Effects of Buprenorphine on Balance of Oxidant/Antioxidant System in the Different Ages of Male Rat Liver

Our knowledge about a link between buprenorphine and hepatotoxicity is controversial. This study evaluated the effects of buprenorphine on the liver of young, adult, and aged rats. For this reason, young, adult, and aged rats received intraperitoneally 0.25, 0.5, and 1 mg/kg buprenorphine for 30 days. The present results revealed that the normal aging was associated with a significant decrease in the activities of antioxidant enzymes, and an increase in the liver lipid peroxidation, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities in the aged rats. This study also demonstrated that buprenorphine led to a significant increase in the serum activities of ALT, AST, and LDH as well as liver lipid peroxidation content with a decrease in the antioxidant enzymes in the liver of buprenorphine‐treated aged rat versus the aged matched control animals. In conclusion, the present results demonstrate that buprenorphine deteriorated oxidative damage in the aged livers.     

Influence of subacute treatment of some plant growth regulators on serum marker enzymes and erythrocyte and tissue antioxidant defense and lipid peroxidation in rats

This study aims to investigate the effects of the plant growth regulators (PGRs) (2,3,5-triiodobenzoic acid (TIBA), Naphthaleneacetic acid (NAA), and 2,4-dichlorofenoxyacetic acid (2,4-D)) on serum marker enzymes (aspartate aminotransferase (AST), alanin aminotransferase (ALT), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH)), antioxidant defense systems (reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST), and catalase (CAT)), and lipid peroxidation content (malondialdehyde = MDA) in various tissues of rats. 50 and 100 ppm of PGRs as drinking water were administered orally to rats (Sprague-Dawley albino) ad libitum for 25 days continuously. The PGRs treatment caused different effects on the serum marker enzymes, antioxidant defense systems, and the MDA content in experimented rats compared to controls. Results showed that TIBA caused a significant decrease in serum AST activity with both the dosage whereas serum CPK was significantly increased with 100 ppm dosage of TIBA. Meanwhile, serum AST, CPK, and LDH activities were significantly increased with both dosage of NAA and 2,4-D. The lipid peroxidation end-product MDA significantly increased in the all tissues treated with both dosages of PGRs without any change in the brain and erythrocyte of rats treated with both the dosages of 2,4-D. The GSH depletion in the kidney and brain tissues of rats treated with both dosages of PGRs was found to be significant. Furthermore, the GSH depletion in the erythrocyte of rats treated with both dosages of PGRs except 50 ppm dosage of 2,4-D was significant too. Also, the GSH level in the liver was significantly depleted with 50 ppm of 2,4-D and NAA, whereas the GSH depletion in the same tissue did not significantly change with the treatment. The activity of antioxidant enzymes was also seriously affected by PGRs; SOD significantly decreased in the liver, heart, kidney, and brain of rats treated with both dosages of NAA, whereas the SOD activity in the erythrocytes, liver, and heart was either significantly decreased or not changed with two doses of 2,4-D and TIBA. Although the CAT activity significantly increased in the erythrocyte and brain of rats treated with both doses of PGRs, it was not changed in the liver, heart, and kidney. Meanwhile, the ancillary enzyme GR activity significantly increased in the brain, heart, and liver but decreased in the erythrocyte and kidney of rats treated with both doses of PGRs. The drug-metabolizing enzyme GST activity significantly increased in the heart and kidney but decreased in the brain and erythrocytes of rats treated with both dosages of PGRs. As a conclusion, the results indicate that PGRs might affect antioxidant potential enzymes, the activity of hepatic damage enzymes, and lipid peroxidation dose independently. Also, the rats resisted to oxidative stress via antioxidant mechanism but the antioxidant mechanism could not prevent the increases in lipid peroxidation in rat's tissues. These data, along with the determined changes, suggest that PGRs produced substantial systemic organ toxicity in the erythrocyte, liver, brain, heart, and kidney during the period of a 25-day subacute exposure.     

