Beneficial effects of Phellodendri Cortex extract on hyperglycemia and diabetic nephropathy in streptozotocin-induced diabetic rats

This study investigated the effect of Phellodendri Cortex extract on hyperglycemia and diabetic nephropathy in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into normal control (NC), diabetic control (DC), and diabetic treatment with Phellodendri Cortex extract (DP). Over a 4-week experimental period, Phellodendri Cortex extract was administered orally at 379 mg/kg BW/day. The final fasting serum glucose level, urine total protein level, and relative left kidney weight in the DP group were significantly lower than the DC group. Renal XO and SOD activities in the DP group were significantly lower than the DC group and renal CAT activity in the DP group was significantly higher than the DC group. Tubular epithelial change was reduced in the DP group compared to the DC group. These results indicated that Phellodendri Cortex can reduce glucose level and prevent or retard the development of diabetic nephropathy in streptozotocin-induced diabetic rats.     

Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy.

The effects of angiotensin converting enzyme inhibition with captopril were investigated in patients with diabetic nephropathy and hypertension. After nine days'' treatment with captopril glomerular filtration rate was unchanged in 13 patients, whereas renal plasma flow had increased from 265 to 302 ml/min/1.73 m2 body surface area (p less than 0.05) and the filtration fraction had decreased from 14.3 to 12.8% (p less than 0.025). During two years'' treatment with captopril in 14 patients the mean arterial blood pressure had fallen by 5 mm Hg (p less than 0.005) and the deterioration in glomerular filtration rate had decreased from 10.3 to 2.4 ml/min/year (p less than 0.005). There was no correlation between the fall in blood pressure and the reduction in the deterioration of glomerular filtration rate. These findings suggest that the effects of angiotensin converting enzyme inhibition on renal haemodynamics protect renal function. Inhibitors of angiotensin converting enzyme should be considered for lowering blood pressure in patients with diabetic nephropathy.     

Beneficial effects of ketogenic diet in obese diabetic subjects

Objective Obesity is closely linked to the incidence of type II diabetes. It is found that effective management of body weight and changes to nutritional habits especially with regard to the carbohydrate content and glycemic index of the diet have beneficial effects in obese subjects with glucose intolerance. Previously we have shown that ketogenic diet is quite effective in reducing body weight. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. In this study the effect of ketogenic diet in obese subjects with high blood glucose level is compared to those with normal blood glucose level for a period of 56 weeks. Materials and methods A total of 64 healthy obese subjects with body mass index (BMI) greater than 30, having high blood glucose level and those subjects with normal blood glucose level were selected in this study. The body weight, body mass index, blood glucose level, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, urea and creatinine were determined before and at 8, 16, 24, 48, and 56 weeks after the administration of the ketogenic diet. Results The body weight, body mass index, the level of blood glucose, total cholesterol, LDL-cholesterol, triglycerides, and urea showed a significant decrease from week 1 to week 56 (P < 0.0001), whereas the level of HDL-cholesterol increased significantly (P < 0.0001). Interestingly these changes were more significant in subjects with high blood glucose level as compared to those with normal blood glucose level. The changes in the level of creatinine were not statistically significant. Conclusion This study shows the beneficial effects of ketogenic diet in obese diabetic subjects following its long-term administration. Furthermore, it demonstrates that in addition to its therapeutic value, low carbohydrate diet is safe to use for a longer period of time in obese diabetic subjects.     

Beneficial effects of selenium on some enzymes of diabetic rat heart

It is known that selenium compounds can restore some metabolic parameters in experimental diabetes. However, as there are no, clear data about their effects on the altered antioxidant defense system of the diabetic heart, we aimed to investigate whether these beneficial effects extend to the alterations of some enzyme activities, which play important roles in antioxidant defense system. Diabetes was induced by streptozotocin (50 mg/kg body weight) and rats were then treated with sodium selenite (5 μmol/kg/d) for 4 wk. Sodium selenite treatment of the diabetic rats significantly restored the altered activities of glutathione- S-transferase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase, which are involved in the glutathione metabolism of the heart, but slightly but significantly decreased the high blood glucose level. In summary, the present study suggests that the beneficial effects of sodium selenite treatment appears to be the result of the restoration altered activities of the antioxidant enzymes in diabetic heart tissue.     

