Microcystin-LR exposure interfered maintenance of colonic microenvironmental homeostasis in rat.

Microcystin-leucine arginine (MCLR) is a phycotoxin produced by cyanobacteria. As a hepatotoxin, increasing evidence suggests that it has some negative effects on the mammal gastrointestinal tract, but further studies are warranted. In this study, we investigated the effects of MCLR on the intestinal epithelial microenvironment by oral administration of MCLR. As expected, MCLR at doses of 200 and 400 µg kg-1 bw showed hepatorenal toxicity in rats but without significant gastrointestinal symptoms. MCLR exposure decreased the thickness of the colonic epithelial mucus layer, and down-regulated the expression of main mucin protein (MUC2), cytoskeletal assembly-related genes (Arpc1a, Enah) and cytoskeletal stability-related genes (Ptk2, Prkca, Actn1, Pxn, Tln1, Cttn, Vcl) in colonic tissue to varying degrees, but did not affect the expression of cell connection-related genes including Zo1, Ocln, Cldn2 and Cdh1. In addition, MCLR exposure had a limited effect on gut bacterial diversity but clearly enriched specific bacteria. Prevotella, which plays a crucial role in balancing health and disease, was inhibited, whereas Muribaculaceae concerning the epithelial barrier, was promoted. Together, our findings demonstrate that MCLR exposure can weaken the colonic epithelial barrier by interfering with the stability of the cytoskeleton, which in turn exacerbates the homeostasis maintenance in the intestinal microenvironment.

Effect of Endogenous Arginine-Vasopressin Arising from the Paraventricular Nucleus on Learning and Memory Functions in Vascular Dementia Model Rats.

The hippocampus is a key structure for encoding and processing memory and for spatial orientation, which are among the cognitive functions most sensitive to cerebral ischemia, hypoxia, and vascular dementia (VD). Since hippocampal formation is one of the principle forebrain targets for arginine-vasopressin (AVP) innervations arising in the hypothalamic paraventricular nucleus (PVN), we explored the contributions of AVP to VD pathogenesis. To this end, we randomly assigned pathogen-free, male Wistar rats to one of seven groups in a VD model and tested AVP treatment effects on spatial learning and memory using the Morris water maze. We also measured the superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration in brain samples and monitored the expression of AVP-positive neurons in the hippocampus by immunohistochemistry. The VD model with repeated cerebral ischemia-reperfusion injury evoked impairment of cognitive function and reduced cerebral concentrations of the antioxidation markers. Lesioning the rat PVN showed a similar effect on learning and memory and reduced antioxidation markers in the brain tissue. However, AVP injection into the PVN improved cognitive performance in VD rats, while enhancing/rectifying the changes in antioxidation markers. We conclude that our VD model may decrease AVP secretion in the PVN and subsequently reduce antioxidant capacity in the hippocampus, leading to impaired cognitive function.

Ameliorative effect of berberine on renal damage in rats with diabetes induced by high-fat diet and streptozotocin.

Berberine (BBR) is one of the main constituents in Rhizoma coptidis and it has widely been used for the treatment of diabetic nephropathy. The aims of the study were to investigate the effects and mechanism of action of berberine on renal damage in diabetic rats. Diabetes and hyperglycaemia were induced in rats by a high-fat diet and intraperitoneal injection of 40 mg/kg streptozotocin (STZ). Rats were randomly divided into 5 groups, such as i) control rats, ii) untreated diabetic rats iii) 250 mg/kg metformin-treated, iv and v) 100 and 200 mg/kg berberine-treated diabetic rats and treated separately for 8 weeks. The fasting blood glucose, insulin, total cholesterol, triglyceride, glycosylated hemoglobin were measured in rats. Kidneys were isolated at the end of the treatment for histology, Western blot analysis and estimation of malonaldehyde (MDA), superoxide dismutase (SOD) and renal advanced glycation endproducts (AGEs). The results revealed that berberine significantly decreased fasting blood glucose, insulin levels, total cholesterol, triglyceride levels, urinary protein excretion, serum creatinine (Scr) and blood urea nitrogen (BUN) in diabetic rats. The histological examinations revealed amelioration of diabetes-induced glomerular pathological changes following treatment with berberine. In addition, the protein expressions of nephrin and podocin were significantly increased. It seems likely that in rats berberine exerts an ameliorative effect on renal damage in diabetes induced by high-fat diet and streptozotocin. The possible mechanisms for the renoprotective effects of berberine may be related to inhibition of glycosylation and improvement of antioxidation that in turn upregulate the expressions of renal nephrin and podocin.

[Effects and mechanism of berberine on the hypertensive renal injury rats induced by enriched high fat-salt-fructose diet].

OBJECTIVE: To study the effects of berberine on hypertensive renal injury model in rats fed by enriched high fat-salt-fructose diet . METHODS: hypertensive renal injury model was esteblished by feeding enriched high fat-salt-fructose diet for 8 weeks. On the basis of animal blood pressure, hypertensive rats were randomly divided into model group (10 rats, distilled water), captopril group (10 rats,25 mg/kg), berberine high dose group (10 rats, 300 mg/kg) and low dose group (10 rats, 100 mg/kg). These rats were fed by enriched high fat-salt-fructose diet and treated by intragastric administration with drugs for 4 weeks. And normal control group (10 rats) was set Blood pressure was determined at 0, 4, 8, 10, 12 weekend,and after 4 weeks of drugs treatment, getting urine to determine urine protein, taking blood serum to determine blood urea nitrogen, serum creatinine,GHb,MDA and activity of SOD. The content of H2O2 and GSH-Px and activity of CAT in kidney tissues were determined also. RESULTS: Compared with normal control group, blood pressure, urine protein, blood urea nitrogen, serum creatinine and MDA and GHb in serum of model rats obviously increased (P < 0.01), the activity of SOD decreased (P < 0.01), higher content of H2O2 and lower content of GSH-Px and activity of CAT (P < 0.01) in the kidney tissues. Treated with berberine for 4 weeks, elevated blood pressure and heightened levels of urine protein, blood urea nitrogen and serum creatinine in model rats were depressed significantly (P < 0.01), and elevated the activity of SOD, lowed the levels of MDA and GHb in blood serum (P < 0.01). At the same time, berberine increased the activities of GSH-Px and CAT (P < 0.01) and slightly lowed the content of H2O2 in the kidney tissues. CONCLUSION: Berberine has protecting effects on the hypertensive renal impairment model rats fed by enriched high fat-salt-fructose diet, which are concerned with elevated antioxidant capability in body and kidney tissues.