Therapeutic effect and mechanism of 4‑phenyl butyric acid on renal ischemia‑reperfusion injury in mice

Abstract

The aim of the present study was to explore the effects and possible mechanism of 4-phenylbutyric acid (4-PBA) on renal ischemia-reperfusion injury (RIRI) in mice. A RIRI model of HK-2 cells was constructed using hypoxia/reoxygenation (H/R) treatment. Dexmedetomidine and 4-PBA were used to treat the cells before and after modeling. Apoptosis and expression levels of cyclophilin D (CypD), cytochrome c, eukaryotic translation initiation factor 2alpha (eIF2alpha), glucose-regulated protein 78 (GRP78), intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 were measured using flow cytometry, western blot- ting and immunohistochemistry. The renal volume, weight and renal arterial resistance index (RRI) were determined using the renal ischemia model. Compared with untreated model cells, 4-PBA treatment significantly decreased apoptosis and the expression levels of CypD, Cytochrome c, eIF2alpha and GRP78 in HK-2 cells. There was no significant change in renal volume and weight after modeling, but RRI was significantly decreased after 4-PBA treatments in the model. Western blot- ting and immunohistochemistry analysis demonstrated that 4-PBA treatment also significantly decreased the expression of ICAM-1 and VCAM-1. Overall, 4-PBA had a therapeutic effect on RIRI in mice. This protection may be mediated by decreasing the expression levels of CypD, Cytochrome c, eIF2alpha and GRP78, and subsequent reduction of cellular oxygen free radicals and apoptosis, leading to an alleviated endoplasmic reticulum stress response and RIRI.Copyright © 2022 Spandidos Publications. All rights reserved.