Effects of curcumin on cyclosporine A-induced oxidative stress, autophagy, and apoptosis in rat heart.

Abstract

Background: Cyclosporine A (CsA) is a powerful immunosuppressant commonly used as a prophylaxis on transplant. However, it is associated with serious effects, including cardiotoxicity. Curcumin is a bioactive compound known for its anti-oxidative, anti-inflammatory, and anti-apoptotic effects. So, the present study investigated the possible protective effect of curcumin on CsA-induced heart injury in rats, focusing on oxidative stress, autophagy, and apoptosis.

Methods: A total of 32 male Wistar rats were divided into control, sham (drug solvent), CsA (30 mg/kg BW), and curcumin + CsA (40 mg/kg BW, 30 mg/kg BW, respectively) groups. After 4 weeks of treatment, the heart was isolated for molecular assays. Immunoblot detected oxidative and autophagic proteins NOX4, hsp-70, beclin-1, and LC3II. The amount of 8-OHdG was measured by ELISA and heart apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining (TUNEL).

Results: At the molecular levels, CSA increased the expression of NOX-4, beclin-1, LC3b, and oHdG in heart tissue. In addition, the amount of apoptosis increased in the heart tissue. However, curcumin treatment improved heart injury by significantly downregulating NOX4, LC3b, and decreasing 8-OHdG. Also, curcumin significantly reduced the rate of myocardial apoptosis.

Conclusion: To sum up, curcumin appears to protect against CsA-induced cardiotoxicity in rats by reducing oxidative activity, apoptosis, and regulating autophagy.