Acute renal failure (ARF) is the most frequent and a serious complication in victims of Russell’s viper snakebites. Russell’s viper venom-factor X activator (RVV-X) has been identified as a main procoagulant enzyme involving coagulopathy, which might be responsible for changes in renal hemodynamics and renal functions. Here, we purified RVV-X from crude Russell’s viper venom to study renal hemodynamics, renal functions, intravascular clot, and histopathological changes in Sprague–Dawley rats. Changes in renal hemodynamics and renal functions were evaluated by measuring the mean arterial pressure, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), effective renal blood flow (ERBF), renal vascular resistance (RVR), and fractional excretion of electrolytes. After 10 min, rats receiving both crude venom and purified RVV-X decreased GFR, ERPF, and ERBF and increased RVR. These changes correlated to renal lesions. Along with the determination of intravascular clot, rats injected with purified RVV-X increased the average D-dimer level and reached a peak at 10 min, declined temporarily, and then reached another peak at 30 min. The temporal association between clots and renal dysfunction was observed in rats within 10 min after the injection of purified RVV-X. These findings suggested RVV-X as a major cause of renal failure through intravascular clotting in the renal microcirculation.

BackgroundBlack cumin (Nigella sativa) is an ancient herbal medicine recommended by the World Health Organization. The antioxidant and antihyperglycemic effects of black cumin are well established. Amelioration of renal dysfunction in nephrotoxic rats with black cumin treatment has also been noted. However, the effect of black cumin treatment on renal dysfunction in diabetes mellitus has not been clarified. In this study, the effect of black cumin oil (BC) on changes in renal dysfunction and renal hemodynamics in streptozotocin-induced diabetic rats was evaluated.MethodsThe experiments were performed in male Sprague Dawley rats, divided into four groups (seven in each group): (1) normal rats given tap water (CON); (2) normal rats administered with BC (CON-BC); (3) diabetic rats given tap water only (STZ); and (4) diabetic rats administered with BC (STZ-BC). Diabetes mellitus was induced in the rats by an injection of streptozotocin. BC was given orally at the dose of 1000 mg/kg body weight to the rat in either CON-BC or STZ-BC every day for 8 weeks. Renal hemodynamics and functions in each rat were studied.ResultsRenal hemodynamic changes in STZ-BC rats appeared to increase in terms of glomerular filtration rate, effective renal plasma flow, and effective renal blood flow, while renal vascular resistance and filtration fraction were decreased in comparison with diabetic rats given tap water only (STZ). An improvement of renal tubular dysfunction in STZ-BC rats was indicated by the decreases in fractional excretion of water and Mg++.ConclusionAn administration of BC can restore changes in renal hemodynamics and renal dysfunction in streptozotocin-induced diabetic rats.

Background:Microangiopathy is a chronic diabetic complication resulting from metabolic derangements, oxidative stress, and increased pro-inflammatory cytokine production. Nigella sativa Linn. is used as an herbal medicine that exerts hypoglycemic, antilipidemic, anti-inflammatory, and antioxidant effects.Objective:To examine the effects of N. sativa extract on cutaneous microvascular changes in diabetic rats.Materials and Methods:Sprague-Dawley rats were randomly assigned into the following four groups: Untreated and N. sativa-treated normal controls and untreated and N. sativa-treated rats with streptozotocin-induced diabetes. A cold-pressed N. sativa extract was then orally administered (1000 mg/kg/day). After 8 weeks of treatment, the glucose, glycosylated hemoglobin (HbA1c), tumor necrosis factor-alpha (TNF-α), insulin levels, and lipid profile were determined in cardiac blood. Dermal capillary wall thickness was measured in tail skin sections stained with periodic acid-Schiff. Endothelial apoptosis was morphologically evaluated by hematoxylin and eosin staining.Results:Diabetes significantly reduced the circulating insulin and low-density lipoprotein levels and caused elevations in the glucose, HbA1c, and triglyceride levels, accompanied by a slight increase in total cholesterol levels and no change in the high-density lipoprotein and TNF-α levels. Capillary basement membrane thickening and a decreased capillary luminal diameter despite no evidence of endothelial cell apoptosis were also observed. N. sativa treatment of diabetic rats reduced the mean HbA1c concentration by 1.4%, enlarged the capillary lumens, and tended to attenuate dermal capillary basement membrane thickening without affecting the lipid profile or TNF-α level.Conclusion:Our results indicate that N. sativa may be used to minimize the risk of diabetic microangiopathy, potentially due in part to its glycemic control activity.SUMMARY Diabetes causes dermal capillary basement membrane thickening and a decreased capillary luminal diameterNigella sativa treatment of diabetic rats enlarged the capillary lumens and tended to attenuate dermal capillary basement membrane thickeningN. sativa treatment of diabetic rats reduced the mean glycosylated hemoglobin concentration by 1.4%, which exceeds the necessary reduction previously described to decrease the risk of diabetic microangiopathy, without affecting the lipid profile or tumor necrosis factor-alpha levelN. sativa improves rat diabetic microangiopathy, potentially due in part to its glycemic control activity. Abbreviations used: H and E: Hematoxylin and eosin, HbA1c: Glycosylated hemoglobin, HDL-C: High-density lipoprotein cholesterol, LDL-C: Low-density lipoprotein cholesterol, PAS: Periodic acid-Schiff, STZ: Streptozotocin,

Background: Oxidative stress induces renal dysfunction in diabetes, in which renal mitochondrial disturbance was implicated. Vitamin C (VC) supplementation may ameliorate the renal dysfunction in diabetics. However, it is not clear whether VC supplementation is effective for renal mitochondrial disturbances in diabetes. Objective: Investigate whether long-term continuous VC supplementation could ameliorate the renal mitochondrial disturbances in streptozotocin (STZ)-induced diabetic rats. Methods: Thirty-five male Sprague-Dawley rats were used, and diabetes was induced by an injection of STZ. The rats were divided into three groups: control rats (CON), STZ-induced diabetic rats (STZ), and diabetic rats supplemented by vitamin C (STZ-VC). The CON and STZ rats were given tap water, while STZ-VC rats received VC (1 g/L) every day for eight, 24 and 52 weeks. The kidney was isolated and homogenized. Oxygen comsumption (Vo2) was measured in mitochondria homogenate using an oxygen consumption monitor. Based on Vo2 tracings, the respiration control index (RCI) and P/O ratio (= ADP/ O ratio) were measured at week 8, 24 and 52. Results: At week eight, using either glutamate plus malate (for site I) or succinate (for site II) as substrates, both RCI and P/O ratio were not significantly different among three groups. The P/O ratio in STZ and STZ-VC rats increased from eight to 52 weeks after VC supplementation. At week 24, the P/O ratio at site II was normalized in STZ-VC rat. The increased P/O ratio (only site I) and the increased RCI (only site II) of STZ-VC rats were slower than those of STZ rats. Conclusion: Short-term VC supplementation might not influence the renal mitochondrial activity. The long-term VC supplementation could ameliorate the mitochondrial disturbances induced in STZ-induced diabetic rats.