HEPATOPROTECTIVE EFFECT OF PROPAGERMANIUM ON CORYNEBACTERIUM-PARVUM AND LIPOPOLYSACCHARIDE-INDUCED LIVER-INJURY IN MICE

Propagermanium is an organic germanium compound with immunopotentiatin g activity. We examined the hepatoprotective effect of propagermanium and its mechanism in an experimental animal model of acute Liver injur y induced with Corynebacterium parvum (C. parvum) and lipopolysacchari de (LPS) injection. Oral pretreatment with propagermanium decreased al anine aminotransferase (ALT) and aspartate aminotransferase (AST) acti vity in a dose-dependent manner. Significant attenuation of ALT and AS T activity was obtained at a dose of 3 mg/kg. Administration of propag ermanium also inhibited the infiltration of mononuclear cells into the liver of mice induced by C. parvum/LPS. Immunohistochemical examinati on revealed infiltration of the liver by CD4-, CD8-, CD11b- and Gr-1-p ositive cells. Propagermanium prevented CD4- and CD11b-positive cells from infiltrating the liver. In this animal model, blood cytokine leve ls increased rapidly after LPS injection, causing severe hepatitis. No tably, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma ( IFN-gamma) are important mediators of the progress of liver injury. We demonstrated that propagermanium reduced IFN-gamma production by 53% at a dose of 3 mg/kg and also significantly inhibited the production o f interleukin-12 (IL-12). These results indicate that propagermanium i nhibits cell infiltration in the liver and cytokine production, and im proves massive liver injury in C. parvum/LPS mice.