title: Low-dose ATRA supplementation abolishes PRM formation in rat liver and ameliorates ethanol-induced liver injury.
abstract: The effects of all-trans-retinoic acid (ATRA) in low doses supplementation on concentrations of polar retinoid metabolites (PRM) and retinoids in the ethanol-fed rat liver, and on hepatocyte injury were investigated. The rat model of alcoholic liver disease (ALD) was induced by intragastric infusion of ethanol, and then the rats were administrated with ATRA in two different doses (150 microg/kg body weight and 1.5 mg/kg body weight) for 4 weeks. Concentrations of retinoids in rat liver and plasma were determined by using HPLC. Liver tissues pathologic changes were observed under the light microscopy and electron microscopy. The serum transaminases concentrations were measured. The results showed that the HPLC analysis of retinoids revealed that retinoids (vitamin A, RA, retinyl palmitate) concentrations in ethanol-fed rat liver and RA concentration in ethanol-fed rat plasma were markedly diminished (P<0.01) after ethanol feeding for 12 weeks. Furthermore, obvious peaks of PRM were formed in livers of ethanol-fed rats. ATRA 150 microg/kg supplementation in ethanol-fed rats for 4 weeks raised RA concentration in both liver and plasma, and also raised vitamin A concentration in liver to control levels, partially restored retinyl palmitate concentration (P<0.05) in liver. ATRA 1.5 mg/kg supplementation raised not only RA concentrations in liver and plasma but also retinyl palmitate concentrations in liver. However, the vitamin A concentration in liver of ATRA-supplemented rats (1.5 mg/kg) was higher than that of controls (P<0.05). The histologic observation of liver tissues indicated that ATRA treatment notably alleviated hepatocellular swelling, steatosis, the swelling of mitochondria and proliferation of smooth endoplasmic reticulum (SER). ATRA treatment greatly decreased levels of serum transaminases as compared with the only ethanol-fed group (P<0.05). It was concluded that low-dose ATRA treatment could restore retinoids concentrations and abolish the PRM formation in liver of ALD rats, and then ameliorate the injury of liver cells.
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Pan
authors.forename: Zili
authors.initials: Z
authors.lastname: Dan
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.forename: Wangxian
authors.initials: W
authors.lastname: Tang
authors.forename: Jusheng
authors.initials: J
authors.lastname: Lin
mesh_terms: D000818:Animals; D000431:Ethanol; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy*; D008297:Male; D051381:Rats; D012176:Retinoids / Q000378:metabolism*; D014212:Tretinoin / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D012176:Retinoids; D000431:Ethanol; D014212:Tretinoin