Lipid peroxidation and scavenging enzyme levels in the liver of streptozotocin-induced diabetic rats

In this study, alterations in the liver antioxidant enzymes status and lipid peroxidation in short-term (8-weeks) and long-term (24-weeks) diabetic rats were examined. Glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) levels were significantly increased, but superoxide dismutase (SOD) activity was significantly reduced in 8-weeks diabetic rats, compared to control. Catalase (CAT) activity, however, was found unchanged. In 24-weeks diabetic rats, while GSH-Px activity was unchanged, but SOD and CAT activities and MDA levels were significantly increased, compared to control. These results suggest that diabetes-induced alterations in tissue antioxidant system may reflect a generalized increase in tissue oxidative stress. It can be concluded that lipid peroxidation and antioxidant enzyme levels are elevated in diabetic condition. Hence, diabetes mellitus, if left untreated, may increase degenerative processes due to accumulation of oxidative free radicals.     

Effects of simvastatin treatment on oxidant/antioxidant state and ultrastructure of diabetic rat myocardium

In the present study we investigated the effects of simvastatin treatment on lipid metabolism and peroxidation, antioxidant enzyme activities and ultrastructure of the diabetic rat myocardium. Diabetes was induced by single injection of streptozotocin (45 mg/kg i.p.). Eight weeks after induction of diabetes, a subgroup of control and of diabetic rats was treated with simvastatin for 4 weeks (10 mg/kg/day, orally). Blood glucose, plasma cholesterol and triacylglycerol, as well as levels of cardiac thiobarbituric acid reactive substances (TBARS) were significantly increased in diabetic rats. The activities of antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GSHPx), were also elevated in the diabetic myocardium. Treatment with simvastatin markedly reduced serum triacylglycerol and cholesterol, and partially controlled hyperglycemia in diabetic animals. The increased activation of antioxidant enzymes and the excess of lipid peroxidation measured by TBARS were completely reversed by simvastatin treatment. Diabetic rats displayed ultrastructural ischemia-like alterations of cardiomyocytes and capillaries, which support oxidative stress-induced tissue remodelling. In the diabetic myocardium simvastatin treatment partly attenuated angiopathic and atherogenic processes, detected by electron microscopy. These results suggest that simvastatin, known as a lipid-lowering drug, may positively affect diabetes induced cardiovascular complications via reducing risks of atherosclerotic pathological processes, such as imbalance between oxidant and antioxidant state.     

Changes in the activity of enzymes,participating in glycogen metabolism of alloxan diabetic rats

Summary Alloxan diabetes induced in white rats by intraperitoneal injection of Aloxan-monohydrate (15 mg/100 g body weight) was used to study changes in the glycogen phosphorylase a and b, phosphoprotein phosphatases and hexokinase activities under insulin deficiency conditions. Among the enzymes studied, an increase in muscle phosphorylase a activity as well as the a/b ratio have been obtained. In diabetic muscle phosphoprotein phosphatases and hexokinase activities were diminished.AMP increased the liver glycogen phosphorylase activity twice in diabetic rats whereas in normal animals the enzyme was less sensitive to this effector. The changes in liver hexokinase activity at diabetes were not connected and correlated with the altered phosphorylase and protein phosphatase activities.The logical chain of probable molecular events taking place in muscle glycogen metabolism under the conditions of insulin deficiency is offered.     

Intestinal damage induced by zinc deficiency is associated with enhanced CuZn superoxide dismutase activity in rats: effect of dexamethasone or thyroxine treatment.