Effect of cigarette smoke on lipid peroxidation and antioxidant enzymes in albino rat

Effect of cigarette smoke on lipid peroxidation (LPX) and antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione-S-transferase (GST) in various organs like brain, heart, lung, liver and kidney of the albino rats exposed to cigarette smoke for 30 min/day for a period of 30 days were assayed. It was observed that the lipid peroxide levels in liver, lung and kidney were enhanced in case of animals exposed to cigarette smoke, whereas brain and heart did not show any change as compared to control animals. The activity of the antioxidant enzymes was also elevated in liver, lung and kidney of the test animals whereas, brain and heart did not show any change in the activities of all of these antioxidant enzymes except glutathione-s-transferase which was increased in brain also. The level of reduced glutathione (GSH) was lowered in liver, lung and kidney of the tested animals when compared with the control animals but there was no significant change in brain and heart. The results of our study suggest that cigarette smoke induces lipid peroxidation in liver, lung and kidney, and the antioxidant enzymes levels were enhanced in order to protect these tissues against the deleterious effect of the oxygen derived free radicals. The depletion of reduced glutathione in these organs could be due to it's utilization by the tissues to mop off the free radicals.     

Study of heterocycle rings binding to human serum albumin

Doxorubicin continues to be one of the most widely used anticancer agents in the clinic despite its dose-limiting side-effects. Many of doxorubicin's dose-limiting toxicities occur due to its generation of toxic oxygen species, resulting in oxidative stress. Some clinical observations have suggested that doxorubicin may have greater toxicity in older patients. The studies presented here compare basal and doxorubicin-induced antioxidant enzyme activities in brain, heart, kidney and liver tissues of Fisher 344 rats of different ages to determine whether differences in these enzymes can account for the age-dependent differences observed in doxorubicin-induced toxicity. Three groups of animals were tested, young animals (2-months-old), adult animals (10-months-old) and old animals (18-months-old). The results of these studies show that in general young and adult animals have similar levels of antioxidant enzyme activity while the older animals have less. Only in the young animals is antioxidant enzyme activity significantly increased following doxorubicin treatment suggesting that enzyme induction occurs only in the young group of animals. Lipid peroxidation is shown to have the greatest increase in the old animals following doxorubicin treatment while the young animals have the smallest increase. The results from these studies suggest that there is an increase in doxorubicin-induced oxidative damage with age and that these differences may be due to basal and drug-induced differences in tissue antioxidant enzyme activities.     

Effects of quercetin on antioxidant defense in streptozotocin-induced diabetic rats.

In light of evidence that some complications of diabetes mellitus may be caused or exacerbated by oxidative damage, we investigated the effects of subacute treatment with the antioxidant quercetin on tissue antioxidant defense systems in streptozotocin-induced diabetic Sprague-Dawley rats (30 days after streptozotocin induction). Quercetin, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one, was administered at a dose of 10mg/kg/day, ip for 14 days, after which liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione content, and activities of the free-radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Treatment of normal rats with quercetin increased serum AST and increased hepatic concentration of oxidized glutathione. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Quercetin treatment of diabetic rats reversed only the diabetic effects on brain oxidized glutathione concentration and on hepatic glutathione peroxidase activity. By contrast, a 20% increase in hepatic lipid peroxidation, a 40% decline in hepatic glutathione concentration, an increase in renal (23%) and cardiac (40%) glutathione peroxidase activities, and a 65% increase in cardiac catalase activity reflect intensified diabetic effects after treatment with quercetin. These results call into question the ability of therapy with the antioxidant quercetin to reverse diabetic oxidative stress in an overall sense.     

