The effect of ascorbic acid supplementation on sperm quality, lipid peroxidation and testosterone levels of male Wistar rats

This study was conducted to investigate the effects of ascorbic acid supplementation in drinking water on semen quality, lipid peroxidation and plasma testosterone level of male rats. In this investigation, 24 male Wistar rats were used. The animals were divided into three group, and 500, 250 and 0 (control) mg/kg/day ascorbic acid were supplemented with drinking water of rats in Groups A, B and C during 8 weeks, respectively. Ascorbic acid supplementation did not increase in the body weight and weights of the testis, epididymis, seminal vesicles and ventral prostate. Exogenous supplementation with ascorbic acid significantly increased (P<0.05) the concentration of ascorbic acid in the testes and blood plasma, and the level of lipid peroxidation significantly decreased (P<0.05) in these locations. There was no significant difference in spermatozoon motility among the three groups. However, epididymal sperm concentration and plasma testosterone level significantly increased (P<0.05) in the ascorbic acid treated animals when compared to the control animals. The results suggest that ascorbic acid supplementation improves reproductive traits of male rats that are associated with high fertility.     

Chronic kidney disease with comorbid cardiac dysfunction exacerbates cardiac and renal damage

To address the pathophysiological mechanisms underlying chronic kidney disease with comorbid cardiac dysfunction, we investigated renal and cardiac, functional and structural damage when myocardial infarction (MI) was applied in the setting of kidney injury (induced by 5/6 nephrectomy—STNx). STNx or Sham surgery was induced in male Sprague–Dawley rats with MI or Sham surgery performed 4 weeks later. Rats were maintained for a further 8 weeks. Rats (n = 36) were randomized into four groups: Sham+Sham, Sham+MI, STNx+Sham and STNx+MI. Increased renal tubulointerstitial fibrosis (P < 0.01) and kidney injury molecule‐1 expression (P < 0.01) was observed in STNx+MI compared to STNx+Sham animals, while there were no further reductions in renal function. Heart weight was increased in STNx+MI compared to STNx+Sham or Sham+MI animals (P < 0.05), despite no difference in blood pressure. STNx+MI rats demonstrated greater cardiomyocyte cross‐sectional area and increased cardiac interstitial fibrosis compared to either STNx+Sham (P < 0.01) or Sham+MI (P < 0.01) animals which was accompanied by an increase in diastolic dysfunction. These changes were associated with increases in ANP, cTGF and collagen I gene expression and phospho‐p38 MAPK and phospho‐p44/42 MAPK protein expression in the left ventricle. Addition of MI accelerated STNx‐induced structural damage but failed to significantly exacerbate renal dysfunction. These findings highlight the bidirectional response in this model known to occur in cardiorenal syndrome (CRS) and provide a useful model for examining potential therapies for CRS.     

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.     

Anticoagulant Modulation of Blood Cells and Platelet Reactivity by Garlic Oil in Experimental Diabetes Mellitus

Multiple blood cell types and metabolic pathways involved in the modulation of platelet reactivity were investigated in streptozotocin-induced diabetic rats treated with garlic oil. Platelet counts of diabetic rats treated with garlic oil were significantly (P<0.01) reduced as compared to diabetic control rats. Garlic oil also increased the leucocyte counts of diabetic rats as compared to diabetic control rats. The significant (P<0.001) decreases by garlic oil of plasma concentration factors, V, VII, VIII: C, IX and X in diabetic rats may be interpreted to mean that there was a modulation of factor VII similar to that brought about by thrombin on factors V and VIII: C. This reversal of hypercoagulation through integrated biochemical reaction is suggestive of multicellular modulation of platelet reactivity, erythrocytes and neutrophils and the functional interactions between plasma coagulation factors and platelet cofactors.     