Zinc has a wide spectrum of biological activities and its deficiency has been related to various tissue dysfunctions and alterations of normal cell metabolism. Zinc also plays an important role in the antioxidant cellular defenses being a structural element of the non-mitochondrial form of the enzyme superoxide dismutase (CuZnSOD). We have already reported that Zn deficiency induces severe alterations in the rat intestine, that are reverted by treatment with dexamethasone (Dex) or thyroxine (T4). Here we report a paradoxical increase of CuZnSOD activity in rat intestine after 20 and 40 days of zinc deficiency. The increase of CuZnSOD activity is not due to an upregulation of gene expression because both Northern and Western blot analysis indicate that CuZnSOD mRNA and protein levels are not affected by zinc deficiency. A significant increase of lipid peroxidation was also observed in duodenum and jejunum associated with zinc deficiency. Treatment with either Dex or T4 to zinc-deficient rats protects against intestinal oxidative damage and results in SOD activity similar to control rats. Because glutathione peroxidase and catalase activities decreased in zinc deficiency, we speculate that the increase in SOD activity may be associated with an accumulation of hydrogen peroxide that may activate inflammatory molecules, further worsening tissue damage.     

Effects of UV-B radiation on antioxidant parameters of iron-deficient barley plants

Iron deficiency is a stress frequently experienced by plants, owing to the low solubility of Fe(III) salts in neutral or alcaline soils. Iron is an essential plant nutrient as it is involved in fundamental metabolic processes. Furthermore, it is a constituent of important antioxidant enzymes, which are involved in maintaining the balance of cell redox state. UV-B radiation is an environmental problem which can alter the redox state of plants through the increased production of reactive oxygen species. In order to investigate if iron deficiency influences the antioxidant response of plants to UV-B radiation, barley seedlings, Hordeum vulgare L. cv. Express, were exposed to UV-B radiation while growing in nutrient solutions with or without iron. After eight days of growth, plants were harvested and analysed. Results show that, during the 8 days of the experimental period, in neither of the two nutritional conditions considered does UV-B exposure reduce shoot weight or induce evident alterations of thylakoid membranes in respect to controls. However, different responses to UV-B radiation between iron-deficient and iron-sufficient plants were observed at the level of parameters related to oxidative stress. In fact, in iron-sufficient plants the contents of photosynthetic pigments and ascorbate, and the enzyme activities of ascorbate peroxidase (EC 1.11.1.11) and catalase (EC 1.11.1.6) were not affected by UV-B radiation. Conversely, in iron-deficient plants the contents of ascorbate and zeaxanthin and the activity of ascorbate peroxidase increased under UV-B exposure, whereas catalase activity decreased. Furthermore, UV-B radiation induced an increase of hydrogen peroxide content which was higher in iron-deprived plants than in iron-sufficient ones. This may indicate that plants growing in an environment enriched in UV-B radiation may develop a high level of oxidative stress when iron supply is limited.     

Tissue antioxidant status in streptozotocin-induced diabetes in rats

Interactions between manganese (Mn) deficiency and streptozotocin (STZ)-diabetes with respect to tissue antioxidant status were investigated in male, Sprague-Dawley rats. All rats were fed either a Mn-deficient (1 ppm) or a Mn-sufficient (45 ppm) diet for 8 wk. Diabetes was then induced by tail-vein injection of STZ (60 mg/kg body weight), after which the rats were kept for an additional 4 or 8 wk. The control groups comprised rats not injected with STZ and fed either Mn-deficient or Mn-sufficient diets for a total of 12 wk. The Mn-deficient diet decreased the activities of manganese superoxide dismutase (MnSOD) in kidney and heart, and of copperzinc superoxide dismutase (CuZnSOD) in kidney, in the non-diabetic animals. In the diabetic rats, the Mn-deficient diet induced more pronounced decreases in activities of these same enzymes, and also increased liver MnSOD activity. Plasma and hepatic vitamin E levels increased progressively with the duration of diabetes, independent of dietary Mn intake. Lipid peroxidation, as measured by H₂O₂-induced production of thiobarbituric acid reactive substances in erythrocytes, also increased, concomitant with decreased liver and kidney glutathione (GSH) levels. These findings demonstrate for the first time an interactive effective between Mn deficiency and STZ-diabetes, resulting in amplification of tissue antioxidant changes seen with either Mn deficiency or STZ-diabetes alone. This effect of Mn deprivation in experimental diabetes suggests a physiological role for Mn as an antioxidant nutrient.     