Cold-stress-induced modulation of antioxidant defence: role of stressed conditions in tissue injury followed by protein oxidation and lipid peroxidation

The aim of this study was to determine the effects of cold stress on antioxidant enzyme activities and examine protein oxidation and lipid peroxidation in various tissues (brain, liver, kidney, heart and stomach). Twenty male Wistar rats (3 months old) weighing 220 ± 20 g were used. The rats were randomly divided into two groups of ten: the control group and the cold stress group. Cold stress was applied to the animals by maintaining them in a cold room (5 °C) for 15 min/day for 15 days. Blood samples were taken for measuring plasma corticosterone levels. Tissues were obtained from each rat for measuring the antioxidant enzyme activities, protein oxidation and lipid peroxidation. Corticosterone levels were increased in the cold stress group. Copper, zinc superoxide dismutase activities were increased in the brains, livers and kidneys, whereas they decreased in the hearts and stomachs of rats in the cold stress group. Catalase activities were increased in the brains, livers, kidneys and hearts, whereas they decreased in the stomachs of rats in the cold stress group. Selenium-dependent glutathione peroxidase activities were increased in the brain, liver, heart and stomach. Reduced glutathione levels were decreased, while levels of protein carbonyl, conjugated diene and thiobarbituric-acid-reactive substances were increased in all tissues of the cold stress group. These results lead us to conclude that cold stress can disrupt the balance in an oxidant/antioxidant system and cause oxidative damage to several tissues by altering the enzymatic and non-enzymatic antioxidant status, protein oxidation and lipid peroxidation.     

Effects of isoeugenol on oxidative stress pathways in normal and streptozotocin-induced diabetic rats.

Because some complications of diabetes mellitus may result from oxidative damage, we investigated the effects of subacute treatment (10mg/kg/day, intraperitoneal [ip], for 14 days) with the antioxidant isoeugenol on the oxidant defense system in normal and 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione content, and activities of the free radical-detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Treatment with isoeugenol reversed diabetic effects on hepatic glutathione peroxidase activity and on oxidized glutathione concentration in brain. Treatment with the lipophilic compound isoeugenol also decreased lipid peroxidation in both liver and heart of normal animals and decreased hepatic oxidized glutathione content in both normal and diabetic rats. Some effects of isoeugenol treatment, such as decreased activity of hepatic superoxide dismutase and glutathione reductase in diabetic rats, were unrelated to the oxidative effects of diabetes. In heart of diabetic animals, isoeugenol treatment resulted in an exacerbation of already elevated activities of catalase. These results indicate that isoeugenol therapy may not reverse diabetic oxidative stress in an overall sense.     

Hyperoxia results in transient oxidative stress and an adaptive response by antioxidant enzymes in goldfish tissues

The effects of hyperoxia on the status of antioxidant defenses and markers of oxidative damage were evaluated in goldfish tissues. The levels of lipid peroxides, thiobarbituric acid reactive substances, carbonyl proteins and the activities of some antioxidant enzymes were measured in brain, liver, kidney and skeletal muscle of goldfish, Carassius auratus L., over a time course of 3-12 h of hyperoxia exposure followed by 12 or 36 h of normoxic recovery. Exposure to high oxygen resulted in an accumulation of protein carbonyls in tissues throughout hyperoxia and recovery whereas lipid peroxides and thiobarbituric acid reactive substances accumulated transiently under short-term hyperoxia stress (3-6 h) but were then strongly reduced. This suggests that hyperoxia stimulated an enhancement of defenses against lipid peroxidation or mechanisms for enhancing the catabolism of peroxidation products. The activities of principal antioxidant enzymes, superoxide dismutase and catalase, were not altered under hyperoxia but catalase increased during normoxic recovery; activities may rise in anticipation of further hyperoxic excursions. In most tissues, the activities of glutathione-utilizing enzymes (glutathione peroxidase, glutathione-S-transferase, glutathione reductase) as well as glucose-6-phosphate dehydrogenase, were not affected under hyperoxia but increased sharply during normoxic recovery. Correlations between some enzyme activities and oxidative stress markers were found, for example, an inverse correlation was seen between levels of thiobarbituric acid reactive substances and glutathione-S-transferase activity in liver and catalase and glucose-6-phosphate dehydrogenase in kidney. The results suggest that liver glutathione-S-transferase plays an important role in detoxifying end products of lipid peroxidation accumulated under hyperoxia stress.     

