An acute increase in systemic bile acid levels in rats treated with tunicamycin

We investigated whether an endoplasmic reticulum (ER) stress-inducing chemical tunicamycin (TM) modulates bile acid (BA) metabolism in rats. Male Wistar rats were intraperitoneally administered TM at 0.1 mg/kg body weight or vehicle, and samples were collected 2 days post-treatment. TM administration induced the levels of hepatic ER stress-related proteins. Increases were observed in both 12-hydroxylated and non-12-hydroxylated BA concentrations in the aortic plasma of the rats with TM treatment. Hepatic expression of Abcc3 that encodes BA transporter was significantly upregulated and positively correlated with the aortic BA levels. While these responses may not be exclusively attributable to ER stress and could partially arise from ER stress-independent effects of TM, these findings offer fundamental insights into BA metabolism in response to exogenous chemicals and suggest that ER stress contributes to increased systemic BA circulation when hepatic function is compromised.