Nebivolol prevents redox imbalance and attenuates bladder dysfunction induced by cyclophosphamide in mice

Cyclophosphamide (CYP) is combined with cytoprotective agents to minimize its toxicity in the bladder, which is mediated by reactive oxygen species (ROS). Using multiple antioxidant mechanisms, nebivolol protects from oxidative stress in distinctive conditions. We hypothesized that nebivolol would attenuate both molecular and functional alterations induced by CYP in the bladder. Male C57BL/6 were pretreated or not with nebivolol (10 mg/kg/day, gavage), which was given 5 days before a single injection of CYP (300 mg/kg; i.p.). Molecular and functional parameters were assessed at 24 h in the bladder. Nebivolol prevented increases in ROS generation and lipoperoxidation as well as reduction of superoxide dismutase activity induced by CYP. Increased voiding frequency, decreased voiding interval, and reduced bladder capacity were found in CYP-treated mice. These responses were prevented by nebivolol. An augmented number of urinary spots and smaller urinary volumes were detected in CYP-injected mice, and nebivolol partially prevented these responses. The reduction of ROS levels is the primary mechanism by which nebivolol attenuates the deleterious effects of CYP in the bladder. The association of nebivolol with other cytoprotective agents could be an option to prevent CYP-associated oxidative damage to the bladder during chemotherapy.