A esponja oceanapia sp. Apresenta efeito dual sobre a motilidade gastrintestinal de roedores: ensaios in vitro e in vivo

• Autor(a) principal: Pereira, Joedna Cavalcante
• Data de Publicação: 2016
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UFPB
• Texto Completo: https://repositorio.ufpb.br/jspui/handle/tede/9498
• topic: Oceanapia sp; Esponja; Espasmogênico; Espasmolítico; Trânsito intestinal; Oceanapia sp; Sponge; Spasmogenic; Spasmolytic; Intestinal transit.; CIENCIAS BIOLOGICAS::FARMACOLOGIA

Marine natural products have attracted the attention of researchers due to be a potencial source to new medicines. Oceanapia sponges present around 100 species distributed on tropical worldwide seas. Some studies of marine products have shown activity in smooth muscle, however for Oceanapia sp. there is no report. So, we decided to assess the pharmacologic and toxicological activities of the ethanolic extract of Oceanapia sp. sponge (OC-EtOH). To in vitro assays (n = 5), guinea pig ileum segments were suspended on organ baths and isometric and isotonic contractions registrated. In the in vivo assays (n = 6), mice were divided in groups: negative control (saline + Cremophor®, v.o.), positive control (atropine, v.o.) and OC-EtOH (several doses, v.o.) where its were investigated the effect of the extract on normal and induced intestinal transit by castor oil. All the experimental protocols were approved by Ethical Committee in Animal Use of UFPB (Protocol 146/2015). In pharmacological screening, OC-EtOH induced a concentration dependent contraction on basal tonus on guinea pig ileum (EC50 = 48.6 ± 2.7 μg/mL). In tonic component of the contraction induced by KCl and histamine on guinea pig ileum, the extract presented a transient contraction (EC50 = 176.6 ± 32.6 and 73.5 ± 6.9 μg/mL, respectively), also followed by a concentration-dependent relaxation (EC50 = 103.9 ± 8.6 and 90.1 ± 9.2 μg/mL, respectively). Differently, when CCh was used as contractile agent, OC-EtOH presented only a concentration-dependent relaxation (EC50 = 97.1 ± 17.4 μg/mL). In the investigation of spasmogenic mechanism, we observed that in the presence of different concentrations of atropine, a muscarinic antagonist, the cumulative curves to OC-EtOH were not shifted. However, in the presence of pyrilamine, a receptor histaminergic antagonist (H1), the cumulative curves to OC-EtOH were shifted to the right, in a non-parallel manner with reduction on efficacy and potency and abolishment of spasmogenic effect, suggesting the involvement of H1 on spasmogenic effect of OC-EtOH. Similar result was obtained when used the verapamil, a voltage gated calcium channels blocker (CaV), that was added in different concentrations and the cumulative curves to OC-EtOH were shifted to the right, in a non-parallel manner with reduction on efficacy and potency spasmogenic, suggesting the mechanism of action of the extract also involves the CaV activation. In the investigation of spasmolytic mechanism, in pyrilamine presence, the spasmogenic component was abolished and the OC-EtOH relaxant potency was potentiated on the KCl-induced tonic contraction (EC50 = 62.9 ± 9.9 μg/mL). As the common pathway in the contractile agents used is the CaV, it has assessed these channels participation. The control curves to CaCl2 were shifted to the right, in a presence of extract, in a non-parallel manner with Emax reduction. Besides to relax the ileum pre-contracted by S-(-)-Bay K 8644 (EC50 = 166.9 ± 17.8 μg/mL), a CaV-1 agonist, showing that this channel subtype are involved. As the OC-EtOH relaxant potency was greater when the organ was pre-contracted with KCl + pyrilamine than S-(-)-Bay K 8644 was the contractile agent, it is suggestive that other mechanism are probably involved. In acute toxicity assay, OC-EtOH (2000 mg/kg, p.o.) did not induce toxicity signs in female mice (n = 6) in the experimental conditions and the 50% lethal dose is equal or superior to 5000 mg/kg according to OECD 423 guide. Since some compounds with dual action (spasmolytic and spasmogenic) on smooth muscle are indicated to diarrhea and constipation treatment, it was investigate a possible OC-EtOH presents antidiarrheal action on mice. The extract increased the intestinal normal transit (ED50 = 477.6 ± 14.8 mg/kg) and reduced the intestinal transit in the ricin oil induced diarrhea (ED50 = 93.30 ± 7.2 mg/kg). Thus, OC-EtOH presented a dual effect on guinea pig ileum by H1 and CaV activation and relaxation via CaV blockade, besides intestinal transit effect in mice that occurs by modification in the intestinal motility, indicating a potential medicinal usage of the sponje Oceanapia sp. on intestinal conditions as diarrhea and/or constipation.