title: Acute exposure of apigenin induces hepatotoxicity in Swiss mice.
abstract: Apigenin, a dietary flavonoid, is reported to have several therapeutic effects in different diseases including cancer. Toxicity of Apigenin is however, least explored, and reports are scanty in literature. This warrants dose-specific evaluation of toxicity in vivo. In the present study, Apigenin was administered intraperitoneally to Swiss mice at doses of 25, 50, 100 and 200 mg/kg. Serum levels of alanine amino transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase (ALP) were measured along with the examination of liver histology, reactive oxygen species (ROS) in blood, lipid peroxidation (LPO), glutathione level, superoxide dismutase activity, catalase activity, glutathione S-transferase activity and gene expression in liver tissue. Increase in ALT, AST, ALP, ROS, ratio of oxidized to reduced glutathione (GSSG/GSH) and LPO, altered enzyme activities along with damaged histoarchitecture in the liver of 100 or 200 mg/kg Apigenin treated animals were found. Microarray analysis revealed the differential expression of genes that correspond to different biologically relevant pathways including oxidative stress and apoptosis. In conclusion, these results suggested the oxidative stress induced liver damage which may be due to the regulation of multiple genes by Apigenin at higher doses in Swiss mice.
authors.affiliation: Division of Toxicology, Central Drug Research Institute (CSIR), Lucknow, India.
authors.forename: Prabhat
authors.initials: P
authors.lastname: Singh
authors.forename: Shrawan Kumar
authors.initials: SK
authors.lastname: Mishra
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Noel
authors.forename: Sharad
authors.initials: S
authors.lastname: Sharma
authors.forename: Srikanta Kumar
authors.initials: SK
authors.lastname: Rath
mesh_terms: D000818:Animals; D047310:Apigenin / Q000633:toxicity*; D017209:Apoptosis / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000097:blood; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000097:blood
chemical_list: D004798:Enzymes; D017382:Reactive Oxygen Species; D047310:Apigenin