Effect of pirfenidone on renal tubulointerstitial fibrosis

Effect of pirfenidone on renal tubulointerstitial fibrosis

Abstract

Renal tubulointerstitial fibrosis (TIF) is the common end stage of various chronic renal diseases, and pirfenidone (PFD) is a novel, broad-spectrum anti-fibrotic compound but little is known about its effect and mechanism of action on renal TIF. In this work, we employed a unilateral ureteral obstruction (UUO) rat model to investigate the apoptosis of renal tubular epithelial cells (RTC) after PFD treatment. Thirty-five Sprague Dawley (SD) rats were randomized into three groups: sham-operated group (n=7), UUO group (n=14) and PFD group (n=14). All rats were sacrificed at day 7 or 14 after operation. Renal histology was studied by using periodic acid schiff reagent (PAS) and Masson trichromic stain (MASSON); apoptosis was detected by in situ terminal deoxynucleotide transferase-mediated dUTP-biotin nick end-labeling (TUNEL); tubular caspase-3 expression was assessed by immunohistochemistry. The content of malondialdehyde (MDA) and total activity of superoxide dismutase (T-SOD) in the renal cortex was determined by chemical colorimetry method. TIF, apoptosis of RTC, tubular expression of caspase-3 and the content of MDA were increased in the UUO group compared with those in the sham-operated group, and were ameliorated significantly by PFD treatment (P<0.05). The activity of SOD was decreased in the UUO group, but was improved by PFD treatment (P<0.05). Our results showed that PFD could ameliorate TIF in the UUO group, and the possible mechanism was by reducing the apoptosis of RTC, which involved oxidative stress and caspase-3.

Keywords

pirfenidone / apoptosis / caspase 3 / oxidative stress