Sex hormones and aortic wall remodeling in an arteriovenous fistula

Background: An arteriovenous fistula (AVF) creates high blood flow through the artery and fistula. With this high flow, there is flow-induced remodeling and an increase in diameter, but no intimal hyperplasia. Estrogen has been shown to modify vascular remodeling, decreasing intimal hyperplasia after endothelial injury.Objective: These experiments tested the hypothesis that estrogen administration would decrease wall thickness in an AVE model. Because estrogen may decrease wall thickness, we also tested the hypothesis that testosterone would increase wall thickness.Methods: A fistula was created between the abdominal aorta and the inferior vena cava in Sprague-Dawley rats to generate high blood flow conditions in the aorta. Four groups of female animals were examined: sham, control with AVE ovariectomized (OVX) with AVE and OVX plus testosterone with AVE Four groups of male animals were also examined: sham, control with AVE castrated with AVE and castrated plus estrogen with AVE Five weeks after creation of the AVF, the aortas were collected and fixed; wall thickness was measured both proximal and distal to the AVEResults: Ovariectomy resulted in a significant decrease in estrogen levels (P < 0.01). Testosterone administration tended to increase testosterone levels in the OVX females, but values did not approach levels observed in the control males. No difference was noted in the proximal wall thickness between the control and the OVX animals. The OVX females receiving testosterone exhibited a significant increase in both proximal and distal wall thickness compared with control females (P < 0.001). In the male animals, there was no significant change in aortic wall thickness in the castrated rats compared with the controls. Estrogen administration in the castrated males resulted in a significant decrease in wall thickness in the proximal and distal aorta (P < 0.05).Conclusion: These studies suggest that, in a model of vascular remodeling, estrogen administration decreases wall thickness, and testosterone administration increases wall thickness.     

Selenium status of idiopathic infertile Nigerian males

Selenium concentration in the sera and seminal plasma of 60 infertile males (40 oligospermia and 20 azoospermia) and 40 males with proven evidence of fertility (normospermia; control group) were estimated using atomic absorption spectrophotometry. Results were correlated with spermatogram and hormonal levels in order to determine their relationship and significance in male infertility. The mean serum concentrations of selenium was found to be significantly increased in oligospermic compared to azoospermic subjects and controls (p<0.01), whereas the seminal plasma level was significantly higher in azoospermic compared to oligospermic subjects and controls (p<0.001). Thus, the ratio of serum selenium to seminal plasma selenium was 1∶1 in controls, 4∶1 in oligospermia, and 1∶2 in azoospermic subject. A significant inverse correlation was observed between serum selenium level and sperm count (p<0.01). Similarly, seminal plasma selenium correlated with spermatozoa motility, viability, and morphology. Serum selenium level shows positive correlation with the serum testosterone level (p<0.01). In conclusion, there appears to be a physiological balance in the distribution of selenium in serum and seminal plasma compartment of control males. A disturbance in this balance has a significant influence on spermatogenesis. Selenium appears to have a positive influence on Leydig cells, thus influencing the secretion of testosterone.     

Effects of Epiphyseal Proteins and Melatonin on Blood Biochemical Parameters of Fluoride-Intoxicated Rats

We examined the effects of fluoride intoxication on certain blood plasma biochemical indices in rats. Fortyeight adult female Wistar rats weighing 123-142 g were divided into eight groups: two control groups (0 and 28 days) and six experimental groups, namely sham-injected animals (vehicle), injected with pineal proteins (PP) and melatonin (Mel), intoxicated with fluoride (F), and also F+PP and F+Mel groups. Fluoride (150 ppm, per os administration with drinking water), melatonin (10 mg/kg, i.p.), and PP (100 μg/kg, i.p.) were administered daily for 28 days. Blood samples were collected at the end of experiments to estimate plasma [Na⁺] and [K⁺], alkaline phosphatase (ALP) activity, and levels of glucose and proteins in different animal groups. The plasma [K⁺] and [Na⁺], and ALP activity were significantly (P < 0.05) elevated in F-treated animals, as compared with others. Administration of PP and Mel in F-treated rats caused significant (P < < 0.05) reduction of [Na⁺], [K⁺], and ALP levels. Interestingly, PP and Mel administrations resulted in noticeable (P < 0.05) increases in the plasma glucose level in F-intoxicated animals, as compared to other groups. These findings convincingly indicate that PP and Mel exert ameliorative effects on fluoride-induced adverse changes in certain biochemical parameters in rats.     

