Effect of bis[curcumino]oxovanadium complex on non-diabetic and streptozotocin-induced diabetic rats

The effect of the vanadium complex bis[curcumino]oxovanadium (BCOV) on blood glucose level, serum lipid levels, blood pressure and vascular reactivity were studied in non-diabetic and streptozotocin-induced diabetic (STZ-diabetic) rats and compared to that of vanadyl sulfate. Blood glucose level, serum lipid levels, and blood pressure were significantly increased in STZ-diabetic rats. Vascular reactivity to various agonists such as noradrenaline and acetylcholine were significantly increased in STZ-diabetic rats. Blood glucose and serum lipid levels were restored to normal in STZ-diabetic animals treated with vanadyl sulfate at a concentration of 0.5 mmol/kg/day (p.o.). However, vanadyl sulfate at a concentration of 0.2 mmol/kg/day (p.o.) did not produce any significant change in blood glucose and lipid levels. There was no significant effect of vanadyl sulfate (0.2 or 0.5 mmol/kg/day) treatment on blood pressure and vascular reactivity in STZ-diabetic rats. Vanadyl sulfate significantly reduced the body weight of non-diabetic and STZ-diabetic rats. Moreover, it also caused severe diarrhea in both groups of animals. Treatment with BCOV (0.05, 0.1 and 0.2mmol/kg/day, p.o.) significantly decreased blood glucose level and serum lipids in STZ-diabetic rats. Furthermore, administration of BCOV to STZ-diabetic rats restored the blood pressure and vascular reactivity to agonists to normal. There was no significant change in the body weight of BCOV treated non-diabetic and STZ-diabetic rats. Diarrhea was not observed in both BCOV treated groups. In conclusion, the present study shows that the vanadium complex BCOV has antidiabetic and hypolipedimic effects. In addition, it improves the cardiovascular complications associated with diabetes.     

Effects of vanadyl sulfate on kidney in experimental diabetes

The aim of this work was to investigate the biochemical and histological effects of vanadyl sulfate on blood glucose, urea, and creatinine in serum and nonenzymatic glycosylation and glutathione levels in kidney tissue of normal and streptozotocin (65 mg/kg) diabetic rats. Vanadyl sulfate was administered by gavage at a dose of 100 mg/kg. After 60 d of treatment, serum urea, creatinine, and blood glucose levels significantly increased in the diabetic group but not so in the vanadyl sulfate, which showed significantly reduced serum urea and blood glucose levels and a nonsignificant reduction of serum creatinine levels. Nonenzymatic glycosylation was increased and the glutathione level was decreased in the kidney tissue of diabetic rats. Treatment with vanadyl sulfate reversed these effects. Degenerative changes were detected in diabetic animals by electron and light microscopy. Although there are individual differences in diabetic animals given vanadium, some reduction of degenerative changes were observed.     

Vanadyl Sulfate Administration Protects the Streptozotocin-Induced Oxidative Damage to Brain Tissue in Rats

Diabetes mellitus manifests itself in a wide variety of complications and the symptoms of the disease are multifactorial. The present study was carried out to investigate the effects of vanadyl sulfate on biochemical parameters, enzyme activities and brain lipid peroxidation, glutathione and nonenzymatic glycosylation of normal- and streptozotocin-diabetic rats. Streptozotocin (STZ) was administered as a single dose (65 mg/kg) to induce diabetes. A dose of 100 mg/kg vanadyl sulfate was orally administered daily to STZ-diabetic and normal rats, separately until the end of the experiment, at day 60. In STZ-diabetic group, blood glucose, serum sialic and uric acid levels, serum catalase (CAT) and lactate dehydrogenase (LDH) activities, brain lipid peroxidation (LPO) and nonenzymatic glycosylation (NEG) increased, while brain glutathione (GSH) level and body weight decreased. In the diabetic group given vanadyl sulfate, blood glucose, serum sialic and uric acid levels, serum CAT and LDH activities and brain LPO and NEG levels decreased, but brain GSH and body weight increased.The present study showed that vanadyl sulfate exerted antioxidant effects and consequently may prevent brain damage caused by streptozotocin-induced diabetes.     

