Psoralen induces liver injuries through endoplasmic reticulum stress signaling in female mice.

ABSTRACT

Psoralen is the main coumarin component of Fructus psoraleae. Previously, we have found that psoralen induced hepatocytes apoptosis via PERK and ATF6 related ER stress pathways in vitro. In this study, we investigated the toxicity and ER stress induced by psoralen in female C57 mice. Mice were fed with 80 mg/kg of psoralen intra-gastrically for either 3, 7, or 21 days. Liver and kidney were weighed and their coefficients were calculated. The serum was isolated to examine the biochemical parameters including alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, alkaline phosphatase (ALP) activity, blood urea nitrogen (BUN), total bile acid (TBA), total bilirubin (TBIL), and creatinine (CRE). The transcription and expression of ER stress-related markers were determined by Wes-automated Protein Simple system, Western blot and RT-PCR. Psoralen administration for 3 days significantly increased liver coefficients but decreased kidney coefficients of mice. Histopathological examination showed minimal inflammatory cell foci and vacuolar degeneration in the liver. Besides, serum levels of ALT, TBA, BUN, and CRE were markedly altered by psoralen. Moreover, psoralen significantly increased expression and transcription levels of ER stress related markers, including Grp78, PERK, eIF2α, ATF4, IRE1α, ATF6, and XBP1. These results illustrated that psoralen induced liver injuries through ER stress signaling in female mice.