Protective effect of nebivolol on doxorubicin-induced cardiotoxicity in rats

Introduction: The cardiotoxicity of doxorubicin is incompletely understood. We investigated the prophylactic effect of nebivolol on doxorubicin-induced cardiac toxicity. Material and methods: Thirty rats were divided into a control group, doxorubicin-treated group and nebivolol + doxorubicin-treated group. The specimens were examined using H + E and Masson's trichrome, caspase 3, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and tumor necrosis factor factor-alpha (TNF-alpha). The mean area percentage of collagen fiber content, caspase-3, eNOS, iNOS and TNF-alpha immunoactivities was measured. Results: The doxorubicin-treated group showed marked myocyte distortion and fragmentation, congestion and cytoplasmic lysis in most fibers. These changes were less intense in the nebivolol-treated group. The mean area percentage of collagen fiber in the nebivolol-treated group was non-significantly smaller (p = 0.07) than that in the doxorubicin-treated group. The expression of caspase-3 (p = 0.03), eNOS (p <= 0.001), iNOS (p < 0.001) and TNF-alpha (p = 0.003) immunoreactivity was improved in the nebivolol-treated group. Conclusions: Nebivolol exerted a significant protective effect from doxorubicin toxicity. The protective effect appears to be mediated mainly through caspase-3, eNOS, iNOS and TNF-alpha modulation.