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.     

Effects of selenium on altered mechanical and electrical cardiac activities of diabetic rat

Since selenium compounds can restore some metabolic parameters and structural alterations of diabetic rat heart, we were tempted to investigate whether these beneficial effects extend to the diabetic rat cardiac dysfunctions. Diabetes was induced by streptozotocin (50mg/kg body weight) and rats were then treated with sodium selenite (5 micromol/kg body weight/day) for four weeks. Electrically stimulated isometric contraction and intracellular action potential in isolated papillary muscle strips and transient (I(to)) and steady state (I(ss)) outward K(+) currents in isolated cardiomyocytes were recorded. Sodium selenite treatment could reverse the prolongation in both action potential duration and twitch duration of the diabetic rats, and also cause significant increases in the diminished amplitudes of the two K(+) currents. Treatment of rats with sodium selenite also markedly increased the depressed acid-soluble sulfhydryl levels of the hearts. Our data suggest that the beneficial effects of sodium selenite treatment on the mechanical and electrical activities of the diabetic rat heart appear to be due to the restoration of the diminished K(+) currents, partially, related to the restoration of the cell glutathione redox cycle.     

Amelioration of altered serum,liver, and kidney antioxidant enzymes activities by sodium selenite in alloxan-induced diabetic rats

Background:

The aim of this study was to evaluate the possible protective effect of sodium selenite on serum, liver, and kidney antioxidant enzymes activities in alloxan-induced type 1 diabetic rats.

Methods:

Forty Sprague-Dawley male rats were randomly divided into four groups; Group one as control, Group two as sham-treated with sodium selenite by 1 mg/kg intraperitoneal (i.p.) injections daily, Group three as diabetic untreated, and Group four as diabetic treated with sodium selenite by 1 mg/kg i.p. injections daily .Diabetes was induced in the third and fourth groups by subcutaneous alloxan injections. After eight weeks the animals were euthanized and livers and kidneys were immediately removed and used fresh or kept frozen until analysis. Before the rats were killed blood samples were also collected to measure glutathione peroxidase (GPX) and catalase (CAT) activities in sera.

Results:

Glutathione peroxidase and CAT activities serum, liver, and kidney were all significantly less in the diabetic rats than in the controls. Sodium selenite treatment of the diabetic rats resulted in significant increases in GPX activity in the kidneys and livers, and CAT activity in the sera and livers.

Conclusions:

Our results indicate that sodium selenite might be a potent antioxidant that exerts beneficial effects on both GPX and CAT activities in alloxan-induced type 1 diabetic rats. Key Words: Diabetes, Rat, Sodium selenite, Antioxidant enzymes activity     

Pentose phosphate pathway,glutathione-dependent enzymes and antioxidant defense during oxidative stress in diabetic rodent brain and peripheral organs: effects of stobadine and vitamin E

