Taurine modulates kallikrein activity and glucose metabolism in insulin resistant rats

Summary. Taurine, a potent antioxidant has been reported to show an antidiabetic effect in streptozotocin-induced diabetes mellitus in which the development of hyperglycemia results from the damage to β cells of pancreas by reactive oxygen species. In addition, taurine also increases the excretion of nitrite and enhances the formation of kinins and would be expected to improve insulin resistance. The effect of taurine on insulin sensitivity was examined in the high fructose-fed rats, an animal model of insulin resistance. Male Wistar rats of body weight 170–190 g were divided into 4 groups: a control group and taurine-supplemented control group, taurine supplemented and unsupplemented fructose-fed group. An intravenous glucose tolerance test (IVGTT) and a steady state plasma glucose level (SSPG) were performed before the sacrifice. The fructose-fed rats displayed hyperglycemia and insulin resistance and they had a greater accumulation of glycogen than did control rats. Hyperglycemia and insulin resistance were significantly lower in the taurine supplemented fructose-fed group than in the unsupplemented fructose-fed group. Urinary kallikrein activity was higher in taurine-treated animals than in the rats fed only fructose. The activity of membrane bound ATPases were significantly lower in fructose-fed rats than in the control rats and were significantly higher in the taurine supplemented group than in the fructose-fed group. Taurine effectively improves glucose metabolism in fructose-fed rats presumably via improved insulin action and glucose tolerance. Received January 5, 2001 Accepted August 21, 2001     

Potential role of kinins in the effects of taurine in high-fructose-fed rats

The present work investigates the involvement of kinins in the effects of taurine in fructose-fed hypertensive rats. The effects of taurine on blood pressure, plasma glucose, insulin, and the insulin sensitivity index were determined. Angiotensin-converting enzyme (ACE) activity and nitrite content in plasma, plasma and tissue kallikrein activity, and taurine content were also investigated. The blood pressure changes in response to the coadministration of inhibitors of the synthesis of nitric oxide (NO), prostaglandins (PGs), or a kinin receptor blocker along with taurine was also evaluated. Fructose-fed rats had higher blood pressure and elevated plasma levels of glucose and insulin. Kallikrein activity, taurine, and nitrite contents were significantly lower in fructose-fed rats as compared with controls. The increases in systolic blood pressure, hyperglycemia, and hyperinsulinemia were controlled by taurine administration in fructose-fed rats. ACE activity was lower, while nitrite and taurine content and kallikrein activity were higher, in taurine-supplemented rats as compared with fructose-fed rats. A significant increase in blood pressure was observed in rats cotreated with the inhibitors Hoe 140 (a kinin receptor blocker), L-NAME (a NO synthase inhibitor), or indomethacin (a PG synthesis inhibitor) with taurine for 1 week as compared with taurine-treated fructose-fed rats. This suggests that the antihypertensive effect of taurine in fructose-fed rats was blocked by the inhibitors. Augmented kallikrein activity and, hence, increased kinin availability may be implicated in the effects of taurine in fructose-fed hypertensive rats.     

Quercitrin a bioflavonoid improves the antioxidant status in streptozotocin: induced diabetic rat tissues

Quercitrin, a bio flavonoid, was investigated for its antioxidant potential in streptozotocin (STZ)-induced diabetic rats. Rats were induced diabetic by a single intraperitoneal injection of streptozotocin (50 mg/kg). The levels of fasting plasma glucose and insulin were estimated. Lipid peroxidative products and antioxidants were estimated in pancreas, liver, and kidney. Histopathological studies were carried out in these tissues. A significant (P < 0.05) increase in the levels of fasting plasma glucose and lipid peroxidative products (thiobarbituric acid reactive substances and lipid hydroperoxides) and a significant (P < 0.05) decrease in plasma insulin, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), and nonenzymic antioxidants (reduced glutathione, vitamin C, and E) in diabetic pancreas, liver, and kidney were observed. Oral administration of quercitrin (30 mg/kg) for a period of 30 days significantly (P < 0.05) decreased fasting plasma glucose, increased insulin levels, and improved the antioxidant status of diabetic rats by decreasing lipid peroxidative products and increasing enzymic and nonenzymic antioxidants. Normal rats treated with quercitrin (30 mg/kg) showed no significant (P < 0.05) effect on any of the parameters studied. Histopathological studies of the pancreas, liver, and kidney showed the protective role of quercitrin. Thus, our study clearly shows that quercitrin has antioxidant effect in STZ-induced experimental diabetes.     

