in vivo protective effects of silymarin on DMN-induced hepatotoxicity in rats

ABSTRACT

Dimethyl nitrosamine [DMN] is a very potent chemical carcinogen which occurs naturally in the environment and in a wide variety of food stuffs, and can be formed in the body by nitrosation of secondary or tertiary amines in the presence of nitrite, nitrate or nitrogen oxides. Silymarin is a powerful antioxidant and has a potent free radical scavenging activity, said to protect cells of liver, brain and other cells in the body from toxins. To examine the in vivo protective effects of silymarin on the induced oxidative damage in livers of DMN-intoxicated rats histologically and immunohistochemically. The ability of silymarin to protect and detoxify DMN toxicity was examined in rat livers. Dietary pretreatment of rats [body weight 125-135 g] with silymarin [0.9 mg/g body weight] for two weeks prior to the intraperitoneal injection of DMN, reversed the hepatotoxic effects of DMN, as examined histologically. DMN in two doses of 15 micro g/kg or 25 micro g/kg was injected. After DMN treatment, the animals were fed with diet with silymarin or without for 48 hours. Rats were sacrificed 48 hours after DMN injection. The immunoreactivity of cells of rats' livers was examined for antibodies of heat shock protein 70 [HSP70] [HSPs are a family of proteins that are triggered to be induced when a cell undergoes environmental stresses including oxidative stress, pathogenic conditions ...etc]. The histological evaluation revealed prominent changes in groups received DMN in high dose more than low dose. Treatment with silymarin reversed this effect. The immunohistochemical assay for the stress-protective proteins "HSP70" showed that treatment with silymarin triggered more expression of this protein. Silymarin can provide substantial protective effect against DMN-induced hepatic oxidative damage with therapeutic potential to be used in human