Protective effects of Mg-CUD against D-galactosamine-induced hepatotoxicity in rats

This study examined the protective effects of magnesium chenoursodeoxycholic acid (Mg-CUD), a magnesium trihydrate salt of chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), against D-galactosamine (D-GaIN)-induced liver injury. Hepatotoxicity was induced by intraperitoneal injection of D-GaIN (700 mg/kg) and Mg-CUD (15.625, 31.25 and 62.5 mg/kg) was administered orally once a day for 2 weeks and 6 h after D-GaIN injection. Significant increases in the level of serum alanine aminotransferase activity and lipid peroxidation were attenuated by Mg-CUD 24 h after D-GaIN treatment. Hepatic glutathione/oxidized glutathione ratio was decreased, and this decrease was attenuated by Mg-CUD. Mg-CUD attenuated the increase in the levels of serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, while it augmented the increase in serum IL-10 level and heme oxygenase (HO)-1 protein expression. Mg-CUD attenuated increased levels of TNF-alpha, IL-6, and IL-1 beta mRNA expression. Increased levels of IL-10 and HO-1 mRNA expression were augmented by Mg-CUD. The increased nuclear level of nuclear factor-kappa B (NF-kappa B) and decreased cytosolic level of Inhibitory kappa B-alpha protein were attenuated by Mg-CUD. Nuclear phosphorylated c-Jun (p-c-Jun) level showed a significant increase and this increase was attenuated by Mg-CUD. Our results suggest that Mg-CUD ameliorates D-GaIN-induced acute hepatitis and that this protection is likely due to its anti-oxidative and anti-inflammatory activities, and inhibition of NF-kappa B nuclear translocation and nuclear p-c-Jun expression. (C) 2011 Elsevier B.V. All rights reserved.