Garlic and vitamin E provides antioxidant defence in tissues of female rats treated with nicotine

Nicotine is known to induce oxidative stress in rat tissues and the antioxidant properties of garlic have been reported. This study was designed to determine if the peroxidative damage caused by nicotine administration can be effectively prevented with garlic juice, and vitamin E, a known antioxidant.Four groups of six rats each were divided into: Group I: (control) received 0.2ml of 0.9% normal saline, group II (received nicotine 0.6mg/kg b.w subcutaneously), group III (received nicotine 0.6mg/kg b.w + garlic juice 100mg/kg b.w orally), and group IV (received nicotine 0.6mg/kg b.w + Vitamin E 100mg/kg b.w orally). All animals were treated for 21 days. The pituitary gland, ovary, uterus, heart, liver and kidney of the animals were harvested, weighed and homogenized. Malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) were then measured.Concentration of MDA was significantly increased in tissues of nicotine treated rats when compared with the control. In group III and IV, MDA levels were significantly reduced when compared with nicotine group. The activities of SOD and GSH significantly decreased in group II (nicotine only) rat tissues, while it was significantly increased in group III and IV rat tissues. The study showed that garlic juice extract (100mg/kg b.w) and vitamin E (100mg/kg b.w) administration prevented oxidative damage in rat tissues treated with nicotine. The study also showed that vitamin E has a more potent antioxidant activity than garlic juice in preventing nicotine induced oxidative damage in rat. Keywords: Nicotine, Vitamin E, Garlic, antioxidant.     

Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats

Agaricus blazei Murill is one of the very popular edible medicinal mushrooms. The present study investigated the protective effect of this biologically active mushroom on the tissue peroxidative damage and abnormal antioxidant levels in carbon tetrachloride induced hepatotoxicity in male albino rats. Male albino rats of Sprague–Dawley strain weighting (120–150 g) were categorized into five groups. The first group served as the normal control, the second and the third groups were treated with Agaricus blazei Mushroom extract and carbon tetrachloride dose, respectively. Fourth group (protective group) was first treated with Agaricus blazei Mushroom extract followed by carbon tetrachloride treatment and fifth (therapeutic group) with carbon tetrachloride first followed by Agaricus blazei Mushroom treatment. The wet fruiting bodies of mushroom Agaricus blazei Murill, crushed and suspended in distilled water was administered orally to the treated groups of male albino rats. The activities of various enzymes (aspartate and alanine transaminase, lactate dehydrogenase, glutathione reductase), levels of non-enzymatic antioxidants (glutathione, vitamin C, vitamin E) and level of lipid peroxidation (malondialdehyde) were determined in the serum of all the experimental animals. Decrease in all the enzymes and non-enzymatic antioxidant, along with an increase in the lipid peroxidative index (malondialdehyde) was found in all the carbon tetrachloride treated rats as compared with normal controls. Also increase level of non-enzymatic antioxidant along with the decrease level in malondialdehyde was found in all experimental animals which were treated with Agaricus blazei Mushroom extract as compared with normal controls. The findings indicate that the extract of Agaricus blazei Murill can protect the liver against carbon tetrachloride induced oxidative damage in rats and is an efficient hepatoprotective and antioxidant agent against carbon tetrachloride induced liver injury.     