Changes in antioxidant enzyme activities, fatty acid composition and lipid peroxidation in Daphnia magna during the aging process

Age-related changes in the balance between endogenous pro-oxidative and antioxidative processes in the freshwater cladoceran Daphnia magna (Crustacea) were assessed. The activities of key antioxidant enzymes including catalase, superoxide dismutase and glutathione peroxidase and levels of lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS) were determined in eight age classes, covering juvenile, young and senescent adults. Age-related changes in fatty acid composition were also measured to examine the contribution of polyunsaturated fatty acids (PUFA) in the peroxidation status of animals. Biochemical responses depicted in this study demonstrated that age-related decline in survival was accompanied by increasing oxidative stress and oxidative damage. Enhanced oxidative stress in aging D. magna was suggested by the significant increase in the formation of lipid peroxides, and a concomitant reduction of unsaturated fatty acids of 20 or more carbon atoms. Because aging was accompanied by selective loss of key antioxidant enzymes and small changes in the amount of PUFA, the breakdown of antioxidant defences might have directly contributed to oxidative stress, membrane lipid peroxide and a decline of survival. Indeed, the results reported here, indicate that age-related increases of lipid peroxides were at least partially due to the functional imbalance of enzymatic antioxidant defences.     

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.     

Effects of subacute treatment of ethylene glycol on serum marker enzymes and erythrocyte and tissue antioxidant defense systems and lipid peroxidation in rats

The present study was aimed to investigate the effects of ethylene glycol (EG) on serum marker enzymes, antioxidant defense systems and lipid peroxidation concentration (malondialdehyde=MDA) in various tissues of rats exposed to ethylene glycol. EG (1.25% or 2.5%) in drinking water was administered orally to rats (Sprague-Dawley albino) ad libitum for 21 days continuously. EG treatments caused different effects on the serum marker enzymes, antioxidant defense system and MDA content in various tissues of the treatment groups as compared with the controls. EG also caused a significant increase in the serum marker enzyme activities with 2.5% dosage whereas, no changes were not observed with 1.25% dosage of EG treatment. Lipid peroxidation significantly increased in all the tissues except for in the heart and stomach of rats treated with both dosages of EG. Also, the antioxidative systems were also seriously affected by EG. For example, SOD significantly decreased in the liver treated with both dosages whereas, SOD activity in the erythrocytes, kidney, heart and stomach were significantly increased and not changed in the brain with two dosages of EG. Also, while CAT activity significantly decreased in the erythrocytes, liver and kidney, the activity in the stomach significantly increased, but did not change in the brain and heart with two doses of EG. GR activity significantly decreased in the erythrocytes treated with both dosages of EG whereas GR was not affected in other tissues by EG treatment. GST activity significantly elevated in the heart and brain but did not change in the other tissues of rats treated with both dosages of EG. Meanwhile, GSH depletion in the erythrocytes of rats treated with 2.5% dosage of EG was found to be significant whereas, the level of GSH in the brain was significantly increased treated with both the dosages of EG. The observations presented led us to conclude that the administration of subacute EG promotes lipid peroxidatin content, elevates tissue damage serum marker enzymes and changes in the antioxidative systems in rats. These data, along with the determined changes suggest that EG produced substantial systemic organ toxicity in the erythrocyte, liver, brain, heart kidney and stomach during the period of a 21-day subacute exposure.     

Effect of DL-alpha-lipoic acid on mitochondrial enzymes in aged rats.

