The combination of
rifampin and
pyrazinamide is commonly used in the clinical treatment of
tuberculosis, but its safety needs to be further clarified. Mice were intragastric administration of
rifampin 300 mg/kg,
pyrazinamide 625 mg/kg,
rifampin 300 mg/kg plus
pyrazinamide 625 mg/kg. The results showed that
rifampin significantly increased
transaminases, TBIL and TBA levels in serum, increased TG, TC content, HMGCR and CYP7A1
protein, CYP7A1, FGFR4, PXR, FAS and FXR
mRNA expression, but decreased the level of
SREBP-1c mRNA and induced severe
steatohepatitis and hepatocyte
necrosis in liver in mice. While
pyrazinamide can improve many abnormal indexes when it used with RFP, including liver histopathology, liver TG, TC level and serum biochemistry, GPHBP1, FAS and CYP7A1
mRNA, LPL
protein expression and activity induced by
rifampin. However,
pyrazinamide alone significantly decreased liver TG levels and caused only slight inflammatory pathological changes in liver histopathology in mice. These data suggested that
rifampin increases TG and TC levels in the liver may be related to activate HMGCR, CYP7A1, PXR and FXR, theses
toxic actions of
rifampin were alleviated by
pyrazinamide may be due to inhibite the activity of CYP7A1, PXR and FAS, and increasing the LPL
protein expression and activity.