Beneficial effects of fenofibrate in pulmonary hypertension in rats

Viruses depend on cellular machinery to efficiently replicate. The host cytoskeleton is one of the first cellular systems hijacked by viruses in order to ensure their intracellular transport and promote the development of infection. Our previous results demonstrated that stable microfilaments and microtubules interfered with human influenza A/NWS/33 virus (H1N1) infection in semi-permissive LLC-MK2 cells. Although formins play a key role in cytoskeletal remodelling, few studies addressed a possible role of these proteins in development of viral infection. Here, we have demonstrated that mammalian Diaphanous-related formin-1 (mDia1) is involved in the control of cytoskeleton dynamics during human influenza A virus infection. First, by employing cytoskeleton-perturbing drugs, we evidenced a cross-talk occurring between microtubules and microfilaments that also has implications on the intracellular localization of mDia1. In influenza A/NWS/33 virus-infected LLC-MK2 cells, mDia1 showed a highly dynamic intracellular localization and partially co-localized with actin and tubulin. A depletion of mDia1 by RNA-mediated RNA interference was found to improve the outcome of influenza A/NWS/33 virus infection and to increase the dynamics of microfilament and microtubule networks in LLC-MK2 cells. Consistent with these findings, observations made in epithelial respiratory cells from paediatric patients with acute respiratory disease assessed that the expression of mDia1 is stimulated by influenza A virus but not by respiratory syncytial virus. Taken together, the obtained results suggest that mDia1 restricts the initiation of influenza A/NWS/33 virus infection in LLC-MK2 cells by counteracting cytoskeletal dynamics.     

Beneficial effect of vitamin E on the metabolic parameters of diabetic rats

The role of vitamin E in the pathogenesis of diabetes mellitus is unknown. The purpose of this study was to examine the effect of oral administration of vitamin E on some of the metabolic parameters of experimental diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (60 mg/kg body weight at 12 weeks of age). Vitamin E (0.2, 0.4, 0.8 mg/kg body weight) was administered orally for a period of 3 weeks to normal and diabetic Wistar rats. In some experiments, Vitamin E was given either before or after the induction of diabetes mellitus. Blood glucose level and weight were recorded for each rat in different groups on a weekly basis. Oral glucose tolerance test (OGTT) was performed on fasted normal, diabetic and vitamin E treated rats at the end of the experiment. Vitamin E significantly (p < 0.01) reduced blood glucose levels in experimental diabetes mellitus at all doses as compared to untreated rats. Vitamin E induced weight loss in normal as well as in diabetic rats. The beneficial effect of vitamin E on the hyperglycaemia of diabetic rats was dose-dependent. Moreover, vitamin E also improved OGTT in diabetic rats compared to untreated diabetics. In conclusion, vitamin E may play a role in glucose metabolism and thus be a useful adjuvant therapy in type I diabetes. (Mol Cell Biochem 261: 35–42, 2004)     

Insulin-mediated increase in sympathetic nerve activity is attenuated by C-peptide in diabetic rats

Connecting peptide (C-peptide) is secreted along with insulin in equimolar amounts into portal circulation in response to beta cell stimulation. The biological function of C-peptide had been mostly limited to establishing the secondary and tertiary structure of proinsulin. Recent studies have suggested that C-peptide can impact several functions, such as autonomic and sensory nerve function, insulin secretion, and microvascular blood flow. In this study we examined the effects of C-peptide in the presence or absence of insulin on cardiovascular and sympathetic nerve activity in both normal and streptozotocin (STZ)-induced diabetic Wistar rats. Animals were made diabetic by a single intravenous injection of STZ (50 mg/kg) and maintained for 6 weeks. The diabetic animals had higher plasma glucose, lower plasma insulin, and C-peptide, compared with the normal animals. To characterize cardiovascular and autonomic nervous responses, the animals were anesthetized with urethane/alpha-chloralose and instrumented for the recording of mean arterial pressure (MAP), heart rate (HR), and lumbar sympathetic nerve activity (LSNA). A bolus administration of C-peptide alone did not alter MAP, HR, or LSNA in normal or diabetic animals. The bolus administration of insulin alone increased HR and LSNA in normal and diabetic animals. However, the administration of insulin plus C-peptide attenuated the increase in HR in normals and the increase in LSNA in diabetic rats. We concluded that the C-peptides play a role in modulating the insulin-stimulated sympathetic nerve response.     

Beneficial effects of enalapril on chlorhexidine digluconate-induced liver peritoneal fibrosis in rats

Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of enalapril on chlorhexidine digluconate-induced liver PF by decreasing transforming growth factor-β1 (TGF-β1) production in rats. PF was induced in Sprague-Dawley rats by daily administration of 0.5 ml 0.1% chlorhexidine digluconate in normal saline via PD tube for one week. Rats received daily intravenous injections of low dose enalapril (1 mg/kg), or high dose enalapril (2.5 mg/kg), for one week. After 7 days, conventional 4.25% Dianeal (30 ml) was administered via a PD catheter with a dwell time of 4 h and assessment of peritoneal function. At the end of dialysis, the rats were sacrificed and liver peritoneum was harvested for microscopic examination and immunohistochemistry. There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D?/P?(urea) level was reduced, the D?/D? glucose level, serum and the dialysate TGF-β1 level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-β1, alpha-smooth muscle actin (α-SMA), fibronectin, collagen and vascular endothelial growth factor (VEGF) were elevated in the PF group compared with the vehicle group. High dose of enalapril decreased the serum and dialysate TGF-β1 levels, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-β1, α-SMA, fibronectin, collagen and VEGF-positive cells in the liver peritoneum. Low dose of enalapril did not protect against chlorhexidine digluconate-induced PF in the rat. Enalapril protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-β1 production.     

