Effects and mechanisms of rifampin on hepatotoxicity of acetaminophen in mice

► Rifampin possess the species-specific protection against the liver injury induced by acetaminophen in mice. ► Rifampin enhanced the biotransformation of acetaminophen to p-aminophenol. ► Rifampin reduced glutathione depletion in vivo and in vitro. ► Microsomal drug-metabolizing enzyme and glutathione reductase activity was increased by treatment with rifampin. ► Microsomal Ca2+-ATPase activity was not directly related to acetaminophen toxic metabolites in vitro.