Alterations in antioxidant enzymes and oxidative damage in experimental diabetic rat tissues: Effect of vanadate and fenugreek (Trigonella foenum graecum)

With the premise that oxygen free radicals may be responsible for the severity and complications of diabetes, the level of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as the oxidative damage were examined in the tissues of control, diabetic and treated rats. After three weeks of diabetes, the activity of CAT was significantly increased in heart in diabetes (about 6-fold) but decreased in liver. The SOD activity decreased significantly in liver but increased in brain. The activity of GPx decreased significantly in liver and increased in kidney. A significant increase was observed in oxidative damage in heart and kidney and a small increase in brain with decrease in liver and muscle. Vanadate and fenugreek (Trigonella foenum graecum) administration to diabetic animals showed a reversal of the disturbed antioxidant levels and peroxidative damage. Results suggest that oxidative stress play a key role in the complications of diabetes. Vanadate and fenugreek seeds showed an encouraging antioxidant property and can be valuable candidates in the treatment of the reversal of the complications of diabetes.     

Zinc,iron, vitamin E,and erythrocyte stability in the rat

Previous studies have shown that deficiencies of zinc and vitamin E, as well as iron excess, contribute to peroxidative damage in several tissues in vivo. The present study reports on the sensitivity of red blood cells from young rats exposed to individual or concurrent imbalances of these three nutrients. For 21 d, rats were fed diets that were either deficient or replete in zinc and with or without excess iron or replete or deficient in vitamin E. When red blood cells from these rats were incubated in vitro, erythrocyte hemolysis, lipid peroxidation (assessed by MDA production), and hemoglobin degradation (assessed by alanine release), did not significantly increase unless vitamin E had been omitted from the diet. These results imply that either adequate tightly-bound zinc exists within the zinc-deficient cell to protect it from oxidative damage, or that other antioxidant defense mechanisms (including vitamin E) present within the plasma membrane and cytosol are sufficient to protect the cell from the otherwise damaging effects of zinc deficiency and/or iron excess.     

Rutin improves the antioxidant status in streptozotocin-induced diabetic rat tissues

Rutin, a polyphenolic flavonoid, was investigated for its antioxidant potential in streptozotocin (STZ)-induced diabetic rats. Rats were rendered diabetic by a single intraperitoneal injection of streptozotocin (50 mg/kg). The levels of fasting plasma glucose and insulin were estimated. Lipid peroxidative products and antioxidants were estimated in liver, kidney and brain. Histopathological studies were carried out in these tissues. A significant (p < 0.05) increase in the levels of fasting plasma glucose, lipid peroxidative products (thiobarbituric acid reactive substances [TBARS] and lipid hydroperoxides [HP]) and a significant (p < 0.05) decrease in plasma insulin, enzymic antioxidants (superoxide dismutase [SOD], catalase, glutathione peroxidase [GPx] and glutathione reductase [GRx]) and nonenzymic antioxidants (reduced glutathione [GSH], vitamin C and E) in diabetic liver, kidney and brain were observed. Oral administration of rutin (100 mg/kg) for a period of 45 days significantly (p < 0.05) decreased fasting plasma glucose, increased insulin levels and improved the antioxidant status of diabetic rats by decreasing lipid peroxidative products and increasing enzymic and nonenzymic antioxidants. Normal rats treated with rutin (100 mg/kg) showed no significant (p < 0.05) effect on any of the parameters studied. Histopathological studies of the liver, kidney and brain showed the protective role of rutin. Thus, our study clearly shows that rutin has antioxidant effect in STZ-induced experimental diabetes.     

