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- (TNF-). The mean area percentage of collagen fiber content, caspase-3, eNOS, iNOS and TNF- 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- (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- modulation.