diabetes mellitus

There is a clearly documented link between diabetic complications and lipid peroxidation. Hyperglycemia causes a reduction in levels of protective endogenous antioxidants and increases generation of free radicals. The present study was carried out to compare the protective effects of melatonin and vitamin E against streptozocin (STZ)-induced diabetes in rats. Melatonin was administered s.c. (100 microg/kg) whereas vitamin E was given i.p. (100 mg/kg) after induction of diabetes with STZ (60 mg/kg). Plasma total cholesterol, triglyceride and low density lipoprotein (LDL) levels were increased in STZ group while both melatonin and vitamin E injection caused a significant decrease in the levels of all these parameters. The lipid lowering effect of melatonin was greater than that of vitamin E. Melatonin caused a significant decrease in brain, liver and kidney tissue malondialdehyde (MDA) levels which were increased because of STZ-induced diabetes. Vitamin E also reduced elevated MDA concentrations in diabetic rat tissues, but the effect of melatonin was more potent than that of vitamin E. Furthermore, treatment of diabetic rats with melatonin increased brain and kidney glutathione peroxidase (GSH-Px) activity to the levels below that of control rats. Vitamin E was found to be less effective on GSH-Px activity levels in brain and kidney than melatonin whereas it was more potent than melatonin in liver. In summary, melatonin prevents many diabetic complications by reducing oxidative stress and protects organisms from oxidative damage and dyslipidemia. Considering the much lower molar concentration of melatonin compared with vitamin E, melatonin seems to be a more potent antioxidant, especially in the brain and kidney.     

The effect of carnosine treatment on prooxidant–antioxidant balance in liver,heart and brain tissues of male aged rats

Carnosine (β-alanyl-l-histidine) is a dipeptide with antioxidant properties. Oxidative damage by free radicals is one of the mechanisms underlying the aging process. This study was done to investigate the effects of carnosine treatment on lipid peroxidation and antioxidant status of liver, heart, brain in male young and aged rats. At the initiation of study, young and aged rats were 5 and 22 months old, respectively. Carnosine (250 mg/kg, daily, i.p.) was administered for 1 month to rats. At the end of this period, malondialdehyde (MDA) and diene conjugate (DC) and protein carbonyl (PC) levels, glutathione (GSH), vitamin E and vitamin C levels and Cu,Zn-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities were determined in tissues of carnosine-treated young and old rats. Liver and heart, but not brain MDA and DC levels increased significantly in aged rats as compared to young rats. Liver PC levels were also significantly elevated. Significant decreases in GSH and vitamin C levels and SOD activities were detected in liver of aged rats, but vitamin E levels and GSH-Px and GST activities remained unchanged. Non-enzymatic and enzymatic antioxidants did not change in heart and brain of aged rats. Carnosine treatment decreased high MDA, DC and PC levels and caused significant increases in vitamin E level and SOD activity in the liver of aged rats. There were no changes in non-enzymatic and enzymatic antioxidants in the heart and brain of carnosine-treated aged rats. In conclusion, carnosine treatment was found to be useful in the decrease of age-related oxidative stress in the liver.     

Mechanisms of isoproterenol‐induced cardiac mitochondrial damage: protective actions of melatonin

Mitochondrial dysfunction due to oxidative damage is the key feature of several diseases. We have earlier reported mitochondrial damage resulting from the generation of oxidative stress as a major pathophysiological effect of isoproterenol (ISO)‐induced myocardial ischemia in rats. That melatonin is an antioxidant that ameliorates oxidative stress in experimental animals as well as in humans is well established. We previously demonstrated that melatonin provides cardioprotection against ISO‐induced myocardial injury as a result of its antioxidant properties. The mechanism of ISO‐induced cardiac mitochondrial damage and protection by melatonin, however, remains to be elucidated in vitro. In this study, we provide evidence that ISO causes dysfunction of isolated goat heart mitochondria. Incubation of cardiac mitochondria with increasing concentrations of ISO decreased mitochondrial succinate dehydrogenase (SDH) activity, which plays a pivotal role in mitochondrial bioenergetics, as well as altered the activities of other key enzymes of the Kreb's cycle and the respiratory chain. Co‐incubation of ISO‐challenged mitochondria with melatonin prevented the alterations in enzyme activity. That these changes in mitochondrial energy metabolism were due to the perpetration of oxidative stress by ISO was evident from the increased levels of lipid peroxidation and decreased reduced glutathione/oxidized glutathione ratio. ISO‐induced oxidative stress also altered mitochondrial redox potential and brought about changes in the activity of the antioxidant enzymes manganese superoxide dismutase and glutathione peroxidase, eventually leading to alterations in total ATPase activity and membrane potential. Melatonin ameliorated these changes likely through its antioxidant abilities suggesting a possible mechanism of cardioprotection by this indole against ISO‐induced myocardial injury.     

Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats

AIM： To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vu/gare （FVE） on ethanol-induced gastric lesions in rats.
METHODS： FVE was administered by gavage at doses of 75, i50 and 300 mg/kg, and famotidine was used at the dose of20mg/kg.Following a 60 min period, all the rats were given 1 mL of ethanol （80%） by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated; whole blood malondialdehyde （MDA） and reduced glutathione （GSH）, serum nitrate, nitrite, ascorbic acid, retinol and β-carotene levels were measured in all the groups.
RESULTS： It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage. This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control （4.18 ± 2.81 vs 13.15 ± 4.08, P 〈 0.001）. Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid, retinol and β-carotene levels.
CONCLUSION： FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity.     

Effect of haemodialysis on the oxidative stress and antioxidants in diabetes mellitus

Abstract Oxidative stress has been defined as a loss of counterbalance between free radical or reactive oxygen species (ROS) production and antioxidant systems. It is involved in the pathogenesis of different chronic diseases. High levels of ROS production via different biochemical mechanisms accompany diseases like type 2 diabetes mellitus (DM) and end-stage renal disease (ESRD). Elevated oxidative status and reduced antioxidant defence systems in patients with DM and ESRD accelerate the prevalence of atherosclerosis and other chronic complications. Our aim was to reveal the effects of diabetes and haemodialysis (HD) separately and together on oxidative stress. In our study, we included 20 diabetic (DM) patients with no renal disease, 20 non-diabetic haemodialysis (HD), 20 diabetic haemodialysis (DHD) patients and 20 healthy volunteers. We have determined the levels of lipid peroxidation expressed as thiobarbituric acid-reactive substances (TBARS), oxidative protein damage as indicated by protein carbonyl (PCO) content and activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) in all patient groups and healthy subjects. We found enhanced oxidative stress in all patient groups due to an increase in lipid peroxidation (TBARS) and increased oxidative protein damage in terms of PCO content and reduced activities of SOD, CAT and GSH-Px. Oxidative stress was more profound in diabetic patients undergoing haemodialysis. We conclude that both diabetes and dialysis increase oxidative stress and their combined effect on oxidative stress is the highest in magnitude as observed in diabetic patients undergoing haemodialysis.     

Role of N-acetylcysteine on fibrosis and oxidative stress in cirrhotic rats

BACKGROUND: Hepatic cirrhosis is the final stage of liver dysfunction, characterized by diffuse fibrosis which is the main response to the liver injury. The inhalatory carbon tetrachloride is an effective experimental model that triggers cirrhosis and allows to obtain histological and physiological modifications similar to the one seen in humans. AIM: To investigate the effects of N-acetylcysteine (NAC) on the fibrosis and oxidative stress in the liver of cirrhotic rats, analyzing liver function tests, lipoperoxidation, activity of glutathione peroxidase enzyme, collagen quantification, histopathology, as well as the nitric oxide role. METHODS: The animals were randomly in three experimental groups: control (CO); cirrhotic (CCl4) and CCl4 + NAC. Evaluate the lipid peroxidation, the glutathione peroxidase enzyme, the collagen and the expression of inducible nitric oxide synthase (iNOS). RESULTS: The cirrhotic group treated with N-acetylcysteine showed trough the histological analysis and collagen quantification lower degrees of fibrosis. This group has also shown less damage to the cellular membranes, less decrease on the glutathione peroxidase levels and less expression of inducible nitric oxide synthase when matched with the cirrhotic group without treatment. CONCLUSION: N-acetylcysteine seams to offer protection against hepatic fibrosis and oxidative stress in cirrhotic rat livers.     

Differential indicators of diabetes-induced oxidative stress in New Zealand White rabbits: role of dietary vitamin E supplementation

Determination of reliable bioindicators of diabetes-induced oxidative stress and the role of dietary vitamin E supplementation were investigated. Blood (plasma) chemistries, lipid peroxidation (LPO), and antioxidant enzyme activities were measured over 12 weeks in New Zealand White rabbits (control, diabetic, and diabetic + vitamin E). Cholesterol and triglyceride levels did not correlate with diabetic state. Plasma LPO was influenced by diabetes and positively correlated with glucose concentration only, not cholesterol or triglycerides. Liver glutathione peroxidase (GPX) activity negatively correlated with glucose and triglyceride levels. Plasma and erythrocyte GPX activities positively correlated with glucose, cholesterol, and triglyceride concentrations. Liver superoxide dismutase activity positively correlated with glucose and cholesterol concentration. Vitamin E reduced plasma LPO, but did not affect the diabetic state. Thus, plasma LPO was the most reliable indicator of diabetes-induced oxidative stress. Antioxidant enzyme activities and types of reactive oxygen species generated were tissue dependent. Diabetes-induced oxidative stress is diminished by vitamin E supplementation.     