Taurine attenuates hypertension and improves insulin sensitivity in the fructose-fed rat, an animal model of insulin resistance

Fructose feeding induces moderate increases in blood pressure levels in normal rats, which is associated with hyperinsulinemia, insulin resistance, and impaired glucose tolerance. Increased vascular resistance, sodium retention, and sympathetic overactivity have been proposed to contribute to the blood pressure elevation in this model. Taurine, a sulphur-containing amino acid, has been reported to have antihypertensive and sympatholytic actions. In the present study, the effects of taurine on blood pressure, plasma levels of glucose and insulin, glucose tolerance, and renal function were studied in fructose-fed rats. Fructose-fed rats had higher blood pressure and elevated plasma levels of insulin and glucose. The plasma glucose levels were higher in fructose-fed rats than in controls at 15, 30, and 60 min after the oral glucose load. Treatment with 2% taurine in drinking water prevented the blood pressure elevation and attenuated the hyperinsulinemia in fructose-fed rats. The exaggerated glucose levels in response to the oral glucose load was also prevented by taurine administration. Thus, taurine supplementation could be beneficial in circumventing metabolic alterations in insulin resistance.     

Taurine: Protective properties against ethanol-induced hepatic steatosis and lipid peroxidation during chronic ethanol consumption in rats

Summary Alcohol was administered chronically to female Sprague Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in hepatic steatosis and lipid peroxidation. Taurine, when co-administered with alcohol, reduced the hepatic steatosis and completely prevented lipid peroxidation. The protective properties of taurine in preventing fatty liver were also demonstrated histologically. Although alcohol was found not to affect the urinary excretion of taurine (a non-invasive marker of liver damage), levels of serum and liver taurine were markedly raised in animals receiving alcohol + taurine compared to animals given taurine alone. The ethanol-inducible form of cytochrome P-450 (CYP2E1) was significantly induced by alcohol; the activity was significantly lower than controls and barely detectable in animals fed the liquid alcohol diet containing taurine. In addition, alcohol significantly increased homocysteine excretion into urine throughout the 28 day period of ethanol administration; however, taurine did not prevent this increase. There was evidence of slight cholestasis in animals treated with alcohol and alcohol + taurine, as indicated by raised serum bile acids and alkaline phosphatase (ALP). The protective effects of taurine were attributed to the potential of bile acids, especially taurine conjugated bile acids (taurocholic acid) to inhibit the activity of some microsomal enzymes (CYP2E1). Thesein vivo findings demonstrate for the first time that hepatic steatosis and lipid peroxidation, occurring as a result of chronic alcohol consumption, can be ameliorated by administration of taurine to rats.     

Influence of 6-week exercise training on erythrocyte and liver antioxidant defense in hyperinsulinemic rats

High dosage of fructose in rats causes insulin resistance and hyperinsulinemia. This study investigates the effect of physical exercise on oxidant-antioxidant balance in rats fed a high fructose diet, which show characteristic features of insulin resistance. Products of lipid peroxidation and the activity of enzymic antioxidants namely superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase, in red blood cells (RBCs) and liver were assayed. Levels of non-enzymic antioxidants alpha-tocopherol and ascorbic acid and of protein and non-protein thiols were also determined. The levels of lipid peroxides, diene conjugates, lipofuscin and hydroperoxides were significantly higher in the liver of fructose-fed rats. The RBCs showed significantly higher susceptibility to H(2)O(2)-induced stress compared to control rats. Inadequate antioxidant system was noted in high fructose-fed rats. Physical training to these rats reversed the adverse effects, which could be important in alleviating the pathological consequences of insulin resistance.     

Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease

The incidence of obesity is now at epidemic proportions and has resulted in the emergence of nonalcoholic fatty liver disease (NAFLD) as a common metabolic disorder that can lead to liver injury and cirrhosis. Excess sucrose and long-chain saturated fatty acids in the diet may play a role in the development and progression of NAFLD. One factor linking sucrose and saturated fatty acids to liver damage is dysfunction of the endoplasmic reticulum (ER). Although there is currently no proven, effective therapy for NAFLD, the amino sulfonic acid taurine is protective against various metabolic disturbances, including alcohol-induced liver damage. The present study was undertaken to evaluate the therapeutic potential of taurine to serve as a preventative treatment for diet-induced NAFLD. We report that taurine significantly mitigated palmitate-mediated caspase-3 activity, cell death, ER stress, and oxidative stress in H4IIE liver cells and primary hepatocytes. In rats fed a high-sucrose diet, dietary taurine supplementation significantly reduced hepatic lipid accumulation, liver injury, inflammation, plasma triglycerides, and insulin levels. The high-sucrose diet resulted in an induction of multiple components of the unfolded protein response in the liver consistent with ER stress, which was ameliorated by taurine supplementation. Treatment of mice with the ER stress-inducing agent tunicamycin resulted in liver injury, unfolded protein response induction, and hepatic lipid accumulation that was significantly ameliorated by dietary supplementation with taurine. Our results indicate that dietary supplementation with taurine offers significant potential as a preventative treatment for NAFLD.     

Vitamin E inhibits hepatic oxidative stress, toxicity and hyperproliferation in rats treated with the renal carcinogen ferric nitrilotriacetate

Ferric nitrilotriacetate (Fe-NTA) is a potent renal and hepatic tumor promoter, which acts through a mechanism involving oxidative stress. Fe-NTA when injected intraperitoneally into rats induces hepatic ornithine decarboxylase activity as well as hepatic DNA synthesis. Vitamin E is a well-known, lipid-soluble and chain-breaking antioxidant which protects cell membranes from peroxidative damage. In this study, we investigated the protective effect of vitamin E, a major fat-soluble antioxidant, against Fe-NTA-mediated hepatic oxidative stress, toxicity and hyperproliferation in Wistar rats. Animals were treated with two different doses of vitamin E for 1 week prior to Fe-NTA treatment. Vitamin E at a higher dose of 2.0 mg/animal/day showed significant reduction in Fe-NTA-induced hepatic ornithine decarboxylase activity, DNA synthesis, microsomal lipid peroxidation and hydrogen peroxide generation. Fe-NTA treatment alone caused depletion of glutathione, glutathione metabolizing and antioxidant enzymes in rat liver, whereas pretreatment of animals with vitamin E reversed these changes in a dose-dependent manner. Taken together, our results suggest that vitamin E may afford substantial protection against the damage caused by Fe-NTA exposure and can serve as a potent preventive agent to suppress oxidant-induced tissue injury.     

High dietary salt decreases antioxidant defenses in the liver of fructose-fed insulin-resistant rats

In this study we investigated the hypothesis that a high-salt diet to hyperinsulinemic rats might impair antioxidant defense owing to its involvement in the activation of sodium reabsorption to lead to higher oxidative stress. Rats were fed a standard (CON), a high-salt (HS), or a high-fructose (HF) diet for 10 weeks after which, 50% of the animals belonging to the HF group were switched to a regimen of high-fructose and high-salt diet (HFS) for 10 more weeks, while the other groups were fed with their respective diets. Animals were then euthanized and their blood and liver were examined. Fasting plasma glucose was found to be significantly higher (approximately 50%) in fructose-fed rats than in the control and HS rats, whereas fat liver also differed in these animals, producing steatosis. Feeding fructose-fed rats with the high-salt diet triggered hyperinsulinemia and lowered insulin sensitivity, which led to increased levels of serum sodium compared to the HS group. This resulted in membrane perturbation, which in the presence of steatosis potentially enhanced hepatic lipid peroxidation, thereby decreasing the level of antioxidant defenses, as shown by GSH/GSSG ratio (HFS rats, 7.098±2.1 versus CON rats, 13.2±6.1) and superoxide dismutase (HFS rats, 2.1±0.05 versus CON rats, 2.3±0.1%), and catalase (HFS rats, 526.6±88.6 versus CON rats, 745.8±228.7 U/mg ptn) activities. Our results indicate that consumption of a salt-rich diet by insulin-resistant rats may lead to regulation of sodium reabsorption, worsening hepatic lipid peroxidation associated with impaired antioxidant defenses.     