Increased hepatic lipid soluble antioxidant capacity as compared to other organs of streptozotocin-induced diabetic rats: A cyclic voltammetry study

It has been suggested that oxidative stress plays an important role in the chronic complications of diabetes. The experimental findings regarding the changes in tissue antioxidant enzymes and lipid peroxidation of diabetic tissues have been inconsistent. Previous studies in our laboratory demonstrated that the reducing power of a specific tissue correlates with its low molecular weight antioxidant (LMWA) capacity. In the present study, the overall LMWA capacity (reducing equivalents) of plasma and tissues of streptozotocin (STZ)-induced diabetic rats (1–4 weeks) and insulin treated diabetic rats were measured by cyclic voltammetry. Levels of water and lipid soluble LMWA capacity progressively decreased in the diabetic plasma, kidney, heart and brain, while the diabetic liver, at 2, 3 and 4 weeks after STZ injection, showed a significant increase in the overall lipid soluble LMWA capacity (p < 0.001). Subsequently, analysis of specific components by high pressure liquid chromatography (electrochemical detection) showed decreased levels of ascorbic acid in plasma, kidney, heart and brain of diabetic animals. The α-tocopherol level dropped in all tissues, except for the liver in which there was a significant increase (p < 0.01 and p < 0.001 at 2–4 weeks). Lipid peroxidation was assessed by conjugated diene levels, which increased significantly in all diabetic tissues except the liver. Insulin treatment that was started after 3 weeks of diabetes and continued for 3 weeks showed no change in the conjugated dienes and in the overall LMWA capacity in all organs. Our results suggest a unique behavior of the liver in the STZ-induced diabetic rats to the stress and indicate its higher capacity to cope with oxidative stress as compared to other organs.     

Effect of Boron as an Antidote on Dry Matter Intake,Nutrient Utilization and Fluorine Balance in Buffalo (<Emphasis Type="Italic">Bubalus bubalis</Emphasis>) Exposed to High Fluoride Ration

Twenty male buffalo calves (8–9 months, 112.1 ± 7.69 kg) were divided into four groups of five animals in each and fed diets without (T1) or supplemented with 0.3 ppm selenium (Se) (T2), 0.3 ppm Se + 10 ppm copper (Cu) (T3), and 10 ppm Cu (T4) for 120 days during which blood samples were collected on day 0, 40, 80, and 120. Concentrations of glucose, total protein, urea, uric acid, and creatinine were similar in all the four groups, but the level of globulin was significantly (P < 0.01) increased in groups T2 and T3, leading to reduced levels of albumin and A:G ratio (P < 0.01) in these groups. The level of different serum enzymes viz. lactate dehydrogenase (LDH), alkaline phosphatase (ALP), glutamate pyruvate transaminase (SGPT), and glutamate oxaloacetate transaminase (SGOT) and hormones viz. T₃, T₄, testosterone and insulin and T₄:T₃ ratio were similar (P > 0.05) among the four groups. It was deduced that supplementation of 0.3 ppm Se and/or 10.0 ppm of Cu had no effect on blood metabolic profile in buffalo calves, except for an increased globulin level, indicating improved immunity status of these animals.     

