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.
Hanagama
Masakazu
M
Department of Forensic Medicine and Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City, Mie 514-8507, Japan.
Inoue
Hiromasa
H
Kamiya
Munechika
M
Shinone
Kotaro
K
Nata
Masayuki
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood / Q000633:toxicity*; D017209:Apoptosis; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; D003580:Cytochromes / Q000235:genetics / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism*; D049429:Forensic Pathology; D053593:Forensic Toxicology; D006220:Haloperidol / Q000097:blood / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D039181:Steroid 16-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
D014150:Antipsychotic Agents; C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D003580:Cytochromes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; C017170:Cyp1a2 protein, rat; C465260:Cyp3a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006220:Haloperidol