YULANGSAN Polysaccharide Protective Effect Of Rifampicin, Isoniazid And Pyrazinamide-induced Drug-induced Liver Injury

Objective: This study evaluates the hepatoprotective effect of Yulangsanpolysaccharide (YLSPS) against isoniazid (INH)-, rifampicin (RIF)-andpyrazinamide (PZA)-induced hepatic injury in mice.Method: The hepatic injury model in mice was produced by intragastricadministration with pyrazinamide (50,100,200mg.kg-1) and combinedrifampicin, isoniazid and pyrazinamide (25+25+25,50+50+50,100+100+100mg.kg-1) for once daily. The mice were sacrificed on7th day,10th day and15thday respectively. The liver index and activity of AST and ALT in serum weredetected. The mice were randomly divided into six groups:(1) the control group;(2) the model group;(3) the positive group;(4) the YLSPSHgroup;(5) theYLSPSMgroup; and (6) the YLSPSLgroup. Aside from the normal group, theother groups were gavaged with PZA (200mg.kg-1) and INH+RIF+PZA(100+100+100mg.kg-1). Two hours later, the model group received distilledwater; the positive group,200mg/kg bifendate; the YLSPSHgroup,400mg/kg YLSPS; the YLSPSMgroup,200mg/kg YLSPS; and the YLSPSLgroup,100mg/kg YLSPS for15d.Result: The combined administration of INH, RIF and PZA resulted inelevation of the serum hepatic enzymes (AST and ALT), malondialdehyde(MDA) and nitric oxide (NO) levels. And combination used also decreased theglutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase(GSH-PX) contents. However, after treatment with YLSPS, the activities ofAST and ALT were decreased, and MDA and NO levels were found to bereduced. YLSPS was able to increase SOD, GSH and GSH-PX in the livertissue while reducing tissue degeneration and necrosis.Conclusion: From these results, it can be concluded that YLSPS is beneficialagainst anti-tubercular drug-induced hepatic injury (ADIH). Objective: To study the hepatoprotective effect of Yulangsan polysaccharide(YLSPS) against rifampicin (RFP)-, isoniazid (INH-) and pyrazinamide(PZA)-induced hepatocytes injury.Method: The human Chang liver cells and LO2liver cells were cultured, thecells were damaged using different concentration of anti-TB drugs like RFP,INH and PZA. Then, MTT assay was used to test the survival rate of damagedhepatocytes induced by anti-TB drug.The concentration of drug in whichsurvival rate among80%-85%represented the optimum concentration forbuilding liver cell damage model. The damaged hepatocytes were treated withYLSPS. After treated with YLSPS, the activities of alanine aminotransferase(ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) inthe culture supernatants, and the contents of malondialdehyde (MDA) andsuperoxide dismutase (SOD) in hepatocytes were determined to access thehepatoprotective effect of YLSPS in anti-TB induced liver cell injury.Result: Compared with model group, YLSPS could significantly decrease thelevel of AST, ALT and LDH in supernatants and the content of MDA in hepatocytes and also increased the contents of SOD in hepatocytes.Conclusion: YLSPS is beneficial against anti-tubercular drug-inducedhepatocytes injury, the mechanism may be associated with its antioxidant andscavenging free radicals effects.