Ghrelin improves disturbed myocardial energy metabolism in rats with heart failure induced by isoproterenol

To explore the effects of ghrelin on disturbed myocardial energy metabolism during chronic heart failure (CHF). Rats were subcutaneously injected with isoproterenol (ISO) for 10 days with or without ghrelin for another 10 days. Enzyme immunoassay was to measure ghrelin concentrations. Compared with the control group, ISO‐treated rats showed suppressed cardiac function with high ghrelin/GHS‐R expressions. These rats also showed the decreases in food consumption and weight. The decreased levels of plasma glucose and myocardial glucogen, but the high lactate in blood and myocardium showed myocardial metabolic disturbance. Compared with the group given ISO alone, the rats with ghrelin (20 and 100 µg/kg/day) improved cardiac dysfunction and increased food intake by 13.5 and 14.2% (both P < 0.01), and rate of weight gain by 95% (P < 0.05) and 1.71‐fold (P < 0.01), respectively. The plasma glucose were increased by 49.7 and 50.8% (both P < 0.01), and myocardial glucogen, by 40.5 and 51.7% (both P < 0.01), but blood lactate decreased by 1.56‐ and 1.96‐fold (both P < 0.01), and myocardial lactate by 32.1 and 48.7% (both P < 0.05), respectively. Their MCT1 mRNA and protein expressions increased. The myocardial ghrelin/GHS‐R pathway can be upregulated during CHF. The ghrelin can attenuate cardiac dysfunction and energy metabolic disturbance in CHF rats. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Adrenomedullin protects against fructose-induced insulin resistance and myocardial hypertrophy in rats

Adrenomedullin (ADM) has been recognized as a multipotent multifunctional peptide. To explore the pathophysiological roles of ADM in insulin resistance (IR), we studied the changes in ADM mRNA level in the myocardium and vessels and the effect of ADM supplementation on rats with IR induced by fructose feeding. Rats were fed 4% fructose in drinking water for 8 weeks, and ADM was administered subcutaneously in pure water through an Alzet Mini-osmotic Pump at 300 ng/kg/h for the last 4 weeks. Compared with controls, rats with IR showed increased levels of fasting blood sugar and serum insulin, by 95% and 67%, respectively (all P < 0.01), and glycogen synthesis and glucose transport activity of the soleus decreased by 54% and 55% (all P < 0.01). mRNA level and content of brain natriuretic peptide (BNP) in myocardial were all increased significantly. Fructose-fed rats showed increased immunoreactive-ADM content in plasma by 110% and in myocardia by 55% and increased mRNA level in myocardia and vessels (all P < 0.01). ADM administration ameliorated the induced IR and myocardial hypertrophy. The glycogen synthesis and glucose transport activity of the soleus muscle increased by 41% (P < 0.01) and 32% (P < 0.05). ADM therapy attenuated myocardial and soleus lipid peroxidation injury and enhanced the antioxidant ability. Our results showed upregulation of endogenous ADM during fructose-induced IR and the protective effect of ADM on fructose-induced IR and concomitant cardiovascular hypertrophy probably by its antioxidant effect, which suggests that ADM could be an endogenous protective factor in IR.     

Selenium and blood pressure studies in young and adult normotensive,renal, and spontaneously hypertensive animals

With reports of either no change or reduction of blood pressure, the relationship between selenium and blood pressure has not been clear. Normal Se values are not available for the Sprague Dawley (SD) rat or in the young and adult rat with various models of experimental hypertension. This study measured serum Se levels in the young and adult normotensive (NT), Grollman renal hypertensive (RH), and Okamoto-Aoki spontaneous hypertensive rats (SHR). The young animals have statistically significant (P<0.001) lower Se values as measured by the fluorometric method than those found at adulthood. Selenium levels were found to be altered in the adult SHR animals when compared with the RH and NT animals. The serum Se value for the normotensive SD rat was found to be 65.0±3.5 μg/dL, and for the two experimental models, 63.7±4.6 μg/dL for the RH, whereas the SHR level was elevated to 75.04±4.8 μg/dL (P<0.001). Elevated serum Se values in the adult SHR animals suggests an altered metabolism in SHR animals.     