Mitochondrial dysfunction appears to contribute to some of the loss of function accompanying ageing. Mitochondria from aged tissue use oxygen inefficiently impairing ATP synthesis and results in increased oxidant production. A high flux of oxidants not only damages mitochondria, but other important cell biomolecules as well. In the present investigation, the levels of lipid peroxidation, oxidized glutathione, non-enzymatic antioxidants and the activities of mitochondrial enzymes were measured in liver and kidney mitochondria of young and aged rats before and after lipoic acid supplementation. In both liver and kidney increase in the levels of mitochondrial lipid peroxidation and oxidized glutathione and decrease in the levels of antioxidants and the activities of mitochondrial enzymes were observed in aged rats. DL-alpha-lipoic acid supplemented aged rats showed a decrease in the levels of lipid peroxidation and oxidized glutathione and increase in the levels of reduced glutathione, vitamins C and E and the activities of mitochondrial enzymes like isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, NADH-dehydrogenase and cytochrome-c-oxidase. Thus, lipoic acid reverses the age-associated decline in endogenous low molecular weight antioxidants and mitochondrial enzymes and, therefore, may lower the increased risk of oxidative damage that occurs during ageing. From our results it can be concluded that lipoic acid supplementation enhances the activities of mitochondrial enzymes and antioxidant status and thereby protects mitochondria from ageing.     

L-malate reverses oxidative stress and antioxidative defenses in liver and heart of aged rats

The intracellular levels of antioxidant and free radical scavenging enzymes are gradually altered during the aging process. An age-dependent increase of oxidative stress occurring throughout the lifetime is hypothesized to be the major cause of aging. The current study examined the effects of L-malate on oxidative stress and antioxidative defenses in the liver and heart of aged rats. Sprague-Dawley male rats were randomly divided into four groups, each group consisting of 6 animals. Group Ia and Group IIa were young and aged control rats. Group Ib and Group IIb were young and aged rats treated with L-malate (210 mg/kg body weight per day). L-malate was orally administrated via intragastric canula for 30 days, then the rats were sacrificed and the liver and heart were removed to determine the oxidant production, lipid peroxidation and antioxidative defenses of young and aged rats. Dietary L-malate reduced the accumulation of reactive oxygen species (ROS) and significantly decreased the level of lipid peroxidation in the liver and heart of the aged rats. Accordingly, L-malate was found to enhance the antioxidative defense system with an increased activity of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) and increased glutathione (GSH) levels in the liver of aged rats, a phenomenon not observed in the heart of aged rats. Our data indicate that oxidative stress was reversed and the antioxidative defense system was strengthened by dietary supplementation with L-malate.     

Effects of piperine on antioxidant pathways in tissues from normal and streptozotocin-induced diabetic rats

Using diabetes mellitus as a model of oxidative damage, this study investigated whether subacute treatment (10 mg/kg/day, intraperitoneally for 14 days) with the compound piperine would protect against diabetes-induced oxidative stress in 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione (GSH and GSSG, respectively) content, and activities of the free-radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Piperine treatment of normal rats enhanced hepatic GSSG concentration by 100% and decreased renal GSH concentration by 35% and renal glutathione reductase activity by 25% when compared to normal controls. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Treatment with piperine reversed the diabetic effects on GSSG concentration in brain, on renal glutathione peroxidase and superoxide dismutase activities, and on cardiac glutathione reductase activity and lipid peroxidation. Piperine treatment did not reverse the effects of diabetes on hepatic GSH concentrations, lipid peroxidation, or glutathione peroxidase or catalase activities; on renal superoxide dismutase activity; or on cardiac glutathione peroxidase or catalase activities. These data indicate that subacute treatment with piperine for 14 days is only partially effective as an antioxidant therapy in diabetes.     

