Renoprotective Effect of Formononetin against Cyclophosphamide-Induced Oxidative Stress and Inflammation in Rat Kidney

Aims: Cyclophosphamide (CP) is a broad-spectrum chemotherapy agent available to treat various malignancies; however, its nephrotoxicity limits its clinical use. Formononetin (FOR) is a bioactive isoflavone with encouraging biological activities. The current study explored and elucidated the possible protective/therapeutic effects of formononetin against CP-induced nephrotoxicity.

Methodology: Rats received FOR (40 mg/kg/day) for 15 days followed by a single injection of CP on day 16. CP-induced nephrotoxicity is characterized by an increase in urea and creatinine levels in serum. Kidney homogenate was used to assess MDA, NO and antioxidants.

Results: CP-administered rats showed increased renal malondialdehyde and nitric oxide along with declined glutathione and antioxidant enzymes. In addition, CP increased pro-inflammatory cytokines and pro-apoptotic proteins levels and decreased anti-apoptotic protein Bcl2 levels in the kidney. FOR prevented CP-induced kidney injury, enhanced antioxidants and suppressed oxidative stress, pro-inflammatory mediators and apoptosis.

Conclusion: These findings suggest that FOR prevents CP nephrotoxicity by attenuating the oxidative damage and inflammation. Therefore, our data suggest that FOR may represent a novel protective strategy against CP-induced nephrotoxicity, which deserves pursuit in further studies.