Change and Significance of IL-8, IL-4, and IL-10 in the Pathogenesis of Terminal Ileitis in SD Rat

The objective of the study is to explore change and significance of IL-8, IL-4 and IL-10 in the pathogenesis of terminal Ileitis in SD rat. 60 male SD rats were divided into model group, suture group, and control group equally. The rats subjected to ileum-cecum side-to-side anastomosis in terminal ileum in model group, suture in terminal ileum in suture group, and the control group accepted no special treatment. The terminal ileum tissue which was 1–3 cm from anastomotic stoma was collected at 2 and 8 weeks after surgery in each group. The pathological slice was observed under microscope, and PCR was applied to detect the expression of IL-4, IL-8, and IL-10 at different times. Pathological result showed that neutrophils significantly increased in model group and suture group at 2nd week, showing acute inflammatory reaction; model group showed chronic inflammation at 8th week. The change of IL-8, IL-4, and IL-10 expression level at 2 weeks after surgery: The IL-8 expression level of SD rat terminal ileum tissue in model group was significantly higher than in control and suture groups (P < 0.01), and it was higher in suture group compared to control group (P < 0.01); the expression level of IL-4 in control group was higher than model and suture groups (P < 0.05); there was no statistical significance between model group and suture group (P = 0.363); the expression level of IL-10 in control group was higher than in model and suture groups (P < 0.01), and it was higher in suture group compared to model group (P < 0.01). The change of IL-8, IL-4, IL-10 expression level at 8 weeks after surgery: The expression level of IL-8 significantly decreased in model group, and there was no significantly difference between three groups (P > 0.05); the expression level of IL-4 was higher in model group and suture group compared to 2nd week; there was no significance between three groups (P < 0.05); the expression of IL-10 was higher in model group compared to 2nd week (P < 0.01), it was lower than control group and suture group (P < 0.01); there was no significant difference between suture group and control group (P > 0.05). The chronic terminal ileum model could be successfully established by ileum-cecum side-to-side anastomosis in terminal ileum in SD rats; IL-8 can induce the inflammatory reaction in terminal ileitis and chemokines aggregation and mediate inflammatory reaction by mediating other inflammatory factors; as a proinflammatory cytokine, IL-8 can inhibit IL-10; IL-10 and IL-4 can inhibit the inflammatory reaction of terminal ileum.     

Carbon Disulfide-Induced Changes in Cytoskeleton Protein Content of Rat Cerebral Cortex

To investigate the mechanism of carbon disulfide-induced neuropathy, male wistar rats were administrated by gavage at dosage of 300 or 500 mg/kg carbon disulfide, five times per week for 12 weeks. By the end of the exposure, the animals produced a slight or moderate level of neurological deficits, respectively. Cerebrums of carbon disulfide-intoxicated rats and their age-matched controls were Triton-extracted and centrifuged at a high speed (100,000 × g) to yield a pellet fraction of NF polymer and a corresponding supernatant fraction, which presumably contained mobile monomer. Then, the contents of six cytoskeletal protein (NF-L, NF-M, NF-H, α-tubulin, β-tubulin, and β-actin) in both fractions were determined by immunoblotting. Results showed that the contents of the three neurofilament subunits in the pellet and the supernatant fraction decreased significantly regardless of dose levels (P < 0.01). As for microtubule proteins, in the pellet fraction of cerebrum, the levels of α-tubulin and β-tubulin demonstrated some inconsistent changes. However, in the supernatant fractions, the content of α-tubulin and β-tubulin increased significantly in both two dose groups (P < 0.01). In comparison to neurofilament and tubulin proteins, the content of β-actin changed less markedly, only the supernatant fraction of the high dose group displayed significant increase (P < 0.01), but the others remained unaffected. These findings suggested that the changes of cytoskeleton protein contents in rat cerebrum were associated with the intoxication of carbon disulfide, which might be involved in the development of carbon disulfide neurotoxicity.     