Oxidative damage increases with age in a canine model of human brain aging

We assayed levels of lipid peroxidation, protein carbonyl formation, glutamine synthetase (GS) activity and both oxidized and reduced glutathione to study the link between oxidative damage, aging and beta-amyloid (Abeta) in the canine brain. The aged canine brain, a model of human brain aging, naturally develops extensive diffuse deposits of human-type Abeta. Abeta was measured in immunostained prefrontal cortex from 19 beagle dogs (4-15 years). Increased malondialdehyde (MDA), which indicates increased lipid peroxidation, was observed in the prefrontal cortex and serum but not in cerebrospinal fluid (CSF). Oxidative damage to proteins (carbonyl formation) also increased in brain. An age-dependent decline in GS activity, an enzyme vulnerable to oxidative damage, and in the level of glutathione (GSH) was observed in the prefrontal cortex. MDA level in serum correlated with MDA accumulation in the prefrontal cortex. Although 11/19 animals exhibited Abeta, the extent of deposition did not correlate with any of the oxidative damage measures, suggesting that each form of neuropathology accumulates in parallel with age. This evidence of widespread oxidative damage and Abeta deposition is further justification for using the canine model for studying human brain aging and neurodegenerative diseases.     

Effects of cod liver oil on tissue antioxidant pathways in normal and streptozotocin-diabetic rats

Lipid disorders and increased oxidative stress may exacerbate some complications of diabetes mellitus. Previous studies have implicated the beneficial effects of some antioxidants, omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the protection of cells from the destructive effect of increased lipids and lipid peroxidation products. This study, therefore, was designed to investigate the effects of cod liver oil (CLO, Lysi Ltd. Island), which comprises mainly vitamin A, PUFAs, EPA and DHA. Effects were monitored on plasma lipids, lipid peroxidation products (MDA) and the activities of antioxidant enzymes, glutathione peroxidase (GSHPx) and catalase in heart, liver, kidney and lung of non-diabetic control and streptozotocin (STZ)-induced-diabetic rats. Two days after STZ-injection (55 mg kg(-1) i.p.), non-diabetic control and diabetic rats were divided randomly into two groups as untreated or treated with CLO (0.5 ml kg(-1) rat per day) for 12 weeks. Plasma glucose, triacylglycerol and cholesterol concentrations were significantly elevated in 12-week untreated-diabetic animals; CLO treatment almost completely prevented these abnormalities in triacylglycerol and cholesterol, but hyperglycaemia was partially controlled. CLO also provided better weight gain in diabetic animals. In untreated diabetic rats, MDA markedly increased in aorta, heart and liver but was not significantly changed in kidney and lung. This was accompanied by a significant increase in both GSHPx and catalase enzyme activities in aorta, heart, and liver of diabetic rats. In kidney and lung, diabetes resulted in reduced catalase while GSHPx was significantly activated. In aorta, heart, and liver, diabetes-induced changes in MDA were entirely prevented by CLO treatment. In the tissues of CLO-treated diabetic animals, GSHPx activity paralleled those of control animals. CLO treatment also caused significant improvements in catalase activities in every tissue of diabetic rats, but failed to affect MDA and antioxidant activity in control animals. The current study suggests that the treatment of diabetic rats with CLO provides better control of glucose and lipid metabolism, allows recovery of normal growth rate, prevents oxidative/peroxidative stress and ameliorates endogenous antioxidant enzyme activities in various tissues. Because CLO contains a plethora of beneficial compounds together, its use for the management of diabetes-induced complications may provide important advantages.     

Age-related changes in antioxidant enzymes and lipid peroxidation in brains of control and transgenic mice overexpressing copper-zinc superoxide dismutase.

