Estudo da atividade antinociceptiva e possíveis mecanismos de ação do ácido oleanólico em modelos de nocicepção induzida por capsaicina e óleo de mostarda em camundongos

• Autor(a) principal: Maia, Juliana Lemos
• Data de Publicação: 2006
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
• dARK ID: ark:/83112/001300000vmh2
• Texto Completo: http://www.repositorio.ufc.br/handle/riufc/2448
• topic: Ácido Oleanólico; Óxido Nítrico

Oleanolic acid is a triterpene pentacyclic widely distributed in the plant kingdom. Different biologic activities have been reported including: antiinflammatory, hepatoprotective, gastroprotective and antinociceptive. This work was aimed to evaluate the antinociceptive effect of oleanolic acid in acute nociception models induced by capsaicin (20µl/ 1.6 μg) and mustard oil (0.75%, 50 µL/animal) in mice and to establish the likely mechanism(s) of action. Mice were pretreated orally with oleonolic acid (3, 10, 30 and 100 mg/kg) or vehicle, and the pain-related behavioral responses were analysed. The pain behavioral responses were significantly suppressed at doses 10, 30 and 100 mg/kg in acute nociception models induced by capsaicin and mustard oil. The maximal suppression (p<0.001) was observed at the dose of 30 mg/kg. In order to verify the possible mechanisms involved in the antinociceptive action of oleanolic acid in the capsaicin-induced nociception, the involvement of endogenous opioids, α2, nitric oxide and KATP channels were analyzed. The antinociception produced by OA (30 mg/kg, v.o.) was found to be significantly blocked in animals pre-treated with the opioid antagonist, naloxone (2 mg/kg, i.p.); the substrate for oxide nitric synthase, L-arginine (600 mg/kg, i.p.); or a KATP-channel blocker, glibenclamide (2 mg/kg, i.p.) but was unaffected by yohimbine (2 mg/kg, i.p.), an α2 -adrenoceptor antagonist. In order to verify the possible mechanisms involved in the antinociceptive action of oleanolic acid in the mustard oil-induced visceral pain model, opioid, α2 adreno and TRPV1 receptors were analyzed. The antinociceptive effect of oleanolic acid (30 mg/kg, v.o.) was significantly blocked (p<0.05) by pretreatment with the opioid antagonist, naloxone (2 mg/kg, i.p.), but the α2-adrenoceptor antagonist, yohimbine (2 mg/kg, s.c.), had no effect. Pretreatment with ruthenium red (3 mg/kg, s.c.), a non-competitive TRPV1 antagonist alone caused significant inhibition (p<0.01) of mustard oil-induced nociception but its co-administration with oleanolic acid produced neither antagonism nor potentiation of oleonolic acid antinociception. Further, to evaluate a possible motor impairment and motor incoordination effects related to oleanolic acid, open-field and rota-rod tests were performed. The data indicated that the treatment of animals with the oleanolic acid (30 mg/kg, v.o.) was unable to cause motor impairment or motor incoordination effects (p>0.05), being even able to reverse (p<0.05) a mustard oil-induced motor impairment in the open field test. The results taken together strongly suggest the therapeutic potential of oleanolic acid in oblitering nociception through the mechanisms that possibly involve the opioids, TRPV1 receptors, nitric oxide and KATP channels.