Gene expression on liver toxicity induced by administration of haloperidol in rats with severe fatty liver

Sudden deaths are often encountered in schizophrenic patients prescribed with antipsychotic drugs, and fatty liver may be more prevalent among patients with schizophrenia. The aim of this study is to investigate the adverse effects of antipsychotic drugs on fatty liver. We administered haloperidol intraperitoneally to fatty liver rats and examined the mRNA expression in the liver. Basic expressions of cytochrome P450 (CYP)1A2, CYP2C11 and CYP3A2 decreased, and response of these CYPs to haloperidol was reduced in the fatty liver. Metabolism of haloperidol was also suppressed in the fatty liver rats. Moreover, hepatic injury by administration of haloperidol was shown pathohistologically and molecular-biologically in severe fatty liver. These results suggest that fatty liver increases susceptibility to adverse effects of haloperidol, possibly leading to life-threatening events. It should be noted by clinicians that excessive dose of antipsychotic drugs may be more harmful in patients with fatty liver.