The aim of our study was first to obtain a comprehensive profile of the brain antioxidant defense potential and peroxidative damage during aging. We investigated copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), seleno-dependent glutathione peroxidase (GSH-PX), glutathione reductase (GSSG-R) activities, endogenous and in vitro stimulated lipid peroxidation in 40 brains of control mice divided into 3 age groups: 2 months (young), 12 months (middle-aged) and 28 months (old). We found a positive correlation between age and activities of CuZnSOD (r = 0.47; P < 0.01) and GSH-PX (r = 0.72; P < 0.0001). CuZnSOD and GSH-PX activities are independently regulated during brain aging since temporal changes of these two enzymes do not correlate. No modification in MnSOD activity and basal lipid peroxidation was observed as a function of age. Nevertheless, stimulated lipid peroxidation was significantly higher at 12 months (6.53 +/- 0.71 mumole MDA/g tissue) than at 2 months (5.69 +/- 0.90) and significantly lower at 28 months (5.13 +/- 0.33) than at 12 months. Second, we used genetic manipulations to construct transgenic mice that specifically overexpress CuZnSOD to understand the role of CuZnSOD in neuronal aging. The human CuZnSOD transgene expression was stable during aging. The increased CuZnSOD activity in the brain (1.9-fold) of transgenic mice resulted in an enhanced rate of basal lipid peroxidation and in increased MnSOD activity in the 3 age groups. Other antioxidant enzymes did not exhibit modifications indicating the independence of the regulation between CuZnSOD and glutathione-related enzymes probably due to their different cellular localization in the brain.     

Relationship between antioxidant potential and oxidative damage to lipids, proteins and DNA in aged rats

Oxidative stress has been implicated to play a major role in aging and age-related diseases. In the present study, we investigated the effects of aging on the total antioxidant capacity, uric acid, lipid peroxidation, total sulfhydryl group content and damage to DNA in adult (6 months), old (15 months) and senescent (26 months) male Wistar rats. The antioxidant capacity, determined by phycoerythrin-based TRAP method (total peroxyl radical-trapping potential) was significantly decreased in the plasma and myocardium of old and senescent rats, whereas plasma level of uric acid was elevated in 26-month-old rats. Age-related decline in plasma and heart antioxidant capacity was accompanied by a significant loss in total sulfhydryl group content, increased lipid peroxidation and higher DNA damage in lymphocytes. Correlations between TRAP and oxidative damage to lipids, proteins and DNA suggest that the decline in antioxidant status may play an important role in age-related accumulation of cell damage caused by reactive oxygen species.     

Preventive effect of safranal against oxidative damage in aged male rat brain

An imbalance between production of reactive oxygen species (ROS) and its elimination by antioxidant defense system in the body has been implicated for causes of aging and neurodegenerative diseases. This study was design to assess the changes in activities of antioxidant enzymes (superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase), lipid peroxidation and reduced glutathione (GSH) levels in the brain of 2, 10 and 20 month old rats, and to determine the effect of safranal on the status of selected oxidative stress indices in the 10 and 20 month old rats. The aged rats (10 and 20 months) were given intraperitoneal injections of safranal (0.5 mg/kg day) daily for one month. The results of this study demonstrated that aging caused significant increase in the level of lipid peroxidation as well decrease in the GSH level and activities of SOD and GST in the brain of aging rats. The results of this study showed that safranal ameliorated the increased lipid peroxidation level as well as decreased GSH content of the brain of 10 and 20 month old rats. In addition, safranal treatment to the 20 month old rats, which restored the SOD and GST activities. In conclusion, safranal can be effective to protect susceptible aged brain from oxidative damage by increasing antioxidant defenses.     

Lipid peroxidation and activity of antioxidant enzymes in diabetic rats

We hypothesized that oxygen free radicals (OFRs) may be involved in pathogenesis of diabetic complications. We therefore investigated the levels of lipid peroxidation by measuring thiobarbituric acid reactive substances (TBARS) and activity of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] in tissues and blood of streptozotocin (STZ)-induced diabetic rats. The animals were divided into two groups: control and diabetic. After 10 weeks (wks) of diabetes the animals were sacrificed and liver, heart, pancreas, kidney and blood were collected for measurement of various biochemical parameters. Diabetes was associated with a significant increase in TBARS in pancreas, heart and blood. The activity of CAT increased in liver, heart and blood but decreased in kidney. GSH-Px activity increased in pancreas and kidney while SOD activity increased in liver, heart and pancreas. Our findings suggest that oxidative stress occurs in diabetic state and that oxidative damage to tissues may be a contributory factor in complications associated with diabetes.