Effects of silymarin on hepatic DNA damage and expression of related cytokines in Cyprinus carpio var.jian

The present study aimed to evaluate the hepatoprotective effects of silymarin against carbon tetrachloride(CCl₄)-induced hepatotoxicity in Cyprinus carpio var.jian.Fish were fed diets containing four doses of silymarin(0,0.1,0.5,and 1.0 g/kg)for 60 d,and then given an intraperitoneal injection of 30% CCl₄ in olive oil at a volume of 0.05 mL/10 g body weight.At 72 h post injection,liver samples were collected for the liver index,comet assay,histopathological examination and cytokines mRNA detection.Results showed that the increase of the liver index induced by CCl₄ was significantly inhibited by pre-treating the fish with 0.5 and 1.0 g/kg silymarin in the diets.Comet assay showed silymarin could effectively reduce DNA fragment generation of hepatic cells;tail moment,olive tail moment,tail length and tail DNA% were positively changed in fish pretreated with 0.5 and 1.0 g/kg silymarin.In the liver tissue,silymarin had a protective effect on Jian carps with the alleviation of histological changes such as cell swelling,extensive vacuoles degeneration,karyopyknosis and karyolysis.At the same time,the elevation of nuclear factor-κB(NF-κB/C-Rel)and iNOS mRNA expressions induced by CCl₄ were also inhibited by the pre-treatments with 0.5 and 1.0 g/kg silymarin,and the IL-1β mRNA expression was significantly inhibited by pre-treatment with 0.1,0.5 and 1.0 g/kg slymarin.The positive effects of silymarin on the liver index,comet assay,histopathological examination and gene expressions were observed in a dose-dependent manner.Overall results prove that silymarin can improve the degree of hepatic cell DNA damage,and the hepatoprotective functions may be related to inhibition of the NF-κB activation and down-regulation of the downstream genes expression such as iNOS and IL-1β.