Antihyperglycemic, antihyperlipidemic, and renoprotective effects of Chlorella pyrenoidosa in diabetic rats exposed to cadmium.

OBJECTIVE: The objective of the present study is to evaluate the antihyperlipidemic effect of Chlorella pyrenoidosa in diabetic rats exposed to cadmium (Cd). MATERIALS AND METHODS: Group 1 and 2 rats were treated as control and C. pyrenoidosa control. Group 3 and 4 rats were given single injection of streptozotocin (40 mg/kg b.w; i.p) followed by Cd (0.6 mg/kg b.w; s.c) for 5 days per week for a total period of 90 days. In addition, group 4 rats alone were treated with C. pyrenoidosa throughout the study period of 90 days. Assessments of plasma glucose, insulin, lipid profile and renal function markers were performed in control and experimental rats along with histological examination of kidney tissues. RESULTS: Diabetic rats exposed to Cd showed increased levels of plasma glucose and decreased levels of plasma insulin accompanied by the significantly elevated levels of tissue lipids viz., total cholesterol, triglyceride, free fatty acid, and phospholipids compared with control rats. Alterations in lipoproteins (low density lipoprotein-C, very low density lipoprotein-C, and high density lipoprotein-C) levels were also observed. DISCUSSION: Elevated levels of urinary albumin, creatinine, and blood urea nitrogen confirmed the onset of renal dysfunction in unsupplemented diabetic rats exposed to Cd. CONCLUSION: C. pyrenoidosa (100 mg/kg body weight) supplemented diabetic nephropathic rats showed near normal biochemical profile and well preserved renal histology that substantiate the antihyperglycemic, antihyperlipidemic, and renoprotective effects of C. pyrenoidosa in diabetic rats exposed to Cd.

Colon cancer chemopreventive efficacy of silibinin through perturbation of xenobiotic metabolizing enzymes in experimental rats.

Our findings reported so far demonstrate that silibinin modulates gut microbial enzymes, colonic oxidative stress and Wnt/ß-catenin signaling, to exert its antiproliferative effect against 1,2 di-methylhydrazine (DMH) induced colon carcinogenesis. Since xenobiotic metabolizing enzymes play a crucial role in carcinogen activation and metabolism, we aimed to explore the effect of silibinin on xenobiotic metabolizing enzymes during DMH induced colon carcinogenesis. Male albino rats were randomly divided into six groups. Group 1 served as control and group 2 rats received 50mg/kg body weight of silibinin p.o. every day. Groups 3-6 rats were given DMH at a dose of (20mg/kg body weight subcutaneously) once a week for 15 weeks to induce colonic tumors. In addition to DMH, group 4 (initiation), group 5 (post-initiation) and group 6 (entire period) rats received silibinin (50mg/kg body weight, p.o., everyday) at different time points during the experimental period of 32 weeks. Rats exposed to DMH alone showed increased activities of phase I enzymes (cytochrome b5, cytochrome b5 reductase, cytochromeP450, cytochromeP450 reductase, cytochromP4502E1) and decreased activities of phase II enzymes (Uridine diphospho glucuronyl transferase, Glutathione-S-transferase and DT-Diaphorase) in the liver and colonic mucosa as compared to control rats. Silibinin supplementation modulates the xenobiotic metabolizing enzymes favoring carcinogen detoxification. Evaluation of lipid peroxidation and antioxidants status showed that silibinin supplementation counteracts DMH induced hepatic and circulatory oxidative stress. Tumor burden in experimental animals was assessed both macroscopically and microscopically in the colon tissues. Our findings emphasize the potential chemopreventive action of silibinin against DMH induced colon carcinogenesis.

Oral supplementation of silibinin prevents colon carcinogenesis in a long term preclinical model.

