4-phenyl butyric acid improves hepatic ischemia/reperfusion and affects gene expression of ABC transporter Abcc5 in rats.

Abstract

Aim: To assess the effects of 4-phenyl butyric acid (PBA) on oxidative stress, inflammation, liver histology, endoplasmic (ER) reticulum stress, and the expression levels of ATP-binding cassette transporter family members in a hepatic ischemia-reperfusion (IR) model.

Methods: Thirty-five rats were randomly divided into five groups: sham, IR, IR + 100 mg kg-1 PBA, IR + 200 mg kg-1 PBA, and IR + placebo. After sacrifice, we assessed serum biochemical variables, myeloperoxidase (MPO), malondialdehyde (MDA), total antioxidant status (TAS), and total oxidant status (TOS). The expression levels of Abcc (2 and 5), Abcg2, Abcf2, Ire1-α, and Perk genes were measured with a quantitative real-time polymerase chain reaction.

Results: Serum biochemical variables, MPO, MDA, TAS, and TOS levels of the PBA groups (especially in the low dose group) were lower than in the IR and placebo group (P<0.05). Histological tissue damage in the IR group was more severe than in the PBA groups. Ire1-α and Perk expression levels were significantly lower in the PBA groups than the IR group (P<0.001). Abcc (2 and 5) and Abcg2 expression levels were significantly lower in the IR group than in the sham and PBA groups (P<0.001, P<0.035, and P<0.009, respectively).

Conclusions: The use of PBA significantly positively affected IR injury, which makes PBA a candidate treatment to reduce liver IR.