Effect Of All-trans Retinoic Acid On Liver Retinoids, Oxidative Stress And Hepatic Injury In CBDL Rats

AimTo investigate the effect of all-trans retinoic acid (ATRA) administration on the concentration of retinoids (RA and vitamin A) in liver, oxidative stress and hepatic injury in a rat model of common bile duct ligation (CBDL)-induced liver fibrosis.Methods53 female Wistar rats were randomizedly divided into 5 groups, i.e., sham operation group (group A), CBDL control group (group B) and CBDL with different dose ATRA treatment groups (group C, D, E). Group A consisted of 5 rats .Each of another 4 groups consisted of 12 rats. Liver fibrosis was induced by CBDL for group B, C, D and E rats while sham operation was performed for group A rats. Starting from the third week the rats in group C, D and E respectively received daily administrate of ATRA by gastric feeding at 0.1mg/kg, 1.5mg/kg and 7.5 mg/kg body weight. Animals were sacrificed at the end of the sixth week blood samples were collected from the heart for determination of the serum transaminase and total bilirubin levels. The contents of RA and vitamin A in liver were detected by using HPLC. Glutathione (GSH) level and superoxide dismutase (SOD) activity in liver were determined by a spectrophotometric method. Malondialdehyde (MDA) was determined by the thibsbituric acid method. Liver pathologic changes were observed under the light microscopy and electron microscopy. ResultsCBDL led to the development of liver damage and fibrosis in all CBDL groups. ATRA treatment notably alleviated liver injury such as hepatocellular swelling, steatosis, the swelling of mitochondria and proliferation of smooth endoplasmic reticulum (SER), and partially reduced the formation of fibrosis. Compared with sham-operated group, the levels of RA and vitamin A in liver were significantly decreased by 78% and 72% in the CBDL control group (P<0.01). ATRA at 0.1 mg/kg body weight partially restored RA and vitamin A levels (P<0.05) and ATRA at 1.5 mg/kg and 7.5mg/kg body weight both raised RA and vitamin A concentrations of liver to the same levels of sham-operated rats (P<0.05). The SOD activity and GSH level remarkably decreased while MDA level significantly increased in the CBDL control group as compared with sham-operated rats (P<0.05). Three dosages of ATRA all increased SOD activity and GSH level, reduced MDA Level. ATRA administration at three different dosages remarkably decreased the ALT and AST levels in CBDL rats (P<0.05). ATRA at 1.5mg/kg and 7.5mg/kg decreased ALT, AST levels more significantly than 0.1mg/kg ATRA (P<0.05). ATRA had no effect on the serum TB in CBDL rats.ConlusionATRA treatment could ameliorate liver injury through increasing GSH levels and SOD activity and decreasing MDA level via the restoration of restoring RA and vitamin A contents in liver in CBDL rats.