Modulação das alterações funcionais e sintomáticas relacionadas à cistite hemorrágica induzida por ciclofosfamida em camundongos através do bloqueio medular dos canais de cálcio voltagem-dependentes dos subtipos P/Q e N

• Ano de defesa: 2014
• Autor(a) principal: Silva, Rodrigo Braccini Madeira da
• Orientador(a): Campos, Maria Martha
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Pontifícia Universidade Católica do Rio Grande do Sul
• Programa de Pós-Graduação: Programa de Pós-Graduação em Medicina e Ciências da Saúde
• Departamento: Faculdade de Medicina
• País: BR
• Palavras-chave em Português: MEDICINA; FARMACOLOGIA; CISTITE; INFLAMAÇÃO; EXPERIMENTAÇÃO ANIMAL
• Área do conhecimento CNPq: CNPQ::CIENCIAS DA SAUDE::MEDICINA
• Link de acesso: http://tede2.pucrs.br/tede2/handle/tede/1760

Spinal voltage-gated calcium channels (VGCC) are pivotal regulators of painful and inflammatory alterations, representing attractive therapeutic targets. We examined the effects of epidural administration of the selective P/Q- and N-type VGCC blockers Tx3-3 and Phα1β, respectively, isolated from the spider P. nigriventer, on symptomatic, inflammatory and functional changes allied to cyclophosphamide (CPA)-induced hemorrhagic cystitis (HC) in mice. The effects of P. nigriventer-derived toxins were compared to those displayed by MVIIC and MVIIA, extracted from the cone snail C. magus. HC was induced by a single intraperitoneal injection of CPA (300 mg/kg). The spinal blockage of P/Q-type VGCC by Tx3-3 and MVIIC, or N-type VGCC by Phα1β attenuated nociceptive and inflammatory events associated with HC, including bladder oxidative stress and cytokine production. Moreover, CPA produced an evident increase of bladder TRPV1 and TRPA1 mRNA expression, which was virtually reversed by all the tested toxins. Noteworthy, Phα1β strongly prevented bladder neutrophil migration, besides HC-related functional alterations. Finally, the spinal co-administration of the selective NK1 receptor antagonist CP-96345 heightened Phα1β antinociceptive effects. Our results shed new lights on the role of spinal P/Q and N-type VGCC in bladder dysfunctions, pointing out Phα1β as a promising alternative for treating complications associated to CPA-induced HC.