title: Dehydroepiandrosterone sulfate and cytochrome P450 inducers alleviate fatty liver in male rats fed an orotic acid-supplemented diet.
abstract: The effects of the peroxisome proliferator, dehydroepiandrosterone sulfate (DHEAS), and the typical cytochrome P450 (CYP) inducers phenobarbital (PB) and 3-methylcholanthrene (3-MC) on fatty liver were examined in rats. Treating rats with orotic acid caused marked accumulation of lipid droplets in the liver. This effect of orotic acid was almost eradicated by co-treatment with DHEAS and PB. While DHEAS or PB alone also alleviated fatty liver, treatment with 3-MC caused little effect on a reduction in lipid droplets. Histopathological examinations revealed numerous peroxisomes in the liver of rats treated with DHEAS. In addition, a significant increase in the expression on hepatic CYPs was observed in rats the fatty liver of which was attenuated. Regarding other enzymes associated with hepatic fatty acid oxidation, the expression levels of sirtuin 1, sirtuin 6, and carnitine palmitoyltransferase 1 were also upregulated most markedly by treatment with DHEAS alone. Thus, the attenuation in fatty liver observed in the present study is likely due to peroxisome proliferation and the induction of fatty acid-metabolizing enzymes by DHEAS and typical CYP inducers.
authors: Department of Drug Metabolism, Drug Safety Research Center, Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan; Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Kenji
authors: K
authors: Takeuchi
authors: Hirohiko
authors: H
authors: Goto
authors: Yuko
authors: Y
authors: Ito
authors: Makoto
authors: M
authors: Sato
authors: Satoshi
authors: S
authors: Matsumoto
authors: Tadashi
authors: T
authors: Senba
authors: Hideyuki
authors: H
authors: Yamada
authors: Ken
authors: K
authors: Umehara
mesh_terms: D000818:Animals; D065693:Cytochrome P-450 Enzyme Inducers / Q000494:pharmacology / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000139:chemically induced* / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology / Q000627:therapeutic use*; D009963:Orotic Acid / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction / Q000187:drug effects; D020675:Peroxisomes / Q000473:pathology; D010634:Phenobarbital / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: D065693:Cytochrome P-450 Enzyme Inducers; D005227:Fatty Acids; D008748:Methylcholanthrene; D019314:Dehydroepiandrosterone Sulfate; D009963:Orotic Acid; D003577:Cytochrome P-450 Enzyme System; D056564:Sirtuin 1; D010634:Phenobarbital