Zinc supplementation ameliorates glycoprotein components and oxidative stress changes in the lung of streptozotocin diabetic rats

Zinc (Zn) is a component of numerous enzymes that function in a wide range of biological process, including growth, development, immunity and intermediary metabolism. Zn may play a role in chronic states such as cardiovascular disease and diabetes mellitus. Zn acts as cofactor and for many enzymes and proteins and has antioxidant, antiinflammatory and antiapoptotic effects. Taking into consideration that lung is a possible target organ for diabetic complications, the aim of this study was to investigate the protective role of zinc on the glycoprotein content and antioxidant enzyme activities of streptozotocin (STZ) induced diabetic rat tissues. Female Swiss albino rats were divided into four groups. Group I, control; Group II, control + zinc sulfate; Group III, STZ-diabetic; Group IV, diabetic + zinc sulfate. Diabetes was induced by intraperitoneal injection of STZ (65 mg/kg body weight). Zinc sulfate was given daily by gavage at a dose of 100 mg/kg body weight every day for 60 days to groups II and IV. At the last day of the experiment, rats were sacrificed, lung tissues were taken. Also, glycoprotein components, tissue factor (TF) activity, protein carbonyl (PC), advanced oxidative protein products (AOPP), hydroxyproline, and enzyme activities in lung tissues were determined. Glycoprotein components, TF activity, lipid peroxidation, non enzymatic glycation, PC, AOPP, hydroxyl proline, lactate dehydrogenase, catalase, superoxide dismutase, myeloperoxidase, xanthine oxidase, adenosine deaminase and prolidase significantly increased in lung tissues of diabetic rats. Also, glutathione levels, paraoxonase, arylesterase, carbonic anhydrase, and Na⁺/K⁺- ATPase activities were decreased. Administration of zinc significantly reversed these effects. Thus, the study indicates that zinc possesses a significantly beneficial effect on the glycoprotein components and oxidant/antioxidant enzyme activities.     

Effects of vanadyl sulfate on liver of streptozotocin-induced diabetic rats

The aim of this study was to investigate the microscopic and biochemical effects of vanadyl sulfate on liver tissue of normal and streptozotocin (65 mg/kg) diabetic rats. Vanadyl sulfate was administered by gavage at a dose of 100 mg/kg. Degenerative changes were observed in diabetic animals by light and transmission electron microscopes. Although there were individual differences in diabetic animals to which vanadium was given, some reduction of degenerative changes were detected. After 60 d of treatment, serum aspartate and alanine transaminase, alkaline phosphatase, blood glucose levels, liver lipid peroxidation, and nonenzymatic glycosylation significantly increased, but liver glutathione levels significantly decreased in the diabetic group. On the other hand, treatment with vanadyl sulfate reversed these effects. As a result, it might be concluded that vanadyl sulfate has a protective effect on damage of liver of streptozotocin-induced diabetic rats.     

The Impact of Magnesium on Isometric Twitch Parameters and Resting Membrane Potential of the Skeletal Muscle in Diabetic Rats

To present the relationship between oral magnesium supplementation, blood glucose, and changes in isometric twitch parameters, resting membrane potential (RMP), in the gastrocnemius muscle in diabetic rats. Sixty rats were used in this study. The rats were divided into four groups: control (drinking tap water, Group I, n = 15), control with treated with magnesium sulfate (10 g/L) (Group II, n = 15), diabetic (Group III, n = 15), and diabetic with treated with magnesium sulfate (10 g/L) (Group IV, n = 15). In Group II and IV, the level of plasma magnesium was increased comparing to those of the control group (p < 0.05). Isometric twitch tensions were decreased significantly in the Group III, but Group IV isometric twitch tensions were increased significantly. Group IV RMP values were close to the Group I. Hyperglycemia decreases gastrocnemius muscle isometric twitch tension and increases RMP in diabetic rats. Magnesium treatment can prevent these diabetic complications.     

Vanadyl sulfate protects against streptozotocin-induced morphological and biochemical changes in rat aorta

The aim of this study was to investigate the protective effects of vanadyl sulfate on aorta tissue of normal and streptozotocin (STZ)-induced diabetic rats, morphologically and biochemically. The animals were made diabetic by an intraperitoneal injection of streptozotocin (65 mg/kg) and vanadyl sulfate (100 mg/kg) that was given every day for 60 days by gavage technique to rats. Under the light and transmission electron microscopes, hypertrophy of the vessel wall, focal disruption in the elastic lamellae, an increase in thickness of total aortic wall, tunica intima, subendothelial space and adventitial layer, and a disorganization in smooth muscular cells of the tunica media were observed in diabetic animals. The aorta lipid peroxidation (LPO) levels were significantly increased and the aorta glutathione (GSH) levels were significantly reduced in STZ diabetic rats. In diabetic rats administered vanadyl sulfate for 60 days, aorta LPO levels significantly decreased and the aorta GSH level significantly increased. In conclusion, in vivo treatment with vanadyl sulfate of diabetic rats prevented the morphological and biochemical changes observed in thoracic aorta of diabetic animals.     