The aim of the present study was to investigate the effects of treatment with antioxidant stobadine (ST) on the activities of enzymes related with pentose phosphate pathway and glutathione-dependent metabolism and the other markers of oxidative stress in brain and peripheral organs of diabetic rats, and to compare the effects of ST treatment alone with the effects of treatments with another antioxidant vitamin E and ST plus vitamin E. Rats were made diabetic by the injection of streptozotocin (STZ; 55 mg/kg IP), and, 2 days later, some control and diabetic rats were left untreated or treated with ST (24.7 mg/kg/day, orally), vitamin E (400–500 U/kg/day, orally), or both substances together. In the brain, although 6-phosphogluconate dehydrogenase activity (6-PGD) did not change, glucose-6-phosphate dehydrogenase activity (G-6PD) was markedly increased in diabetic rats compared with controls; only combined treatment with ST and vitamin E produced a partial prevention on this alteration. The aorta G-6PD and 6-PGD of diabetic rats were 52% and 36% of control values, respectively. Neither single treatments with each antioxidant nor their combination altered the G-6PD and 6-PGD in aorta of diabetic rats. Glutathione peroxidase (GSHPx) activity was increased by STZ-diabetes in brain, heart, and kidney. In diabetic brain, vitamin E alone or combination with ST kept GSHPx at normal levels. Diabetes-induced stimulation in GSHPx did not decrease in response to the treatment with vitamin E in heart and kidney, but was greatly prevented by ST alone. The activity of glutathione reductase (GR) was decreased in brain and heart of diabetic rats. The treatment with each antioxidant or with a combination of both agents completely prevented this deficiency and resulted in further activation of GR in diabetic tissues. Glutathione S-transferase (GST) activity did not significantly change in diabetic brain and aorta. GST was stimulated by all treatment protocols in the brain of diabetic rats and was depressed in aorta of control rats. Catalase (CAT) was activated in diabetic heart but depressed in diabetic kidney. Diabetes-induced abnormalities in CAT activity did not respond to vitamin E alone in heart, was moderately ameliorated by the treatment with this vitamin in kidney, and was completely prevented by ST alone in both tissues. Superoxide dismutase (SOD) activity of brain and heart was unchanged by the diabetes but inhibited in diabetic kidney after the treatment ST alone or ST plus vitamin E. The lipid peroxidation (MDA) was increased in diabetic brain and heart. ST or vitamin E alone partly prevented diabetes-induced increase in MDA in brain and heart; however, antioxidant combination achieved a completely amelioration in MDA of these tissues of diabetic rats. Kidney MDA levels were similar in control and untreated diabetic animals. ST and vitamin E treatments, when applied separately or together, significantly reduced kidney MDA in both control and diabetic rats; and the combined effect of antioxidants was greater than that of each alone. These results are consistent with the degenerative role of hyperglycemia on cellular reducing equivalent homeostasis and antioxidant defense, and provide further evidence that pharmacological intervention of different antioxidants may have significant implications in the prevention of the prooxidant feature of diabetes and protects redox status of the cells.     

Efficacy of lower doses of vanadium in restoring altered glucose metabolism and antioxidant status in diabetic rat lenses

Vanadium compounds are potent in controlling elevated blood glucose levels in experimentally induced diabetes. However the toxicity associated with vanadium limits its role as therapeutic agent for diabetic treatment. A vanadium compound sodium orthovanadate (SOV) was given to alloxan-induced diabetic Wistar rats in lower doses in combination withTrigonella foenum graecum, a well-known hypoglycemic agent used in traditional Indian medicines. The effect of this combination was studied on lens morphology and glucose metabolism in diabetic rats. Lens, an insulin-independent tissue, was found severely affected in diabetes showing visual signs of cataract. Alterations in the activities of glucose metabolizing enzymes (hexokinase, aldose reductase, sorbitol dehydrogenase, glucose-6-phosphate dehydrogenase) and antioxidant enzymes (glutathione peroxidase, glutathione reductase) besides the levels of related metabolites, [sorbitol, fructose, glucose, thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH)]were observed in the lenses from diabetic rats and diabetic rats treated with insulin (2 IU/day), SOV (0.6 mg/ml),T. f. graecum seed powder (TSP, 5%) and TSP (5%) in combination with lowered dose of vanadium SOV (0.2 mg/ml), for a period of 3 weeks. The activity of the enzymes, hexokinase, aldose reductase and sorbitol dehydrogenase was significantly increased whereas the activity of glucose-6-phosphate dehydrogenase, glutathione peroxidase and glutathione reductase decreased significantly in lenses from 3 week diabetic rats. Significant increase in accumulation of metabolites, sorbitol, fructose, glucose was found in diabetic lenses. TBARS measure of peroxidation increased whereas the levels of antioxidant GSH decreased significantly in diabetic condition. Insulin restored the levels of altered enzyme activities and metabolites almost to control levels. Sodium orthovanadate (0.6 mg/ml) andTrigonella administered separately to diabetic animals could partially reverse the diabetic changes, metabolic and morphological, while vanadate in lowered dose in combination withTrigonella was found to be the most effective in restoring the altered lens metabolism and morphological appearance in diabetes. It may be concluded that vanadate at lowered doses administered in combination withTrigonella was the most effective in controlling the altered glucose metabolism and antioxidant status in diabetic lenses, these being significant factors involved in the development of diabetic complications, that reflects in the reduced lens opacity     

Regulation of liver and brain hexose monophosphate dehydrogenases by insulin and dietary intake in the female rat