Vitamin E inhibits hepatic oxidative stress,toxicity and hyperproliferation in rats treated with the renal carcinogen ferric nitrilotriacetate

Abstract

Ferric nitrilotriacetate (Fe-NTA) is a potent renal and hepatic tumor promoter, which acts through a mechanism involving oxidative stress. Fe-NTA when injected intraperitoneally into rats induces hepatic ornithine decarboxylase activity as well as hepatic DNA synthesis. Vitamin E is a well-known, lipid-soluble and chain-breaking antioxidant which protects cell membranes from peroxidative damage. In this study, we investigated the protective effect of vitamin E, a major fat-soluble antioxidant, against Fe-NTA-mediated hepatic oxidative stress, toxicity and hyperproliferation in Wistar rats. Animals were treated with two different doses of vitamin E for 1 week prior to Fe-NTA treatment. Vitamin E at a higher dose of 2.0 mg/animal/day showed significant reduction in Fe-NTA-induced hepatic ornithine decarboxylase activity, DNA synthesis, microsomal lipid peroxidation and hydrogen peroxide generation. Fe-NTA treatment alone caused depletion of glutathione, glutathione metabolizing and antioxidant enzymes in rat liver, whereas pretreatment of animals with vitamin E reversed these changes in a dose-dependent manner. Taken together, our results suggest that vitamin E may afford substantial protection against the damage caused by Fe-NTA exposure and can serve as a potent preventive agent to suppress oxidant-induced tissue injury.     

Hoe 140 abolishes the blood pressure lowering effect of taurine in high fructose-fed rats

Summary. High fructose feeding induces moderate increases in blood pressure of normal rats, associated with hyperinsulinemia, insulin resistance and impaired glucose tolerance. Increased vascular resistance, and sodium retention have been proposed to contribute to the blood pressure elevation in this model. Taurine, a sulphur-containing amino acid has been reported to have antihypertensive and antinatriuretic actions. In addition, taurine is shown to increase the excretion of nitrite and kinin availability and hence would be expected to improve the vascular tone. In the present study, the involvement of kinins in the blood pressure lowering effect of taurine was investigated by coadministration of Hoe 140, a kinin B₂ receptor antagonist along with taurine. The effects of taurine on plasma and urinary concentrations of sodium and tissue kallikrein activity were studied in high fructose-fed rats. Fructose-fed rats had elevated blood pressure and decreased levels of sodium in urine. Treatment with 2% taurine in drinking water prevented the blood pressure elevation and coadministration of Hoe 140 abolished this effect of taurine in high fructose-fed rats. The findings confirm the antinatriuretic action of taurine and also suggest a role for the kinins in the mechanism of taurine action in diet-induced hypertension.     

Effect of lead with vitamin E, C, or Spirulina on malondialdehyde, conjugated dienes and hydroperoxides in rats

Lead (100 ppm) was given in doubly deionised water for 30 days to one group of rats. The other groups received lead along with exogenous antioxidants like vitamin E (50 IU/kg), vitamin C (800 mg/kg) or Spirulina (1500 mg/kg) in food for a similar period. Levels of lipid peroxidation products such as malondialdehyde, conjugated diene and hydroperoxide were measured in liver, lung and kidney of treated rats. In lead treated animals there was a significant increase in the levels of these lipid peroxidative products. Administration of exogenous antioxidants in the lead treated animals reduced the levels of malondialdehyde, conjugated diene and hydroperoxide. It indicated that vitamin E, vitamin C and Spirulina had significant (P < 0.001) antioxidant activity thereby protecting the animals from lead induced toxicity.     

Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride

Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.     