Adverse cardiac responses to alpha-lipoic acid in a rat-diabetic model: possible mechanisms?

Alpha-lipoic acid (ALA) is widely used as an antioxidant for the treatment of diabetes and its complications; however, the pro-oxidant potential of ALA has recently been reported. This study was designed to investigate whether ALA supplementation could have pro-oxidant effects on cardiac tissues in normal and diabetic rats. Diabetes was induced by a single dose of streptozotocin (STZ; 55 mg/kg (intraperitoneal). Diabetic and normal rats were treated with ALA (100 mg kg^?1 day^?1) for 45 days. ALA supplementation resulted in oxidative protein damage as evident by significant reduction in the cardiac levels of protein thiol in ALA-treated normal rats (P?<?0.01) together with a significant elevation (P?<?0.001) in the plasma levels of advanced oxidation protein products in ALA-treated normal rats and in ALA?+?STZ-diabetic rats compared with the normal control rats. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has emerged as the major source of superoxide anion and enhanced oxidative damage in heart failure. ALA supplementation increased the myocardial immunoreactivity of p47phox subunit of NADPH oxidase in both normal nondiabetic and diabetic rats reflecting its pro-oxidant effect. Data showed that ALA supplementation failed to prevent cardiac complications in diabetic rats and led to cardiac toxicity in normal rats as indicated by pathological changes (cellular infiltration, fibrosis, and degeneration) and by the elevation of serum cardiac biomarkers compared with normal controls. The pro-oxidant effects of ALA suggest that careful selection of appropriate doses of ALA in reactive oxygen species-related diseases are critical.     

Vanadium and diabetes

We demonstrated in 1985 that vanadium administered in the drinking water to streptozotocin (STZ) diabetic rats restored elevated blood glucose to normal. Subsequent studies have shown that vanadyl sulfate can lower elevated blood glucose, cholesterol and triglycerides in a variety of diabetic models including the STZ diabetic rat, the Zucker fatty rat and the Zucker diabetic fatty rat. Long-term studies of up to one year did not show toxicity in control or STZ rats administered vanadyl sulfate in doses that lowered elevated blood glucose. In the BB diabetic rat, a model of insulin-dependent diabetes, vanadyl sulfate lowered the insulin requirement by up to 75%. Vanadyl sulfate is effective orally when administered by either single dose or chronic doses. It is also effective by the intraperitoneal route. We have also been able to demonstrate marked long-terrn effects of vanadyl sulfate in diabetic animals following treatment and withdrawal of vanadyl sulfate. Because vanadyl sulfate is not well absorbed we have synthesized and tested a number of organic vanaditun compounds. One of these, bismaltolato-oxovanadiurn IV (BMOV), has shown promise as a therapeutic agent. BMOV is 2-3x more potent than vanadyl sulfate and has shown less toxicity. Recent studies from our laboratory have shown that the effects of vanadium are not due to a decrease in food intake and that while vanadium is deposited in bone it does not appear to affect bone strength or architecture. The mechanism of action of vanadium is currently under investigation. Several studies indicate that vanadiun is a phosphatase inhibitor and that vanadium can activate serine/threonine kineses distal to tbe insulin receptor presumably by preventing dephosphorylation due to inhibition of phosphatases Short-term clinical trials using inorganic vanadium compounds in diabetic patients have been promising.     

Decrease of hypothalamic neuropeptide Y gene expression by vanadyl sulfate in streptozotocin-induced diabetic rats.