Relationship between body iron stores and diquat toxicity in male Fischer-344 rats

The effects of body iron stores on diquat (DQ)-induced toxicity were examined in male Fischer-344 rats, which are sensitive to this herbicide. The rats (5 weeks old) were fed diets containing 40 (lower iron storage [LIS] group) or 320 ppm iron (higher iron storage [HIS] group) for 5 weeks. The concentrations of nonheme iron and ferritin in the liver and kidney were significantly higher in the HIS group than in the LIS group (P<0.0001), although there was no significant differences between the HIS and LIS groups in hematological parameters, including red blood cell count, hemoglobin concentration, and mean corpuscular volume. Three hours after administration of 0.1 mmol DQ/kg, serum alanine aminotransferase and urea nitrogen were significantly higher than in controls (saline injection) for both the LIS and HIS groups (P<0.01), and, after DQ injection, these parameters were significantly higher in the HIS group than in the LIS group (P<0.01). When the rats were injected with 0.075 or 0.1 mmol DQ/kg, the survival time was significantly shorter in the HIS group than in the LIS group (P<0.05). These findings suggest that higher body iron stores result in more severe DQ toxicity in Fischer-344 rats.     

Attenuation of estradiol on the reduction of striatal dopamine by amphetamine in ovariectomized rats

Amphetamine (AMPH) is a highly addictive drug of abuse which exhibits toxicity to dopaminergic neurons in long‐term abusers. Estrogen seems to show neuroprotection in dopamine (DA) deficit caused by AMPH. The present study was to investigate the effects of estradiol on the levels of striatal DA in ovariectomized (Ovx) rats treated with or without AMPH. Female rats were Ovx for 2 weeks before administration of AMPH (5 mg/kg/day, i.p.) with or without 17β‐estradiol benzoate (EB) (25 µg/kg/day, s.c.) for 7 days. The striatal tissues were collected, homogenized with DA mobile phase, and centrifuged. The concentrations of DA in the supernatants were detected by HPLC. The protein expressions of dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT‐2), and tyrosine hydroxylase (TH) were analyzed by Western blotting. The results indicated that AMPH could attenuate DA level significantly in striatum (P < 0.01). Comparing to control groups, administration of either EB or EB plus AMPH increased DA level (P < 0.01). The protein expression of striatal DAT was significant greater (P < 0.01) in rats treated with AMPH plus EB than AMPH treated animals. These results suggest that the DA levels in striatum can be enhanced by EB via an increase of DAT expression following administration of AMPH. J. Cell. Biochem. 108: 1318–1324, 2009. © 2009 Wiley‐Liss, Inc.     

Effects of raloxifene and estradiol on bone turnover parameters in intact and ovariectomized rats

This study was designed to investigate effects of raloxifene (RLX) and estradiol on bone formation and resorption in intact and ovariectomized (ovx) rat models. In the intact model, a total of 24 adult female rats were divided into three groups: Controls subcutaneously received saline alone. RLX (2 mg/kg) and estradiol (30 μg/kg) were injected to two groups of animals for a period of 6 weeks at two daily intervals. In the second model, rats (n = 24) were ovx and allowed to recover for a period of at least 3 weeks. Control group received vehicle alone. Remaining rats were divided into two groups and injected with RLX (2 mg/kg) and estradiol (30 μg/kg) for 6 weeks. Urine samples were collected from all animals 24 h after the last drug administration. Urinary deoxypyridinoline (DPD) was measured by ELISA. Serum parathyroid hormone (PTH), calcitonin, and osteocalcin levels were measured by immunoradiometric method. Serum concentrations of alkaline phosphatase (ALP), Ca, and inorganic phosphate were determined by enzymatic–colorimetric method. Lumbar vertebrae (L2) of all animals were dissected out and processed for histopathological evaluation. Removal of ovaries significantly elevated urinary DPD levels (p < 0.01) compared with intact controls. Treatment of both intact and ovx rats with estradiol resulted in significant decreases (p < 0.01) in DPD values. RLX administration had no significant effect in the intact rats, but it remarkably reduced bone turnover in the ovx animals (p < 0.001). Both estradiol and RLX produced conflicting effects on serum ALP, osteocalcin, and PTH levels in both animal models. These findings suggest that RLX exerts its protective effects by reducing bone resorption, similar to that of estradiol, in ovx rats.     

