The combination of lipopolysaccharide and D-galactosamine administration show positive genotoxic effect in mice liver

Abstract

AbstractLipopolysaccharide (LPS)/D-galactosamine (D-GalN) co-administration induced acute liver injury (ALI) and hepatic fibrosis have been extensively studied. However, whether LPS/D-GalN show genotoxic effect is current unknown. Male mice were divided into eight groups and each group contain eight animals. For the acute administration of LPS/D-GalN, the mice were given a single intraperitoneal (i.p.) injection of LPS/D-GalN (25 μg/kg + 250 mg/kg, 25 μg/kg + 500 mg/kg, 50 μg/kg + 500 mg/kg body weight) for 6 h, respectively. The chronic administration was conduct by the i.p. injection of LPS/D-GalN (10 μg/kg + 100 mg/kg) every other day for 8 weeks. Saline solution (0.9%) and cyclophosphamide (CTX) (50 mg/kg body weight) injection were used as negative and positive control, respectively. Using single cell gel electrophoresis (SCGE) assay, we found that the acute administration of LPS/D-GalN induces severe DNA damage in mice hepatic cells, but not in brain, sperm and bone marrow cells, implied the genotoxicity of LPS/D-GalN. Interestingly, the chronic treatment of LPS/D-GalN causes significant genotoxic effect in both hepatic and brain cells, but not sperm and bone marrow cells. Histopathological examination in liver and brain section consistent with SCGE results, accordingly. Our study, for the first time, reported the genotoxic potential of LPS/D-GalN co-administration. In addition, LPS/D-GalN administration may serve as an experimental model for further genotoxic study.