Low-dose ATRA Supplementation Abolishes PRM Formation In Rat Liver And Ameliorates Ethanol-induced Liver Injury

AimTo investigate the effects of low dose all-trans-retinoic acid (ATRA) supplementation on hepatic retinoids concentrations, formation of polar retinoid metabolites (PRMs) and liver injury in the ethanol-fed rats .MethodsThe rat model of alcoholic liver disease (ALD) was induced by intragastric infusion of ethanol: 30 male SD rats were randomly assigned to four groups, group A was a control group, rats of group B, C, and D were received intra-gastric infusion of alcohol (8 g/kg) for 8 weeks, and then rats of group C and D were adminstrated all-trans-RA in two different doses (150 ug/kg body wt and 1.5 mg/kg body wt) by intragastric infusion for 4 weeks. The concentrations of retinoids in rat liver and plasma were detected with HPLC; the pathological changes of liver were observed by light microscopy and electron microscopy; the serum transaminases concentration were determined by a semi-automatic biochemical analysator. ResultsRetinoids (vitamin A, RA, retinyl palmitate) concentrations in liver and RA concentration in plasma in ethanol-fed rats were markedly diminished (p<0.01) after ethanol feeding for 12 weeks. Furthermore, obvious peaks of PRMs were formed in livers of ethanol-fed rats. ATRA of 150 ug/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 1.5mg/kg supplementation completely restored RA concentration in liver and plasma, and retinyl palmitate concentration 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 reduced hepatocellular swelling, steatosis, the swelling of mitochondria and proliferation of smooth endoplasmic reticulum (SER). ATRA treatment obviously decreased levels of serum transaminases in ethanol-fed rats (P<0.05).ConclusionLow-dose ATRA treatment can restore the retinoids concentrations and abolish PRMs formation in liver of ALD rats, and eventually ameliorates liver injury.