Reno-protective effect of Roflumilast against kidney injury induced by ischemia/reperfusion in rats: Evidence from biochemical and histological investigations

Oxidative stress, inflammation, and apoptosis are major contributors to renal ischemia/reperfusion (I/R) injury. This study aimed to investigate the effects of pretreatment with the PDE4 inhibitor roflumilast (Rof) on renal I/R and its underlying mechanisms. Sprague-Dawley rats were subjected to 30 minutes of unilateral renal ischemia followed by 45 minutes of reperfusion. Rof (1.5 and 3 mg/kg) was administered for seven days prior to I/R induction. The findings showed that Rof significantly and dose-dependently attenuated kidney damage by reducing blood urea nitrogen and creatinine levels. Rof also exhibited antioxidant and anti-inflammatory effects, as evidenced by improved glutathione and malondialdehyde levels and decreased proinflammatory cytokines (IL-6 and TNF-α). Furthermore, Rof prevented the downregulation of HO-1 and Nrf2 expression. These results suggest that Rof therapy could protect the kidneys from I/R-induced injury through its antioxidant and anti-inflammatory properties, providing a potential therapeutic approach for the management of renal I/R damage.