Selenium treatment protects diabetes-induced biochemical and ultrastructural alterations in liver tissue

We have shown that a single dose of streptozotocin (STZ) (50 mg/kg body weight) injected into rats caused significant changes in some antioxidant enzyme activities, such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase activities, and acid-soluble sulfhydryl levels of the liver tissue with respect to the control rats. Furthermore, these alterations in the activities of the antioxidant enzymes were accompanied by significant changes in the ultrastructure of the liver tissue; mainly intercellular biliary canaliculi were distended and contained stagnant bile, swollen mitochondria in hepatocytes and disoriented and disintegrating cristae, dilatation of the rough endoplasmic reticulum (rER) with detachment of ribosomes, and dissociation of polysomes. Both diabetic and normal rats were treated with sodium selenite (5 micromol/kg/d, intra peritoneally) for 4 wk following 1 wk of diabetes induction. This treatment of diabetic rats improved significantly diabetes-induced alterations in liver antioxidant enzymes. Moreover, treating of diabetic rats with sodium selenite prevented primarily the variation in staining quality of hepatocytes nuclei, increased density and eosinophilia of the cytoplasm, focal sinusoidal dilatation and congestion, and increased numbers of mitochondria with different size and shape. In summary, treatment of diabetic rats with sodium selenite has beneficial effects on both antioxidant system and the ultrastructure of the liver tissue. These findings suggest that diabetes-induced oxidative stress can be responsible for the development of diabetic complications and antioxidant treatment can protect the target organs against diabetes.     

Antioxidant status in the liver of hypertensive and metallothionein-deficient mice

Because oxidative stress is involved in arterial hypertension, impairment of hepatic antioxidant defences could develop in the course of this disease. Metallothionein (MT), an antioxidant protein, is present in high rates in the liver. The aim of this study was to investigate the effect of a mineralocorticoid-salt treatment on blood pressure, hepatic antioxidant enzyme activities, and cardiac MT levels in transgenic MT null mice compared with control mice to further clarify the role of MT during the experimental development of arterial hypertension. Control and transgenic MT -/- mice were submitted to an 8-week mineralocorticoid-salt treatment. Hepatic glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase activities and cardiac MT and mineral levels were measured. Mineralocorticoid-salt treatment induced an increase in blood pressure in both transgenic MT -/- and control mice that was associated with an impairment of liver antioxidant status. MT deficiency was associated with modifications of hepatic antioxidant enzyme activities and with a decrease in cardiac iron levels. Adaptive processes of antioxidant systems may explain the absence of an effect of metallothionein deficiency on the development of mineralocorticoid-salt hypertension. The interactions that occur between the in vivo antioxidant systems probably produce a complex regulation of the oxidative balance and consequently prevent antioxidant deficiency.     

Selenium Supplementation Modulates Zinc Levels and Antioxidant Values in Blood and Tissues of Diabetic Rats Fed Zinc-Deficient Diet

Diabetes mellitus is associated to a reduction of antioxidant defenses that leads to oxidative stress and complications in diabetic individuals. The present study was undertaken to investigate the effect of selenium on blood biochemical parameters, antioxidant enzyme activities, and tissue zinc levels in alloxan-induced diabetic rats fed a zinc-deficient diet. The rats were divided into two groups; the first group was fed a zinc-sufficient diet, while the second group was fed a zinc-deficient diet. Half of each group was treated orally with 0.5 mg/kg sodium selenite. Tissue and blood samples were taken from all animals after 28 days of treatment. At the end of the experiment, the body weight gain and food intake of the zinc-deficient diabetic animals were lower than that of zinc-adequate diabetic animals. Inadequate dietary zinc intake increased glucose, lipids, triglycerides, urea, and liver lipid peroxidation levels. In contrast, serum protein, reduced glutathione, plasma zinc and tissue levels were decreased. A zinc-deficient diet led also to an increase in serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and liver glutathione-S-transferase and to a decrease in serum alkaline phosphatase activity and glutathione peroxidase. Selenium treatment ameliorated all the values approximately to their normal levels. In conclusion, selenium supplementation presumably acting as an antioxidant led to an improvement of insulin activity, significantly reducing the severity of zinc deficiency in diabetes.     