Beneficial effects of polyunsaturated fatty acids in partially nephrectomized rats

Evening primrose oil, safflower oil, and salmon oil, all with high polyunsaturated fatty acid content, were fed to partially nephrectomized rats; the effects were compared to those of feeding beef tallow. All three oils had favorable effects on progression of renal failure, salmon oil on kidney histology as well. The changes induced in platelet production of thromboxane A2, and in the renal production of various eicosanoids may explain the protective role of these oils.     

Beneficial effects of polyunsaturated fatty acids in partially nephrectomized rats

Evening primrose oil, safflower oil, and salmon oil, all with high polyunsaturated fatty acid content, were fed to partially nephrectomized rats; the effects were compared to those of feeding beef tallow. All three oils had favorable effects on progression on renal failure, salmon oil on kidney histology as well. The changes induced in platelet production of thromboxane A₂, and in the renal production of various eicosanoids may explain the protective role of these oils.     

Beneficial psychological effects of novel psychobiotics in diabetic rats: the interaction among the gut,blood and amygdala

Type 2 diabetes mellitus (T2DM) can lead to major complications such as psychiatric disorders which include depressive and anxiety-like behaviors. The association of the gut–brain axis in the development of such disorders, especially in T2DM, has been elucidated; however, gut dysbiosis is also reported in patients with T2DM. Hence, the regulation of the gut–brain axis, in particular, the gut–amygdala, as a vital region for the regulation of behavior is essential. Thirty-five male Wistar rats were divided into six groups. To induce T2DM, treatment groups received high-fat diet and 35 mg/kg streptozotocin. Then, supplements of Lactobacillus plantarum, inulin or their combination were administered to each group for 8 weeks. Finally, the rats were sacrificed for measurement of blood and tissue parameters after behavioral testing. The findings demonstrated the favorable effects of the psychobiotics (L. plantarum, inulin or their combination) on oxidative markers of the blood and amygdala (superoxide dismutase, glutathione peroxidase, malondialdehyde and total antioxidant capacity), as well as on concentrations of amygdala serotonin and brain-derived neurotrophic factor, in the diabetic rats. In addition, beneficial effects were observed on the elevated plus maze and forced swimming tests with no change in locomotor activity of the rats. There was a strong correlation between the blood and amygdala oxidative markers, insulin and fasting blood sugar with depressive and anxiety-like behaviors. Our results identified L. plantarum ATCC 8014 and inulin or their combination as novel psychobiotics that could improve the systemic and nervous antioxidant status and improve amygdala performance and beneficial psychotropic effects.     

Beneficial effects of melatonin on stroke-induced muscle atrophy in focal cerebral ischemic rats

MUSCLE ATROPHY IS THE RESULT OF TWO OPPOSING CONDITIONS THAT CAN BE FOUND IN PATHOLOGICAL OR DISEASED MUSCLES: an imbalance in protein synthesis and degradation mechanisms. Thus, we investigated whether exogenous melatonin could regulate muscle components in stroke-induced muscle atrophy in rats. Comparing muscle phenotypes, we found that long-term melatonin administration could influence muscle mass. Muscle atrophy-related genes, including muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF1) were significantly down-regulated in melatonin-administered rats in the gastrocnemius. However, only MAFbx at the mRNA level was attenuated in the soleus of melatonin-administered rats. Insulin-like growth factor-1 receptor (IGF-1R) was significantly over-expressed in melatonin-administered rats in both the gastrocnemius and soleus muscles. Comparing myosin heavy chain (MHC) components, in the gastrocnemius, expression of both slow- and fast-type isoforms were significantly enhanced in melatonin-administered rats. These results suggest that long-term exogenous melatonin-administration may have a prophylactic effect on muscle atrophy through the MuRF1/MAFbx signaling pathway, as well as a potential therapeutic effect on muscle atrophy through the IGF-1-mediated hypertrophic signaling pathway in a stroke animal model.     

