Anti-apoptotic effects of minocycline on doxorubicin-induced cardiotoxicity in male Wistar rats

Abstract

Background and Aim: Doxorubicin is an effective chemotherapeutic agent. However, use of this drug is limited due to its dose-dependent cardiotoxicity. Activation of apoptotic pathways in myocardial tissue plays an important role in doxorubicin- induced cardiotoxicity. Minocycline is an antibiotic that has anti-apoptotic effects. In this study, we investigated the protective effects of minocycline against doxorubicin-induced cardiac toxicity in male rats. Materials and Methods: Forty two adult male rats were divided into control (normal saline), doxorubicin (2.5 mg / kg), minocycline (45 and 90 mg / kg) and treatment (doxorubicin + minocycline 45 and 90 mg / kg) groups. Minocycline was injected intraperitoneally, once a day for 3 weeks. Ejection fraction (EF) and fractional shortening (FS) were measured using echocardiography. The activity of caspase 3/7 and the expression of Bax and Bcli were measured by biochemical methods. Bax and Bcl-2 genes expression levels were estimated by real-time PCR. Results: In the minocycline-treated groups (45 and 90 mg / kg) the activity of caspase 7/3 and the expression of Bax gene were significantly lower and the levels of EF, FS and Bcl-2 expression were significantly higher than those in the doxorubicin group. Conclusion: Minocycline reduces doxorubicin-induced cardiotoxicity. The anti-apoptotic effects of minocycline may play an important role in its protective effects.

Keywords

• doxorubicin
• minocycline
• cardiotoxicity
• apoptosis