Protective Effects And Possible Mechanisms Of Dehydrocavidine On Carbon Tetrachloride-induced Hepatoxicity In Rats

Objective:The protective effects of dehydrocavidine(DC),a main active ingredient of Corydalis Saxicola Bunting totle alkaloid,on carbon tetrachloride(CCl₄) induced hepatotoxicity and the possible mechanisms involved in this protection were investigated in male Sprague-Dawley rats.Methods:CCl₄ was used to induce various liver injuries.In acute hepatoxicity studies, pre-treated rats were given DC 48,24 and 2 h prior to CCl₄ administration,however,in post-treatment groups,rats were treated with DC at 2,24 and 48 h after CCl₄ intoxication. Hepatic fibrosis was induced by 12-week CCl₄ intoxication in rats,and DC was then given 3 times a week from the 5^th to 12^th week.Following DC treatment,blood was collected from the rat abdominal aorta under sodium pentobarbital anesthesia and serum enzymatic activities of alanine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase (LDH),alkaline phosphatase(ALP) and total bilirubin(TBIL) were detected.Hepatic antioxidant enzymes glutathione peroxidase(GPX),superoxide dismutase(SOD),and malondialdehyde(MDA) were investigated.After the final treatment,hepatic fibrosis rats were placed in metabolic cages to collect overnight urine.Hydroxyproline(HYP) analysis and specific stain of Sirius red were investigated in hepatic fibrosis liver;moreover,Oligo Microarray Analysis and quantitative real-time reverse-transcription polymerase chain reaction(qRT-PCR) verification were carried out.Results:The elevated levels of ALT,AST and oxidative stress induced by CCl₄ were dose-dependently decreased by DC in both acute hepatictoxicity protection and hepatic fibrosis curative experiments.H&E pathological scores of the liver slices were degraded by DC adenninistration in acute liver injury and hepatic fibrosis rats,which were compared to model ones.Hepatic level of HYP and pathological score of Sirius red stain were also significantly attenuated by DC treatment in hepatic fibrosis rats.Furthermore,hepatic fibrogenesis genes,such as IL18,BcL2,Rad50,Cyp3a13,and et al.,were extensively regulated by DC.Conclusion:DC may degrade oxidative stress level in CCl₄ induced acute hepatotoxicity rats,which indicates the preventive and curative effects of DC on acute liver injuries. Moreover,in CCl₄ induced liver fibrosis rats,DC could significantly ameliorate oxidative stress level and regulate hepatic fibrogenesis related genes,which correlate with their protective effects on hepatic fibrosis.