Effect of unilateral nephrectomy on renal function of diabetic rats

Glomerular alterations of experimental diabetes mellitus are observed in animals submitted to a reduction in renal mass, suggesting that some mechanisms responsible for the progression of renal disease are common. The aim of this study was to investigate the effect of nephrectomy on the renal function and morphology of diabetic rats. Male Wistar rats were divided into 4 groups: control (C), n=8; diabetic (DM), n=8; non-diabetic nephrectomized (Nx), n=8; (DMNx), n=9. DM was induced by streptozotocin (65 mg/Kg), and animals were treated with insulin. After 12 weeks, the glomerular filtration rate (GFR), renal plasma flow (RPF) and mean arterial pressure (MAP) were evaluated in unanaesthetized animals. Glomerular volume (GV), glomerular sclerosis index (GSI), mesangial volume density (Vvmes) and glomerular capillary surface density (Svcap) were also evaluated. Results show that kidney weight increased in Nx groups, being higher in DMNx. GFR was higher in Nx groups as was RPF, being higher in DMNx. RVR was lower in Nx groups, especially in DMNx. MAP was not different among the groups. RPF and GFR showed a high correlation for the DMNx group (r=0.95, p=0.02). The DMNx group showed a correlation between RVR and GFR (r=-0.96, p=0.005). The GV increased in Nx groups, and the GSI was higher in DMNx. Vvmes and Svcap increased in DMNx group. In summary, Nx groups developed similar degrees of glomerular hypertrophy, but only DMNx showed an increased value for GSI. The present data suggest that the acceleration of glomerular lesions in DMNx animals was more closely associated to hemodynamic adaptations than to glomerular hypertrophy.     

Increased RhoA translocation in renal cortex of diabetic rats

RhoA, a member of the Rho small G protein family, mediates multiple intracellular signaling pathways, and is highly expressed in renal cortex. RhoA translocation is associated with RhoA activation. This study was undertaken to examine the relation of translocation of RhoA in the renal cortex with diabetic renal injury in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into control and diabetic groups and were studied at 8 weeks after STZ-injection (55 mg/kg, i.v). We found that the kidney weight and urinary protein excretion were significantly increased in diabetic rats. Diabetic glomerulopathy was confirmed by mesangial matrix expanding and glomerular basement membrane thickening. The ratio of membrane-bound RhoA verses cytosolic RhoA is 1.8 fold higher (p < 0.01) in diabetic group, indicating an enhanced RhoA translocation. There was no significant difference in total RhoA protein expression and RhoA mRNA expression between diabetic and control groups. These data suggest that RhoA translocation might be involved in diabetic renal injury.     

The effects of aminoguanidine on retinopathy in STZ-induced diabetic rats

BackgroundThe accumulation of advanced glycated end products (AGEs) in retinal blood vessels is one of the major etiological factors contributing to diabetic retinopathy. Aminoguanidine (AG) is one of the most extensively used inhibitors of AGEs formation. The aim of this study was to investigate whether AG could protect the development of diabetic retinopathy through inhibition of AGEs.MethodsRat diabetes was induced by intraperitoneal injection with streptozotocin (STZ). AG was given to rats in drinking water. Retina was extracted 3 and 6 months following STZ and AG administration. Immunochemistry and transmission electron microscope were used to detect the expression of AGEs and retina morphology.ResultsExtensive staining of AGEs was detected in retinal blood vessels of 3- and 6-month diabetic rats, while no significant staining was found in the control non-diabetic retina or AG treated groups. Pericyte loss, endothelial cell proliferation, increased ratio of endothelial cells/pericytes, acellular capillaries and capillary occlusion were observed in the retina of 6-month diabetic rats. The increased electron density of retinal capillary basement membrane, mitochondrial swelling in pericytes and endothelial cells were also found in 6-month diabetic rats. The 3-month diabetic rats and the AG-treated rats did not have similar morphological changes compared to control group. The AGEs staining in AG-treated rats was still weakly positive.ConclusionsAGEs plays pivotal roles in diabetic retinopathy. AGE deposition occurs prior to retinal microvasculature changes. AG could prevent the onset and development of diabetic retinopathy through inhibition of AGEs.     

Beneficial effects of Zingiber officinale Roscoe on fructose induced hyperlipidemia and hyperinsulinemia in rats

Fructose supplementation produced cardinal features of Syndrome-X including significant elevations in seum cholesterol, triglyceride, glucose and insulin and also in body weight. While treatment with methanolic extract of dried rhizomes of Zingiber officinale produced a significant reduction in fructose induced elevation in lipid levels, bodyweight, hyperglycemia and hyperinsulinemia, treatment with ethyl acetate extract of Z officinale did not poduce any significant change in either of the last two parameters. However, it produced a significant reduction in elevated lipid levels and body weight The concentration of 6-gingerol was found to be higher in methanolic extract and less in ethyl acetate extract. The results suggest that the methanolic extract of Z officinale produces better effects as compared to ethyl acetate extract in fructose induced hyperlipidemia associated with insulin resistance. The extent of activity appears to be dependent on the concentration of 6-gingerol present in the extracts.