Psoralen induces liver injury and affects hepatic bile acids metabolism in female and male C57BL/6J mice

Abstract

Psoralen is a major component of Fructus Psoraleae that could induce liver injury. In this study, C57BL/6J mice were administered with psoralen at doses of 80 mg/kg for 3, 7 and 14 days. Blood and liver samples were collected for serum biochemistry and histopathology examinations, respectively. Psoralen led to liver injury with significantly increased liver weight and liver coefficient and up regulated serum ALT, AST and TG but down regulated serum TC and TP. The expression of bile acid-associated transporters and enzymes was detected by western blot, and the results showed that psoralen significantly down-regulates the expressions of CYP7A1, CYP27A1, BSEP and OSTα protein while up-regulates the expressions of HMGCR and FASN, resulting in the obstacles of bile acid efflux in the liver. The contents of 24 kinds of bile acids in the liver were measured by LC-MS/MS, and the results showed that psoralen led to the accumulation of unconjugated bile acids in the liver, such as ALCA and CA, which were more severe in male mice than female mice. It was indicated that psoralen may disrupt the balance of bile acid metabolism by inhibiting the expression of the efflux transporter, which then leads to liver damage.

Identifying Crude Drugs in Kampo Medicines Associated with Drug-Induced Liver Injury Using the Japanese Adverse Drug Event Report Database: A Comprehensive Survey

“…Despite conducting a literature survey on Glehnia Root and Rhizome, we found no information on the related hepatotoxicity. However, when we focused on the coumarin components (imperatorin, psoralen, and bergapten) contained in Glehnia Root and Rhizome, basic studies indicated the hepatotoxicity of psoralen [ 16 , 17 , 18 ]. The present results may reflect that DILI is caused by psoralen.…”