In an attempt to elucidate the effect of vanadium compounds on the gene expression of neuropeptide Y (NPY), vanadyl sulfate (VOSO4) was orally administrated at the dose of 1 mg/kg body weight into streptozotocin-induced diabetic rats (STZ-diabetic rats) three times daily for 1 week. We found a marked lowering of plasma glucose with a significant decrease of food and water intake in these STZ-diabetic rats treated with VOSO4, although the weight gain was unaffected. The increase of hypothalamic NPY, both the mRNA level and peptide concentration, in STZ-diabetic rats was also reduced by this oral treatment of VOSO4. However, similar treatment of VOSO4 in normal rats failed to modify the feeding behavior and hypothalamic NPY gene expression. These data suggest that decrease of hypothalamic NPY gene expression by VOSO4 is related to the recovery of hyperphagia in diabetic rats lacking insulin.     

Effect of vitamin E supplementation on diabetes induced oxidative stress in experimental diabetes in rats

Diabetes induced by streptozotocin (50 mg/kg body wt, i.p.) in the rats substantially increased the plasma glucose and malondialdehyde levels along with corresponding decrease in the antioxidants levels. Supplementation of vitamin E (200 mg/kg body wt., ip) for 5 weeks resulted in non-significant decrease in the blood glucose levels but plasma malondialdehyde levels were reduced to below normal levels. Plasma vitamin E, vitamin C, uric acid and red blood cell glutathione levels were also restored to near normal levels on vitamin E supplementation to diabetic rats as compared to control (diabetic) rats. The activities of antioxidant enzymes, catalase (EC 1.11.1.6), glutathione peroxidase (GSHPx EC 1.11.1.9), and glutathione reductase (GR EC 1.6.4.2) were also concomitantly restored to near normal levels by vitamin E supplementation to diabetic rats. The results clearly demonstrated that vitamin E supplementation augments the antioxidant defense mechanism in diabetes and provides evidence that vitamin E may have a therapeutic role in free radical mediated diseases.     

Iron-loaded cardiac myocytes stimulate cardiac myofibroblast DNA synthesis

Zinc is an essential nutrient with a wide range of functions and closely involved in a variety of enzymatic processes of importance in glucose, protein and lipid metabolism. Ghrelin is the endogenous ligand of the G protein coupled growth hormone secretagogue receptor. The regulatory mechanism that explain the biosynthesis and secretion of ghrelin in the gastrointestinal tract has not been clarified. This study was undertaken to examine the effect of zinc supplementation on the streptozotocin (STZ)-induced diabetic rats, which exhibits ghrelin production and secretion, and lipid metabolism on the gastrointestinal tract. The animals were divided into four groups. Group I: Non-diabetic untreated animals. Group II: Zinc-treated non-diabetic rats. Group III: STZ-induced diabetic untreated animals. Group IV: Zinc-treated diabetic animals. Zinc sulfate was given to some of the experimental animals by gavage at a dose of 100 mg/kg body weight every day for 60 days. In the zinc-treated diabetic group, the blood glucose levels decreased and body weight increased as compared to the diabetic untreated group. Zinc supplementation to STZ-diabetic rats revealed the protective effect of zinc on lipids parameters such as total lipid, cholesterol, HDL-cholesterol and atherogenic index. There is no statistically change in ghrelin-immunoreactive cells in gastrointestinal tissue. But, it has found that zinc supplementation caused a significant reduction in densities of ghrelin-producing cells of fundic mucosa of zinc-treated diabetic animals as compared to untreated, non-diabetic controls. Zinc supplementation may contribute to prevent some complications of diabetic rats, biochemically.     

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.     

Effect of troxerutin on insulin signaling molecules in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic adult male rat

Troxerutin is a trihydroxyethylated derivative of the flavonoid, rutin. It has been reported to possess the hepatoprotective, nephroprotective, antioxidant, anti-inflammatory, and antihyperlipidemic activities. Troxerutin treatment reduced the blood glucose and glycosylated hemoglobin levels in high-cholesterol-induced insulin-resistant mice and in type-2 diabetic patients. However, the mechanism by which it exhibits antidiabetic property was unknown. Therefore, the present study was designed to evaluate the effect of troxerutin on insulin signaling molecules in gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic rats. Wistar male albino rats were selected and divided into five groups. Group I: Control. Group II: High fat and sucrose-induced type-2 diabetic rats. Group III: Type-2 diabetic rats treated with troxerutin (150 mg/kg body weight/day orally). Group IV: Type-2 diabetic rats treated with metformin (50 mg/kg body weight/day orally). Group V: Normal rats treated with troxerutin (150 mg/kg body weight/day orally). After 30 days of treatment, fasting blood glucose, oral glucose tolerance, serum lipid profile, and the levels of insulin signaling molecules, glycogen, glucose uptake, and oxidation in gastrocnemius muscle were assessed. Diabetic rats showed impairment in insulin signaling molecules (IR, p-IRS-1^Tyr632, p-Akt^Ser473, β-arrestin-2, c-Src, p-AS160^Thr642, and GLUT4 proteins), glycogen concentration, glucose uptake, and oxidation. Oral administration of troxerutin showed near normal levels of blood glucose, serum insulin, lipid profile, and insulin signaling molecules as well as GLUT4 proteins in type-2 diabetic rats. It is concluded from the present study that troxerutin may play a significant role in the management of type-2 diabetes mellitus, by improving the insulin signaling molecules and glucose utilization in the skeletal muscle.     