Beneficial effects of selenium on some enzymes of diabetic rat heart

It is known that selenium compounds can restore some metabolic parameters in experimental diabetes. However, as there are no, clear data about their effects on the altered antioxidant defense system of the diabetic heart, we aimed to investigate whether these beneficial effects extend to the alterations of some enzyme activities, which play important roles in antioxidant defense system. Diabetes was induced by streptozotocin (50 mg/kg body weight) and rats were then treated with sodium selenite (5 μmol/kg/d) for 4 wk. Sodium selenite treatment of the diabetic rats significantly restored the altered activities of glutathione- S-transferase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase, which are involved in the glutathione metabolism of the heart, but slightly but significantly decreased the high blood glucose level. In summary, the present study suggests that the beneficial effects of sodium selenite treatment appears to be the result of the restoration altered activities of the antioxidant enzymes in diabetic heart tissue.     

Riboflavin nutritional status and flavoprotein enzymes in streptozotocin-diabetic rats

Riboflavin nutritional status was assessed on the basis of activity coefficients of glutathione reductase in erythrocyte hemolysates of normal and streptozotocin-diabetic rats. Activity coefficient values higher than 1.3 were regarded as evidence of riboflavin deficiency. All diabetic animals were found to be riboflavin-deficient, with activity coefficient values of 1.47–2.11. Treatment of diabetic rats with either insulin or riboflavin returned their activity coefficients to normal. Rats fed a restricted diet had normal activity coefficient values. The erythrocyte glutathione reductase activity was significantly lower in diabetic rats, and the augmentation of enzyme activity in the presence of flavin-adenine dinucleotide (FAD) was 72% compared to 16% in normal rats. Hepatic activities of glutathione reductase and succinate dehydrogenase, both FAD-containing enzymes, were significantly lower in diabetic than in normal rats. Like activity coefficient values, all enzyme activities were normalized after insulin or riboflavin treatments. These data suggest that insulin and riboflavin enhance the synthesis of erythrocyte and hepatic FAD. The results of the present study suggest that experimental diabetes causes riboflavin deficiency, which in turn decreases erythrocyte and hepatic flavoprotein enzyme activities. These changes can be corrected for by either insulin or riboflavin. The pathogenesis of riboflavin deficiency in diabetes mellitus is not clearly understood. The data of the present study provide evidence in addition to the previous findings of an increased prevalence of riboflavin deficiency in genetically diabetic KK mice.     

Antioxidant enzyme alterations in experimental and clinical diabetes

Previous studies from our laboratory have demonstrated the presence of complex alterations in the activities of antioxidant enzymes in various tissues of rats with streptozotocin (STZ)-induced diabetes. In the present investigation, it is shown that rats made diabetic with alloxan (ALX), an agent differing from STZ both chemically and in its mechanism of diabetogenesis, show virtually identical tissue antioxidant enzyme changes which, as is the case with STZ, are preventable by insulin treatment. The finding that the patterns of antioxidant enzyme alterations in chemically-induced diabetes are independent of the diabetogenic agent used and the presence of similar abnormalities in tissues of spontaneously diabetic (BB) Wistar rats (particularly when diabetic control is less than optimal) suggest that the changes observed are a characteristic feature of the uncontrolled diabetic state and that these may be responsible for (or predispose to) the development of secondary complications in clinical diabetes. Comparative studies involving red cells of diabetic rats and human diabetics revealed a number of common changes, namely an increase in glutathione reductase activity, a decreased susceptibility to oxidative glutathione depletion (which was related to the presence of hyperglycemia) and an increased production of malondialdehyde (an indirect index of lipid peroxidation) in response to in vitro challenge with hydrogen peroxide. In the diabetic patients, the extent of this increase in susceptibility of red cell lipids to oxidation paralleled the severity of diabetic complications. Our results suggest that increased (or uncontrolled) oxidative activity may play an important role in the pathogenesis of complications associated with the chronic diabetic state.This work was supported by grants from the British Columbia Health Care Research Foundation and the Canadian Diabetes Association.     