Chemoprevention through dietary intervention is an emerging option to reduce colon cancer mortality. beta-catenin plays an important role in the Wnt signaling cascade that is most commonly dysregulated in colorectal cancer. Our aim was to explore the modulatory effect of silibinin on beta-catenin expression employing 1,2-dimethylhydrazine (DMH) induced colon cancer in male Wistar rats as an experimental model during the different stages of carcinogenesis. Colon tissues were analyzed for the expression of beta-catenin, proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizer regions by using immunohistochemistry and silver staining. Immunoblotting was employed to study cyclin D1 expression. Glutathione (GSH) and glutathione related enzymes were assayed by spectrophotometric analysis. Silibinin inhibited DMH-induced colon cancer by decreasing tumor incidence and multiplicity. Silibinin supplementation to DMH-treated rats restored the levels of GSH-dependent enzymes and decreased the levels of beta-catenin, PCNA, argyrophilic nucleolar organizer regions and cyclin D1. Mechanistically silibinin inhibits DMH-induced colon carcinogenesis by modulating the Wnt/beta-catenin pathway and glutathione redox system. Since colon cancer is highly sensitive to dietary intervention adults who may have preneoplastic lesions in their colon may be benefited by silibinin.

Silibinin ameliorates oxidative stress induced aberrant crypt foci and lipid peroxidation in 1, 2 dimethylhydrazine induced rat colon cancer.

Pharmacological intervention to reduce CRC mortality entails the use of oral agents that can avert carcinogenesis. Silibinin, a major component of silymarin isolated from Silybum marianum (L.) was found to possess attractive remedial features. An in vivo study was designed to elucidate the effect of silibinin on the formation of 1, 2 dimethylhydrazine (DMH) induced aberrant crypt foci (ACF), tissue lipid peroxidation (LPO) and enzymic antioxidants status during different phases of experimental colon cancer. DMH alone treated rats showed significantly (p < 0.05) increased size and number of ACF, accompanied by decreased LPO and enzymic antioxidant activities. Administration of silibinin to DMH treated rats inhibited mean colonic ACF and multi-crypt AC/foci and also improved the levels of enzymic antioxidants in a time dependent manner. Histologically no obvious sign of neoplasia was observed in silibinin supplemented DMH treated rats during the various stages of carcinogenesis. Our results show that silibinin possesses potent chemopreventive activity against colon carcinogenesis.

Silibinin modulates biotransforming microbial enzymes and prevents 1,2-dimethylhydrazine-induced preneoplastic changes in experimental colon cancer.

Chemoprevention directed towards the control of colon carcinogenesis in its early stages should ultimately provide a higher quality of life for people than waiting to treat end-stage disease. Silibinin is a major bioactive compound that is present in the widely consumed dietary supplement Silymarin. The current investigation aimed to explore the effect of the phytochemical silibinin on the suppression of 1,2-dimethylhydrazine-induced colonic preneoplastic changes in a long-term preclinical model. Wistar male rats were divided into six groups: group 1 were control rats, group 2 were control rats that received silibinin alone (50 mg/kg body weight orally everyday), rats in group 3 were injected once weekly with 1,2-dimethylhydrazine (20 mg/kg body weight, subcutaneously 15 times), in addition, group 4 (initiation), group 5 (post initiation) and group 6 (entire period) received silibinin as in group 2. At the end of 32 weeks, the activities of the colonic and faecal biotransforming microbial enzymes were analysed. Modulatory effects were also evaluated using aberrant crypt foci (ACF), dysplastic ACF and tumour incidence as endpoint markers. Silibinin markedly reduced tumour incidence, as compared with the rats treated with unsupplemented 1,2-dimethylhydrazine. The most pronounced inhibition of ACF and dysplastic ACF development was observed in the rats fed with silibinin for the entire period and also during the post initiation period. Silibinin administration also significantly (P<0.05) modulated the biotransforming activity of microbial enzymes. The results of our study suggest that silibinin suppresses 1,2-dimethylhydrazine-induced colon carcinogenesis at various stages and exerts a potential chemopreventive action against colon cancer.