Modulation of reproductive dysfunctions associated with streptozocin-induced diabetes by Artemisia judaica extract in rats fed a high-fat diet

We investigated the palliative effect of Artemisia judaica extract (AjE) on testicular deterioration induced by DM in high-fat diet/streptozocin (HFD/STZ)-injected rats. Forty rats were allocated to the following five groups: control, AjE, HFD/STZ, HFD/STZ-AjE, and HFD/STZ-metformin. HFD/STZ-diabetic rats showed a marked decrease in testicular weight and male sex hormones. There was significant suppression of testicular antioxidant enzymes and glutathione content in HFD/STZ-diabetic rats. However, rats that had received the STZ injection and the high-fat diet displayed increased malondialdehyde content and nitric oxide levels as well as tumour necrosis factor-alpha. High levels of Bax and low levels of Bcl-2 were detected after the STZ injection. Obvious pathological alterations were found in the testicular tissue of the HFD/STZ-diabetic rats. Thus, the administration of AjE attenuated the biochemical, molecular, and histopathological changes in the testes of the diabetic rats. The obtained findings showed that AjE treatment attenuated the diabetes-induced reprotoxicity in male rats via its antioxidant, anti-inflammatory, and antiapoptotic properties.

     

Telmisartan Ameliorates Neurotrophic Support and Oxidative Stress in the Retina of Streptozotocin-Induced Diabetic Rats

Neurodegeneration is an early event in the diabetic retina which may lead to diabetic retinopathy. One of the potential pathways in damaging retinal neurons is the activation of renin angiotensin system including angiotensin II type 1 receptor (AT1R) in the diabetic retina. The purpose of this study was to determine the effect of telmisartan, an AT1R blocker on retinal level of brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and tyrosine hydroxylase (TH), glutathione (GSH) and caspase activity in the diabetic rats. The dysregulated levels of these factors are known to cause neurodegeneration in diabetic retina. Three weeks streptozotocin induced diabetic rats were orally treated or untreated with telmisartan (10 mg/kg/day). After 4 weeks of treatments, the levels of BDNF and GSH were found to be increased systemically in the sera as well as in the retina of diabetic rats compared to untreated rats as measured by enzyme-linked immunosorbent assay and biochemical techniques (p < 0.05). The caspase-3 activity in the telmisartan treated diabetic retina was decreased compared to untreated diabetic rats (p < 0.05). Western blotting experiments showed the expression levels of BDNF, CNTF and TH were increased compared to untreated diabetic rats (p < 0.05). Thus, our findings show a beneficial effect of AT1R blocker telmisartan in efficiently increasing neurotrophic support, endogenous antioxidant GSH content, and decreasing signs of apoptosis in diabetic retina.     

Antiperoxidative and antioxidant effects of Casearia esculenta root extract in streptozotocin-induced diabetic rats

Oxidative stress is currently suggested to play as a pathogenesis in the development of diabetes mellitus. The present study was designed to evaluate the effect of Casearia esculenta root extract on oxidative stress-related parameters in streptozotocin (STZ) -induced diabetic rats. Antidiabetic treatment with C. esculenta root extract (45 days) significantly (p < .05) decreased thiobarbituric acid reactive substances (TBARS) and remarkably improved tissue antioxidants status such as glutathione (GSH), ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E) in liver and kidney of STZ-diabetic rats. In diabetics rats, the activities of enzymatic antioxidants such as superoxide dismutase (SOD, EC 1.11.1.1) catalase (CAT, EC 1.11.1.6) were decreased significantly while the activity of glutathione peroxidase (GPx, EC 1.11.1.9) decreased in the liver and increased in the kidney. The treatment of diabetic rats with C. esculenta root extract over a 45-day period returned these levels close to normal. These results suggest that C. esculenta root extracts exhibit antiperoxidative as well as antioxidant effects in STZ-induced diabetic rats.     