Summary Liver glucose 6-phosphate dehydrogenase and phosphogluconate dehydrogenase activities were significantly decreased in both diabetic and fasted rats. Treatment of diabetic rats with insulin resulted in liver glucose 6-phosphate dehydrogenase and phosphogluconate dehydrogenase activities that were significantly greater than controls. Insulin promoted an increase in food consumption that was blocked by adrenaline. Insulin, when administered together with adrenaline, restored hepatic glucose 6-phosphate dehydrogenase and phosphogluconate dehydrogenas activities of diabetic animals to control values, without altering food consumption. Brain glucose 6-phosphate dehydrogenase and phosphogluconate dehydrogenase activities were not significantly altered by either dietary restriction, diabetes or insulin treatment. These results demonstrate a dissociation between the action of insulin on hepatic glucose 6-phosphate dehydrogenase activity and its action to increase food intake.Abbreviations NADP⁺ oxidoreductase, EC 1.1.1.49 Glucose 6-P dehydrogenase, GPD, D-glucose-6-phosphate - NADP⁺ 2-oxidoreductase (decarboxylating), EC 1.1.1.44 phosphogluconate dehydrogenase, PGD, 6-phospho-D-gluconate     

Aldehyde and Xanthine Oxidase Activities in Tissues of Streptozotocin-Induced Diabetic Rats: Effects of Vitamin E and Selenium Supplementation

Effects of vitamin E and selenium supplementation on aldehyde oxidase (AO) and xanthine oxidase (XO) activities and antioxidant status in liver, kidney, and heart of streptozotocin (STZ)-induced diabetic rats were examined. AO and XO activities increased significantly after induction of diabetes in rats. Following oral vitamin E (300 mg/kg) and sodium selenite (0.5 mg/kg) intake once a day for 4 weeks, XO activity decreased significantly. AO activity decreased significantly in liver, but remained unchanged in kidney and heart of vitamin E- and selenium-treated rats compared to the diabetic rats. Total antioxidants status, paraoxonase-1 (PON1) and erythrocyte superoxide dismutase activities significantly decreased in the diabetic rats compared to the controls, while a higher fasting plasma glucose level was observed in the diabetic animals. The glutathione peroxidase activity remained statistically unchanged. Malondialdehyde and oxidized low-density lipoprotein levels were higher in the diabetic animals; however, these values were significantly reduced following vitamin E and selenium supplementation. In summary, both AO and XO activities increase in STZ-induced diabetic rats, and vitamin E and selenium supplementation can reduce these activities. The results also indicate that administration of vitamin E and selenium has hypolipidemic, hypoglycemic, and antioxidative effects. It decreases tissue damages in diabetic rats, too.     

Effects of alpha-lipoic acid on biomarkers of oxidative stress in streptozotocin-induced diabetic rats

Increased oxidative stress and impaired antioxidant defense mechanisms are important factors in the pathogenesis and progression of diabetes mellitus and other oxidant-related diseases. This study was designed to determine whether alpha-lipoic acid, which has been shown to have substantial antioxidant properties, when administered (10 mg/kg ip) once daily for 14 days to normal and diabetic female Sprague-Dawley rats would prevent diabetes-induced changes in biomarkers of oxidative stress in liver, kidney and heart. Serum glucose concentrations, aspartate aminotransferase activity, and glycated hemoglobin levels, which were increased in diabetes, were not significantly altered by alpha-lipoic acid treatment. Normal rats treated with a high dose of alpha-lipoic acid (50 mg/kg) survived but diabetic rats on similar treatment died during the course of the experiment. The activity of glutathione peroxidase was increased in livers of normal rats treated with alpha-lipoic acid, but decreased in diabetic rats after alpha-lipoic acid treatment. Hepatic catalase activity was decreased in both normal and diabetic rats after alpha-lipoic acid treatment. Concentrations of reduced glutathione and glutathione disulfide in liver were increased after alpha-lipoic acid treatment of normal rats, but were not altered in diabetics. In kidney, glutathione peroxidase activity was elevated in diabetic rats, and in both normal and diabetic animals after alpha-lipoic acid treatment. Superoxide dismutase activity in heart was decreased in diabetic rats but normalized after treatment with alpha-lipoic acid; other cardiac enzyme activities were not influenced by either diabetes or antioxidant treatment. These results suggest that after 14 days of treatment with an appropriate pharmacological dose, alpha-lipoic acid may reduce oxidative stress in STZ-induced diabetic rats, perhaps by modulating the thiol status of the cells.     

