The potential reno-protective effect of pirfenidone against renal ischemia/reperfusion injury in a mouse model

Abstract

Objective: This study aimed to assess whether pirfenidone offers protection to the kidneys in a mouse model subjected to renal ischemia-reperfusion injury, focusing particularly on its anti-inflammatory and anti-apoptotic effects. 

Methods: Twenty-eight adult male mice were randomly divided into four groups of seven: Sham, Ischemia, Vehicle (DMSO), and Pirfenidone. We induced bilateral renal ischemia for 30 minutes, followed by 2 hours of reperfusion. Pirfenidone at a dose of 300 mg/kg or the vehicle was administered orally 30 minutes before ischemia. After reperfusion, serum and kidney tissues were collected to analyse markers of renal function, urea and creatinine, along with indicators of kidney damage (KIM-1), inflammation (IL-6), and apoptosis (caspase-3). Histological examination was also performed to evaluate tubular injury.

Results: The ischemia and vehicle groups showed considerably higher levels of serum creatinine, urea, and KIM-1, and increased levels of IL-6 and caspase-3 in kidney tissues, compared to the sham group (P<0.001). Treatment with pirfenidone resulted in decreased biochemical parameters when compared to the ischemia and vehicle groups (P<0.001). Histologically, kidneys from the pirfenidone group exhibited a markedly lower injury score (score 2) relative to the ischemia and vehicle groups (score 4), indicating less tubular damage. The sham group showed no important histological abnormalities, with an injury score of 0.

Conclusion: Pirfenidone demonstrates substantial protective effects against renal ischemia-reperfusion injury in mice, evidenced by improvements in biochemical markers and decreased tissue damage. This suggests that pirfenidone holds potential as a therapeutic agent for preventing or ameliorating acute kidney injury.