Potential therapeutic effect of antioxidants in experimental diabetic retina: a comparison between chronic taurine and vitamin E plus selenium supplementations

Although good glycaemic control can delay the development and progression of diabetic retinopathy, new therapies are needed to obtain a better control of this diabetic complication. Oxidative stress seems to be a contributing factor in diabetic retinal alterations, therefore, it has been suggested that antioxidants may be beneficial in reducing diabetic retinal changes. However, many questions are still open. In fact, it remains to be ascertained which antioxidants are the most active when they are chronically administered in vivo and their effective dosages. Therefore, we compared the effect of chronic taurine supplementations versus a mixture of vitamin E + selenium on biochemical retinal changes induced by diabetes at different stages of the disease. Briefly, streptozotocin (STZ) diabetic rats were administered for 4 months following the dietary supplements: (a) 2% (w/w) taurine; (b) 5% (w/w) taurine; (c) 200 IU vitamin E + 8 mg selenium/kg diet (d) 500 IU vitamin E + 8 mg selenium/kg diet. In STZ diabetic rat in poor metabolic control (i.e. serum glucose >16.5 mmol/l), at 2, 4, 8, 16 weeks following the onset of diabetes, retinal conjugated dienes (CD) and lipid hydroperoxides (LP) were significantly and progressively increased, while sodium pump activity was gradually and significantly reduced. In taurine and vitamin E + selenium supplemented diabetic rats, glycaemia and body weight were not significantly different from those of non-supplemented diabetic animals. In diabetic rats, 2 and 5% taurine significantly decreased CD. This reduction is long lasting. Regarding CD, both vitamin E + selenium supplementations reduced CD only during the first 4 weeks of diabetes. Two percent taurine supplementation significantly lowered LP for the first 8 weeks of the disease while 5% taurine-induced-reduction lasted for the whole experimental time. A 200 IU vitamin E + 8 mg selenium supplementation did not significantly modify LP, while 500 IU vitamin E + 8 mg selenium significantly lowered them for the whole studied period. Finally, taurine preserved ATPase activity being more effective at 5% than 2%. Two hundred IU vitamin E + 8 mg selenium did not generally modify pump activity, while 500 IU vitamin E + 8 mg selenium partially prevented the decrease in pump activity. We conclude that taurine and vitamin E + selenium supplementations ameliorate biochemical retinal abnormalities caused by diabetes. These effects are dose- and time-dependent Moreover, the effect of taurine on CD is longer lasting than that of vitamin E + selenium. In addition, taurine seems to better preserve ATPase activity in comparison with vitamin E + selenium. Finally, in diabetic animals a negative correlation is found between CD and LP on one side and Na+K+ATPase activity on the other; thus, lipid peroxidation and pump activity seem to be associated. The same inverse correlations are present in vitamin E + selenium supplemented diabetic rats, but are lost in taurine supplemented animals. Therefore, taurine effects may not be simply mediated by its antioxidant activity. Thus, chronical (4 months) taurine and vitamin E + selenium supplementations reduce biochemical retinal alterations in diabetic rat in poor metabolic control.     

The effect of vitamin E on lipid peroxidation in the copper-deficient rat

The present study was designed to determine whether the supplementation of vitamin E in the copper-deficient diet would ameliorate the severity of copper deficiency in fructose-fed rats. Lipid peroxidation was measured in the livers and hearts of rats fed a copper-deficient diet (0.6 microg Cu/g) containing 62% fructose with adequate vitamin E (0.1 g/kg diet) or supplemented with vitamin E (1.0 g/kg diet). Hepatic lipid peroxidation was significantly reduced by vitamin E supplementation compared with the unsupplemented adequate rats. In contrast, myocardial lipid peroxidation was unaffected by the level of vitamin E. Regardless of vitamin E supplementation, all copper-deficient rats exhibited severe signs of copper deficiency, and some of the vitamin E-supplemented rats died of this deficiency. These findings suggest that although vitamin E provided protection against peroxidation in the liver, it did not protect the animals against the severity of copper deficiency induced by fructose consumption.