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.     

Sodium Tungstate Attenuate Oxidative Stress in Brain Tissue of Streptozotocin-Induced Diabetic Rats

High blood glucose concentration in diabetes induces free radical production and, thus, causes oxidative stress. Damage of cellular structures by free radicals play an important role in development of diabetic complications. In this study, we evaluated effects of sodium tungstate on enzymatic and nonenzymatic markers of oxidative stress in brain of streptozotocin (STZ)-induced diabetic rats. Rats were divided into four groups (ten rats in each group): untreated control, sodium tungstate-treated control, untreated diabetic, and sodium tungstate-treated diabetic. Diabetes was induced with an intraperitoneal STZ injection (65 mg/kg body weight), and sodium tungstate with concentration of 2 g/L was added to drinking water of treated animals for 4 weeks. Diabetes caused a significant increase in the brain thiobarbituric acid reactive substances (P < 0.01) and protein carbonyl levels (P < 0.01) and a decrease in ferric reducing antioxidant power (P < 0.01). Moreover, diabetic rats presented a reduction in brain glucose-6-phosphate dehydrogenase (21%), superoxide dismutase (41%), glutathione peroxidase (19%), and glutathione reductase (36%) activities. Sodium tungstate reduced the hyperglycemia and restored the diabetes-induced changes in all mentioned markers of oxidative stress. However, catalase activity was not significantly affected by diabetes (P = 0.4), while sodium tungstate caused a significant increase in enzyme activity of treated animals (P < 0.05). Data of present study indicated that sodium tungstate can ameliorate brain oxidative stress in STZ-induced diabetic rats, probably by reducing of the high glucose-induced oxidative stress and/or increasing of the antioxidant defense mechanisms.     

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.     

Sodium Tungstate Administration Ameliorated Diabetes-Induced Electrical and Contractile Remodeling of Rat Heart without Normalization of Hyperglycemia

Recently, sodium tungstate was suggested to improve cardiac performance of diabetic rats in perfused hearts based on its insulinomimetic activity. In this study, we aimed to investigate the cellular and molecular mechanisms underlying this beneficial effect of sodium tungstate. Tungstate was administered (100 mg/kg/day) to diabetic and control rats intragastrically for 6 weeks. Blood glucose levels increased, whereas body weight, heart weight and plasma insulin levels decreased significantly in diabetic animals. Interestingly, none of these parameters was changed by tungstate treatment. On the other hand, fractional shortening and accompanying intracellular Ca(2+) [Ca(2+)](i) transients of isolated ventricular myocytes were measured, and sodium tungstate was found to improve the peak shortening and the amplitude of [Ca(2+)](i) transients in diabetic cardiomyocytes. Potassium and L-type Ca(2+) currents were also recorded in isolated ventricular cells. Significant restoration of suppressed I (to) and I (ss) was achieved by tungstate administration. Nevertheless, L-type calcium currents did not change either in untreated or treated diabetic rats. Tissue biochemical parameters including TBARS, protein carbonyl content, xanthine oxidase (XO) and xanthine dehydogenase (XDH) were also determined, and diabetes revealed a marked increase in TBARS and carbonyl content which were decreased significantly by tungstate treatment. Conversely, although XO and XDH activities didn't change in untreated diabetic rats, a remarkable but insignificant decrease was detected in treated animals. In conclusion, tungstate treatment improved diabetes-induced contractile abnormalities via restoration of dysregulated [Ca(2+)](i) and altered ionic currents. This beneficial effect is due to antioxidant property of sodium tungstate rather than normalization of hyperglycemia.     

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.     