Liver Lipid Composition and Antioxidant Enzyme Activities of Spontaneously Hypertensive Rats After Ingestion of Dietary Fats (Fish, Olive and High-Oleic Sunflower Oils)

Hypertension is associated with greater than normal lipoperoxidation and an imbalance in antioxidant status, suggesting that oxidative stress is important in the pathogenesis of this disease. Although many studies have examined the effect of antioxidants in the diet on hypertensión and other disorders, less attention has been given to the evaluation of the role of specific dietary lipids in modulating endogenous antioxidant enzyme status. Previously, we have described that liver antioxidant enzyme activities may be modulated by consumption of different oils in normotensive rats. The purpose of the present study was to examine the effects of feeding different lipidic diets (olive oil, OO, high-oleic-acid sunflower oil, HOSO, and fish oil, FO) on liver antioxidant enzyme activities of spontaneously hypertensive rats (SHR). Plasma and liver lipid composition was also studied. Total triacylglycerol concentration increases in plasma and liver of animals fed on the HOSO and OO diets and decreases in those fed on the FO diet, relative to rats fed the control diet. The animals fed on the oil-enriched diet show similar hepatic cholesterol and phospholipid contents, which are higher than the control group. Consumption of the FO diet results in a decrease in the total cholesterol and phospholipid concentration in plasma, compared with the high-oleic-acid diets. In liver, the FO group show higher levels of polyunsaturated fatty acids (PUFA) of the (n-3) series, in relation to the animals fed on the diets enriched in oleic acid. Livers of FO-fed rats, compared with those of OO- and HOSO-fed rats showed: (i) significantly higher activities of catalase, glutathione peroxidase and Cu/Zn superoxide dismutase; (ii) no differences in the NADPH-cytochrome c reductase activity. The HOSO diet had a similar effect on liver antioxidant enzyme activities as the OO diet. In conclusion, it appears that changes in the liver fatty acid composition due mainly to n-3 lipids may enhance the efficiency of the antioxidant defence system and may yield a benefit in the hypertension status. The two monounsaturated fatty acids oils studied (OO and HOSO), with the same high content of oleic acid, but different content of natural antioxidants, had similar effects on the antioxidant enzyme activities studied.     

Atrophy of the thymus in rats rendered diabetic by streptozotocin

The thymus atrophied rapidly in rats rendered diabetic by a single injection of streptozotocin. The weight of the gland was reduced to one-fifth of its original weight within three weeks. Histologically there was a great loss of cortical thymocytes and a marked increase in mast cells lying in the thickened fibrous tissue. These findings may have a bearing on the state of immune deficiency observed in animals with diabetes induced by streptozotocin.     

Thiol supplementation in aged animals alters antioxidant enzyme activity after heat stress.

Declines in oxidative and thermal stress tolerance are well documented in aging systems. It is thought that these alterations are due in part to reductions in antioxidant defenses. Although intracellular thiols are major redox buffers, their role in maintaining redox homeostasis is not completely understood, particularly during aging, where the reliance on antioxidant enzymes and proteins may be altered. To determine whether thiol supplementation improved the antioxidant enzyme profile of aged animals after heat stress, young and old Fischer 344 rats were treated with N-acetylcysteine (NAC; 4 mmol/kg ip) 2 h before heat stress. Liver tissue was collected before and 0, 30, and 60 min after heat stress. Aging was associated with a significant decline in tissue cysteine and glutathione (GSH) levels. There was also an age-related decrease in copper-zinc superoxide dismutase activity. Heat stress did not alter liver GSH, glutathione disulfide, or antioxidant enzyme activity. With NAC treatment, old animals took up more cysteine than young animals as reflected in an increase in liver GSH and a corresponding decrease in glutamate cysteine ligase activity. Catalase activity increased after NAC treatment in both age groups. Copper-zinc superoxide dismutase activity did not change with heat stress or drug treatment, whereas manganese superoxide dismutase activity was increased in old animals only. These data indicate that GSH synthesis is substrate limited in old animals. Furthermore, aged animals were characterized by large fluctuations in antioxidant enzyme balance after NAC treatment, suggesting a lack of fine control over these enzymes that may leave aged animals susceptible to subsequent stress.     

