| Objective To investigate the protective action of ethyl pyruvate on liver injury induced by rifampicin in mice and its possible mechanism. Methods Twenty-four male C57BL/6 mice were randomly divided into normal group, model group (rifampicin, 200 mg·kg-1·d-1) and ethyl pyruvate group (rifampicin, 200 mg·kg-1·d-1 + ethyl pyruvate, 40 mg·kg-1·d-1). Each group consisted of eight animals. The mice were sacrificed on day 7. The serum levels of alanine aminotransferase (ALT), total bilirubin (TBIL), direct bilirubin (DBIL) and alkaline phosphatase (ALP) were measured. The histopathological changes of liver tissues were observed. The liver tissue was dissected for measuring TBA, MDA, SOD and acetylated- high mobility group box-1. The expression of high mobility group box-1 in liver was detected by immunohistochemistry. Results Compared with normal group, the serum levels of TBIL, DBIL, ALP and ALT in model group significantly increased (P<0.05). Obvious vacuolar degeneration and fatty changes of hepatocyte and eosinophi changes, nucleus dissolution and condensation of a few hepatocyte in mice of model group were observed. The expressions of HMGB1 and AC-HMGB1 were elevated (P<0.05), and HMGB1 was mostly located in hepatocyte cytoplasm. Compared with model group, the serum levels of TBIL, DBIL, ALP and ALT were significantly reduced in EP group (P<0.05). The changes in liver pathology were greatly relieved. The levels of TBA and MDA in liver tissue were also significantly reduced (P <0.05), but the level of SOD was significantly elevated (P <0.05). The expressions of HMGB1 and AC-HMGB1 were also reduced (P<0.05), and HMGB1 was mostly located in hepatocyte nucleus. Conclusion Rifampicin may cause severe hepatic damage, and EP could reduce the degree of liver injury. The mechanism may be that EP not only has antioxidant activity, but also can down-regulate the expression of HMGB1 and AC-HMGB1 in liver tissue and regulate the distribution of HMGB1. |