Ergogenic effect of dietary L-carnitine and fat supplementation against exercise induced physical fatigue in Wistar rats

L-carnitine (LC) plays a central role in fatty acid metabolism and in skeletal muscle bioenergetics. LC supplementation is known to improve physical performance and has become widespread in recent years without any unequivocal support to this practice. A scientific-based knowledge is needed, to understand the implications of LC supplementation on physical fatigue. In current study, we have explored synergistic effects of dietary LC and fat content against physical fatigue in rats. Ninety male Wistar rats were supplemented with different concentrations of LC (0.15, 0.3, and 0.5 %) and fat content (5, 10, and 15 %) through diet in different combinations. Our results elucidated that LC (0.5 %) along with 10 and 15 % fat diet supplemented rats showed significant ergogenic effect. The swimming time until exhaustion was increased by ~2- and ~1.5-fold in rats fed with 10 and 15 % fat diet containing LC (0.5 %). LC supplementation improved the energy charge by increasing the levels of ATP, tissue glycogen, reduced GSH, plasma triglyceride, plasma glucose levels, and enzymatic antioxidant status, i.e., superoxide dismutase, catalase, and glutathione peroxidase. LC supplementation also significantly reduced lipid peroxidation, lactic acid, plasma urea nitrogen, creatinine, creatinekinase, and lactate dehydrogenase levels in various tissues compared to its respective control group. Thus the present study indicates that LC ameliorates the various impairments associated with physical endurance in rats.     

Increased uncoupling protein-2 and -3 gene expressions in skeletal muscle of STZ-induced diabetic rats

Streptozotocin (STZ)-induced diabetic animals are vulnerable to cold stress. Uncoupling proteins (UCPs) play an important role in regulating thermogenesis. We investigated the gene expressions of UCPs in brown adipose tissue (BAT), white adipose tissue (WAT), liver and gastrocnemius muscle of STZ-diabetic rats using Northern blot. UCP-1, -2 and -3 mRNA expressions in BAT were all remarkably lower in STZ-diabetic rats than those in control rats. Both UCP-2 and -3 gene expressions in gastrocnemius muscle were substantially elevated in STZ-diabetic rats and insulin treatment restored UCP gene expressions to normal levels. These results suggest that in STZ-diabetic rats, the overexpression of UCP-2 and UCP-3 in skeletal muscle provides a defense against hypothermogenesis caused by decreased UCPs in BAT.     

The Effects of Levosimendan Exposure on Oxidant/Antioxidant Status and Trace Element Levels in the Pulmonary Artery of Rats

We investigated both the effect of levosimendan and the role of oxidant/antioxidant status and trace element levels in the pulmonary artery of rats. Fourteen male Wistar albino rats were randomly divided into two groups of seven animals each. Group 1 was not exposed to levosimendan and served as a control. Levosimendan (12 μg/kg) diluted in 10 ml 0.9 % NaCl was administered intraperitoneally to group 2. Animals of both groups were killed after 3 days, and their pulmonary arteries were harvested to determine changes in tissue oxidant/antioxidant status and trace element levels. The animals in both groups were killed 72 h after the levosimendan exposure treatment, and pulmonary arteries were harvested to determine levels of the lipid peroxidation product MDA and the antioxidant GSH as well as the decreased activity of antioxidant enzymes such as SOD, GSH-Px and CAT. It was found that MDA levels increased in pulmonary artery tissues of rats after levosimendan administration. The GSH level decreased in the pulmonary artery of rats after levosimendan treatment. Co, Mn, Fe, Cd and Pb levels were significantly higher (P < 0.001) and Mg, Zn and Cu levels significantly lower (P < 0.001) in the levosimendan group compared to the control group. These results suggest that levosimendan treatment caused an increase in free radical production and a decrease in antioxidant enzyme activity in the pulmonary artery of levosimendan-treated rats. It also caused a decrease or increase in the levels of many minerals in the pulmonary artery, which is an undesirable condition for normal pharmacological function.