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.     

The changes in the antioxidant status of heart during experimental hypomagnesemia in balb/c mice

The present experiment was performed to assess if hypomagnesemia can influence antioxidant status in mice heart. The results could explain possibly a free radical theory of heart damage in magnesium deficiency. We used a rodent model of hypomagnesemia. The magnesium sufficient group received a standard diet whereas a magnesium deficient group received the diet containing a trace amount of magnesium. The activities of the most important antioxidant enzymes – catalase, glutathione peroxidase and superoxide dismutase were assessed in mice heart and liver in a time dependent manner, on the 10th and the 20th day of experiment. The level of magnesium in plasma of animals receiving the magnesium deficient diet dropped twice after the 8th day and four times after the 13th day and then reached a plateau value. The activity of catalase in heart in the magnesium deficient group increased gradually and was significantly (P<0.05) elevated by 27% on the 20th day of experiment whereas the superoxide dismutase activity was significantly decreased by 17% on the 20th day. Glutathione peroxidase activity was insignificantly elevated. The alterations of antioxidant enzyme activities in the heart indicate cardiomyocytes's exposure to oxidative stress, which can be responsible for the cardiac lesions observed during hypomagnesemia.     

Vitamin E and oxidative stress

Oxidative stress can result from or be enhanced by a large variety of conditions, including nutritional imbalance, exposure to chemical and physical agents in the environment, strenuous physical activities, injury, and hereditary disorders. While many enzymes and compounds are involved in protecting cells from the adverse effects of oxidative stress, vitamin E occupies an important and unique position in the overall antioxidant defense. The antioxidant function of vitamin E is closely related to the status of many dietary components. Vitamin E-depleted animals are generally more susceptible to the adverse effects of environmental agents than supplemented animals. Also, vitamin E supplementation is beneficial to certain groups of the population. However, supplementing vitamin E in experimental subjects maintained on a nutritionally adequate diet does not always provide additional protection. Differential metabolic responses in various organs and differences in experimental conditions often contribute in the discrepancies in the literature. The lack of clear evidence for the occurrence of lipid peroxidation or antioxidant function of vitamin E in vivo can be attributed partly to the presence of active pathways for metabolizing hydroperoxides, aldehydes, and other oxidation products. Specific and sensitive techniques for measuring lipid peroxidation products in biological systems are essential for understanding the role of free radical-induced lipid peroxidation in tissue damage and antioxidant function of vitamin E in vivo.     

Superoxide dismutase, catalase and glutathione peroxidase activities in the brain of streptozotocin induced diabetic rats

Brain antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) levels were studied in the brains of early diabetic (72 hr) and long term diabetic (one month) rats. Diabetes was induced by injecting streptozotocin (50 mg/kg, i.p.) in citrate buffer. One group of diabetic rats was treated with insulin (1U/day/animal). The results indicate that early diabetic rats exhibit increased SOD and CAT activities with no alteration in the GPX activity. On the contrary, increased CAT decreased GPX activities with no alteration in the SOD activity, was noted in the long-term Diabetic rats. Insulin treatment reversed these alterations in both the groups. It can be concluded that, in diabetic condition antioxidant enzyme levels are elevated and insulin treatment attenuated these changes. Hence, diabetes mellitus, if left untreated, may initiate degenerative processes and other CNS complications due to accumulation of oxidative 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.