Effect of selenite treatment on ultrastructural changes in experimental diabetic rat bones

It is known that streptozotocin (STZ)-induced diabetes causes functional and structural alterations in some types of tissue and organ. A number of methods have been used to characterize the properties of diabetic tissues and their diagnosis. Selenium compounds, playing an antioxidant role, can restore some altered metabolic parameters and diminished functions in experimental diabetes. The first aim of the present study was to investigate the effects of STZ-induced diabetes on structural properties of rat long bones. Electron and light microscopic observations showed deleterious alterations in the structure of the diabetic rat long bones, the most prominent effect being in osteocytic cells. Fine cytoplasmic processes of the osteocytes seemed to be shortened, and diabetes affected the normal cytoplasmic processes in a negative manner. The second aim of the present study was to evaluate the effects of sodium selenite treatment for 4 wk on the long bones of the diabetic rats. Electron and light microscopic observations demonstrated that sodium selenite treatment prevented the STZ-induced structural as well as ultrastructural changes in the long bones of the rats. In conclusion, this study first showed that a period of 5-wk diabetes was enough to cause some important and degenerative changes in the structure of the bone tissues, and, second, it demonstrated that sodium selenite treatment of the diabetic rats could normalize these alterations.     

Oxidative damage and antioxidant enzyme activities in experimental hypothyroidism

Free radicals are now well known to damage cellular components. To investigate whether age and thyroid level affect peroxidation speed, we examined the levels of malondialdehyde and antioxidant enzyme activities in different age groups of hypothyroid rats. Hypothyroidism was induced in 30- and 60-day-old Wistar Albino rats by the i.p. administration of propylthiouracil (10 mg kg(-1) body weight) for 15 days. While malondialdehyde levels of 30- or 60-day-old hypothyroid rats were increased in liver, they were decreased in the tissues of the heart and thyroid. While glucose-6-phosphate dehydrogenase activity levels did not change in heart, brain and liver tissues of 30-day-old rats, they increased in brain and heart tissues of 60-day-old experimental groups, but decreased in the liver. Catalase activities decreased in the liver and heart of rats with hypothyroidism, but increased in erythrocytes. In control groups while malondialdehyde levels increased in brain, heart and thymus with regard to age, they decreased in plasma. Glucose-6-phosphate dehydrogenase and catalase activities were not affected by age in tissues of the thymus, thyroid and brain, but they were decreased in the heart tissue. The changes in the levels of lipid peroxidation and antioxidant enzyme activities which were determined in different tissues of hypothyroid rats indicate a cause for functional disorder of these tissues. Moreover, there may be changes depending on age at lipid peroxidation and antioxidant enzyme activity levels.     

Protective effect of selenium treatment on diabetes-induced myocardial structural alterations

One of the main causes leading to mortality in diabetes is myocardial disease. Using streptozotocin (STZ)-induced diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Interstitial and microvascular disorders are known to be a characteristic part of the diabetic cardiomyopathy and partly resist insulin therapy. Because diabetic damage is partly attributed to oxidative stress, antioxidant treatment may be able to reduce this damage. The aim of this study was to investigate the cardioprotective effect of sodium selenite, known as an antioxidant agent. The diabetes was induced by ip injection of 50 mg/kg body wt STZ. The duration of diabetes was 5 wk. The protected group received (ip) 5 μmol/kg body wt/d sodium selenite (Na₂SeO₃) over 4 wk following diabetes induction. Electron and light microscopic morphometry of heart samples revealed typical diabetic alterations consisting in an increase in collagen content, vacuolation, diminishing of the cardiomyocyte diameter, alteration in myofilaments and Z-lines of myofibers, and myofibrillary degeneration. Sodium selenite treatment could prevent the loss of myofibrills and reduction of myocyte diameter. In the sodium-selenite-treated diabetic rat heart, alterations of the discus intercalaris and nucleus were corrected, and degenerations seen in myofilaments and Z-lines were reversed by this treatment. Under these findings, one can suggest that sodium selenite treatment may alleviate late diabetic complications when it is used under control conditions.     

Effects of dietary carbohydrate intake on antioxidant enzyme activity and copper status in the copper-deficient streptozotocin (STZ) diabetic rat

