title: Silibinin alleviates N-nitrosodimethylamine-induced glutathione dysregulation and hepatotoxicity in rats.
abstract: The present study was designed to evaluate the hepatoprotective and antioxidant potentials of silibinin (SBN) against N-nitrosodimethylamine (DMN)-induced toxic insults in the rat liver. The liver damage was induced in Wistar albino rats by repeated administration of DMN (10 mg·kg(-1) b.w., i.p.) on 3 consecutive days per week for 3 weeks. SBN (100 mg·kg(-1) b.w., p.o.) was given daily to the DMN treated rats for two weeks. The marker enzymes of liver toxicity and second-line enzymic and non-enzymic antioxidants were evaluated in serum and liver tissues before and after SBN treatment. Histopathology of the liver was evaluated by H & E staining. The DMN treatment produced a progressive increase in all the serum marker enzymes (AST, ALT, ALP, LDH, and γ-GT), peaking on Day 21. This treatment produced highly significant decreases in all the second-line antioxidant parameters (GSH, GST, GR, GPx, and vitamins C and E). The SBN treatment significantly reversed the DMN-induced damages, towards normalcy. Histopathological studies confirmed the development of liver toxicity in DMN-treated rats, which was reversed by SBN treatment in corroboration with the aforementioned biochemical results, indicating the hepatoprotective and antioxidant properties of SBN. In conclusion, the DMN-induced degenerative changes in the liver were alleviated by SBN treatment and this protective ability may be attributed to its antioxidant, free radical scavenging, and membrane stabilizing properties.
authors: Food and Hepatotoxicology Laboratory, Department of Pharmacology and Environmental Toxicology, University of Madras, Taramani, Chennai 600113, India.
authors: Devaraj
authors: D
authors: Ezhilarasan
authors: Food and Hepatotoxicology Laboratory, Department of Pharmacology and Environmental Toxicology, University of Madras, Taramani, Chennai 600113, India. Electronic address: hepatotoxicology.lab@gmail.com.
authors: Sivanesan
authors: S
authors: Karthikeyan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D004128:Dimethylnitrosamine / Q000633:toxicity*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D008297:Male; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D020011:Protective Agents; D012838:Silymarin; D000077385:Silybin; D005978:Glutathione; D004128:Dimethylnitrosamine
keywords: Dimethylnitrosamine; Glutathione dysregulation; Hepatotoxicity; Oxidative stress; Silibinin