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

Autor:	Jesus CPS; Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.; Programa de Pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil., Pimenta GF; Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.; Programa de Pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil., de Oliveira MG; Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo, Brazil., Dourado TMH; Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.; Programa de Pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil., Antunes E; Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo, Brazil., Tirapelli CR; Laboratório de Farmacologia, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.; Departamento de Ciências BioMoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Ribeirão Preto, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Canadian journal of physiology and pharmacology [Can J Physiol Pharmacol] 2024 Dec 01; Vol. 102 (12), pp. 729-740. Date of Electronic Publication: 2024 Sep 13.
DOI:	10.1139/cjpp-2024-0064
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest associated with this work.
Databáze:	MEDLINE
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