Oxidative Stress and DNA Single Strand Breaks in Skeletal Muscle of Aged Rats: Role of Carnitine and Lipoicacid

The exposure of biological system to various conditions of oxidative stress is the major contributor for aging process. Oxidative stress in turn increases the cellular levels of oxidatively modified proteins, lipids and nucleic acids resulting in a loss of physical activity and metabolic integrity. In this study, we evaluated the role of l-carnitine and dl-α-lipoic acid in minimizing oxidant generation and macromolecular damage in skeletal muscle of aged rats. We found that the oxidant generation was increased in aged rat skeletal muscle when compared to young rats. There was a simultaneous increase in the levels of lipid peroxidation, protein carbonyl content and DNA strand breaks in aged rat skeletal muscle. Administration of l-carnitine (300 mg/kg body wt/day) and dl-α-lipoic acid (100 mg/kg body wt/day) to aged rats for 30 days, decreased the oxidant generation, lipid peroxidation, protein carbonylation and DNA strand breaks. We concluded that co-administration of carnitine and lipoic acid to aged rats has the potential to prevent oxidative stress mediated macromolecular damage in skeletal muscle of aged rats by their putative role as efficient antioxidants.     

Melatonin, a pineal secretory product with antioxidant properties, protects against cisplatin-induced nephrotoxicity in rats

In an attempt to define the role of the pineal secretory melatonin and an analogue, 6-hydroxymelatonin (6-OHM), in limiting oxidative stress, the present study investigated the cisplatin (CP)-induced alteration in the renal antioxidant system and nephroprotection with the two indolamines. Melatonin (5 mg/kg), 6-OHM (5 mg/kg), or an equal volume of saline were administered intraperitoneally (i.p.) to male Sprague Dawley rats 30 min prior to an i.p. injection of CP (7 mg/kg). After CP treatment, the animals each received indolamine or saline every day and were sacrificed 3 or 5 days later and plasma as well as kidney were collected. Both plasma creatinine and blood urea nitrogen increased significantly following CP administration alone; these values decreased significantly with melatonin co-treatment of CP-treated rats. In the kidney, CP decreased the levels of GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio, an index directly related to oxidative stress. When animals were treated with melatonin, the reduction in the GSH/GSSG ratio was prevented. Treatment of CP-enhanced lipid peroxidation in the kidney was again prevented in animals treated with melatonin. The activity of the antioxidant enzyme, glutathione peroxidase (GSH-Px), decreased as a result of CP administration, which was restored to control levels with melatonin co-treatment. Upon histological analysis, damage to the proximal tubular cells was seen in the kidneys of CP-treated rats; these changes were prevented by melatonin treatment. 6-OHM has been shown to have some antioxidative capacity, however, the protective effects of 6-OHM against CP-induced nephrotoxicity were less than those of melatonin. The residual platinum concentration in the kidney of melatonin co-treated rats was significantly lower than that of rats treated with CP alone. It is concluded that administration of CP imposes a severe oxidative stress to renal tissue and melatonin confers protection against the oxidative damage associated with CP. This mechanism may be reasonably attributed to its radical scavenging activity, to its GSH-Px activating property, and/or to its regulatory activity for renal function.     

Perturbation of erythrocyte antioxidant barrier, lipid peroxidation and protein carbonylation in non-diabetic first degree relatives of patients with type 2 diabetes

OBJECTIVE: Oxidative stress plays an important role in the pathogenesis of type 2 diabetes. But it is still discussed whether oxidative stress precedes or merely reflects diabetic complications. The present study was carried out to search for the possibility of oxidative stress among the first degree relatives of patients with type 2 diabetes, as they are more prone to develop type 2 diabetes. METHODS: This study has been conducted on 30 first degree relatives of patients with type 2 diabetes and 34 healthy subjects without any known family history of diabetes. Whole blood glutathione, plasma malondialdehyde (MDA), protein carbonylation, fasting glucose levels and the activities of anti-oxidant enzymes glutathione peroxidase, catalase and glutathione S-transferase were measured. RESULTS: The antioxidant enzyme glutathione peroxidase, plasma MDA and protein carbonyl levels were significantly elevated in the test group compared with controls. The glutathione levels were significantly decreased in the test group. CONCLUSION: This study reveals alteration of antioxidant status and oxidative stress among the first degree relatives of patients with type 2 diabetes.