Fluorofenidone inhibits nicotinamide adeninedinucleotide phosphate oxidase via PI3K/Akt pathway in the pathogenesis of renal interstitial fibrosis

Aim Oxidative stress plays an important role in the progression of renal interstitial fibrosis. The nicotinamide adeninedinucleotide phosphate ( NADPH ) oxidase ( N ox) family is considered one of the major sources of reactive oxygen species ( ROS ). In the present study, we investigated the inhibitory effects of a novel anti‐fibrotic agent, Fluorofenidone ( AKF‐PD ), upon N ox‐mediated oxidative stress and deposition of extracellular matrix ( ECM ) in the development of renalinterstitial fibrosis. Methods AKF‐PD was used to treat renal fibrosis in unilateral ureteral obstruction ( UUO ) obstructive nephropathy in rats. The expression of Nox homologues, p‐ A kt, collagen I and III were detected by immunoblotting or immunohistochemistry. Levels of 8‐iso prostaglandin F 2alpha (8‐ I so PGF2a ) was measured by enzyme linked immunosorbent assay. In addition, ROS and the expression of collagen I (1a), Nox subunits and p‐ A kt was measured in angiotensin ( A ng) II ‐stimulated rat proximal tubular epithelial ( NRK‐52E ) cells in culture. Results AKF‐PD treatment significantly attenuated tubulo‐interstitial injury, ECM deposition and oxidative stress in fibrotic rat kidneys. In addition, AKF‐PD inhibited the expression of ROS , Collagen I (1a), N ox2, p‐ A kt in A ng II ‐stimulated NRK ‐52 E cells. Conclusion AKF‐PD attenuates the progression of renal interstitial fibrosis partly by suppressing NADPH oxidase and ECM deposition via the PI3K/Akt signalling pathway, suggesting AKF‐PD is a potential novel therapeutic agent against renal fibrosis.