The aim of this study was to investigate how dietary lactose, compared with sucrose, in association with copper deficiency influences the antioxidant and copper status in the diabetic rat. Two groups of male rats (n = 12) were fed copper-deficient diets containing either 300 g/kg of sucrose or 300 g/kg of lactose in a pair-feeding regime for 35 days. Six rats from each group were injected with streptozotocin to induce diabetes. After a further 16 days the animals were killed and the liver, heart, and kidney removed for the measurement of copper levels and the activities of antioxidant and related enzymes. Diabetes resulted in higher hepatic and renal copper levels compared with controls. The copper content of the heart and kidney in diabetic rats consuming sucrose was also significantly higher than in those consuming lactose. Catalase activity in the liver, heart, and kidney was significantly increased in diabetic rats compared with controls. Hepatic glutathione S-transferase and glucose-6-phosphate dehydrogenase and cardiac copper zinc superoxide dismutase activities were also higher in diabetes. Sucrose, compared with lactose feeding, resulted in higher cytochrome c oxidase and glutathione peroxidase activities in the kidney while glucose-6-phosphate dehydrogenase activity was lower. The combination of lactose feeding and diabetes resulted in significantly higher activities of cardiac managanese superoxide dismutase and catalase and renal manganese superoxide dismutase and glucose-6-phosphate dehydrogenase. These results suggest that sucrose consumption compared with lactose appears to be associated with increased organ copper content and in general decreased antioxidant enzyme activities in copper-deficient diabetic rats.     

Changes in glucose metabolism from discrete regions of rat brain and its relationship to reproductive failure during experimental diabetes

This study reports the effects of alloxan induced diabetes on glucose metabolism enzymes viz. Hexokinase, Lactate dehydrogenase, and Glucose-6-phosphate dehydrogenase from discrete brain regions. Enzymes activity was assayed from hypothalamic areas such as medial preoptic area and median eminence-arcuate region which have gonadotropin releasing hormone cell bodies and their terminals, respectively and other brain regions like septum, amygdala, hippocampus, and thalamus. In all the areas studied, induction of diabetes resulted in a significant decrease in particulate bound HK activity, whereas soluble HK, LDH and G6PDH activity showed increase at 3, 8, 15 and 28 days intervals. Insulin treatment of diabetic rats led to recovery in enzyme activity. Blood glucose levels increased significantly after induction of diabetes and recovery was seen after insulin treatment. The present results suggest that altered cerebral glucose metabolism may also be responsible for reproductive failure observed in diabetic rats. (Mol Cell Biochem141: 97–102, 1994)     

Gender related differential effects of Omega-3E treatment on diabetes-induced left ventricular dysfunction

The present study was designed to determine whether there are beneficial effects of intake of Ω-3E (containing 70% pure omega-3 and 2% natural vitamin E) in cardiac dysfunction of diabetic rats. We also examined whether there are gender-related differences in the responses to the intake of Ω-3E on the heart dysfunction. Experiments were performed by using Langendorff-perfused hearts from normal, diabetic (with 50 mg/kg streptozotocin), and Ω-3E (50 mg/kg body weight/day) treated diabetic 3-month-old Wistar rats. Ω-3E treatment of the diabetics caused small, but significant decrease (13% and 14% female versus male) in the blood glucose level. Ω-3E treatment of the diabetic female rats did not prevent diabetes-induced decrease in left ventricular developed pressure (LVDP) and increase in left ventricular end-diastolic pressure (LVEDP) with respect to the control female rats. On the other hand, the treatment of diabetic male rats caused significant recovery in depressed LVDP. Furthermore, such treatment of diabetic female and male rats caused significant recovery in depressed rates of changes of developed pressure. This effect was more significant in males. Besides, Ω-3E caused significant further lengthening in the diabetes-induced increased time to the peak of the developed pressure in females, while it normalized the lengthening in the relaxation of the developed pressure in diabetic males. In addition, Ω-3E treatment caused significant restorations in the diabetes-induced altered activities of antioxidant enzymes without any significant gender discrepancy. Present data show that there are gender related differences in diabetic heart dysfunction and the response to antioxidant treatment.     

Effect of tangeretin,a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats

The present study was designed to evaluate the antihyperglycemic potential of tangeretin on the activities of key enzymes of carbohydrate and glycogen metabolism in control and streptozotocin induced diabetic rats. The daily oral administration of tangeretin (100 mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of tangeretin. Further, tangeretin administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of tangeretin in diabetic rats. The effect produced by tangeretin on various parameters was comparable to that of glibenclamide – a standard oral hypoglycemic drug. Thus, these results show that tangeretin modulates the activities of hepatic enzymes via enhanced secretion of insulin and decreases the blood glucose in streptozotocin induced diabetic rats by its antioxidant potential.