Effects of sodium-orthovanadate and<Emphasis Type="Italic">Trigonella foenum-graecum</Emphasis> seeds on hepatic and renal lipogenic enzymes and lipid profile during alloxan diabetes

Sodium-orthovanadate (SOV) and seed powder ofTrigonella foenum graecum Linn. (common name: fenugreek, family: Fabaceae) (TSP) besides being potential hypoglycemic agents have also been shown to ameliorate altered lipid metabolism during diabetes. This study evaluates the short-term effect of oral administration of SOV and TSP separately and in concert (for 21 days) on total lipid profile and lipogenic enzymes in tissues of alloxan diabetic rats. Diabetic rats showed 4-fold increase in blood glucose. The level of total lipids, triglycerides and total cholesterol in blood serum increased significantly during diabetes. During diabetes the level of total lipids increased significantly (P < 0001) in liver and in kidney by 48% and 55%, respectively, compared to control. Triglycerides level increased by 32% (P < 001) in liver and by 51% (P < 0005) in kidney, respectively, compared to control. Total cholesterol level also increased significantly in both liver and kidney (P < 0.01 andP < 0001, respectively). The activities of NADP-linked enzymes; namely glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and the activities of lipogenic enzymes namely ATP-citrate lyase ΜTP-CL) and fatty acid synthase (FAS) were decreased significantly in liver and increased in kidney during diabetes as compared to control. SOV and TSP administration to diabetic animals prevented the development of hyperglycemia and alteration in lipid profile in plasma and tissues and maintained it near normal. Maximum prevention was observed in the combined treatment with lower dose of SOV (0.2%) after 21 days. We are presenting for the first time effectiveness of combined treatment of SOV and TSP in amelioration of altered lipid metabolism during experimental type-I diabetes     

Effects of Nigella sativa and its Major Constituent, Thymoquinone on Sciatic Nerves in Experimental Diabetic Neuropathy

The aim of this study was designed to investigate the possible beneficial effects of Nigella sativa (NS) and thymoquinone (TQ) on histopathological changes of sciatic nerves in streptozotocin-induced diabetic rats. The rats were randomly allotted into one of four experimental groups: A (control), B (diabetic untreated), C (diabetic treated with NS) and D (diabetic treated with TQ); each group contain ten animals. B, C and D groups received streptozotocin (STZ) to induce diabetes. The rats in NS and TQ treated groups were given NS (in a dose of 400 mg/kg body weight) and TQ (50 mg/kg body weight) once a day orally by using intra-gastric intubation for 12 weeks starting 2 days after STZ injection, respectively. Blood and tissue samples were obtained for biochemical and histopathological investigation. The treatment of both NS and TQ caused a sharp decrease in the elevated serum glucose (P < 0.01, 0.05, respectively), and an increase in the lowered serum insulin concentrations (P < 0.01, 0.05, respectively), in STZ-induced diabetic rats. STZ induced a significant decrease in the area of insulin immunoreactive β-cells (P < 0.0001). NS (P < 0.001) and TQ (P < 0.01) treatment resulted in increased area of insulin immunoreactive β-cells significantly. To date, no histopathological changes of sciatic nerves in STZ induced diabetic rats by NS and TQ treatment have been reported. In this study, histologic evaluation of the tissues in diabetic animals treated with TQ and especially NS showed fewer morphologic alterations. Myelin breakdown decreased significantly after treatment with NS and TQ. The ultrastructural features of axons also showed remarkable improvement. We believe that further preclinical research into the utility of NS and TQ may indicate its usefulness as a potential treatment on peripheral neuropathy (PN) in STZ induced diabetic rats.