RESUMO
Snake venoms contain various bradykinin-potentiating peptides (BPPs). First studied for their vasorelaxant properties due to angiotensin converting enzyme (ACE) inhibition, these molecules present a range of binding partners, among them the argininosuccinate synthase (AsS) enzyme. This has renewed interest in their characterization from biological sources and the evaluation of their pharmacological activities. In the present work, the low molecular weight fraction of Bothrops moojeni venom was obtained and BPPs were characterized by mass spectrometry. Eleven BPPs or related peptides were sequenced, and one of them, BPP-Bm01, was new. Interestingly, some oxidized BPPs were detected. The three most abundant peptides were BPP-Bm01, BPP-Bax12, and BPP-13a, and their putative interactions with the AsS enzyme were investigated in silico. A binding cavity for these molecules was predicted, and docking studies allowed their ranking. Three peptides were synthesized and submitted to vasorelaxation assays using rat aortic rings. While all BPPs were active, BPP-Bm01 showed the highest potency in this assay. This work adds further diversity to BPPs from snake venoms and suggests, for the first time, a putative binding pocket for these molecules in the AsS enzyme. This can guide the design of new and more potent AsS activators.
Assuntos
Aorta , Bothrops , Oligopeptídeos , Peptídeos , Serpentes Peçonhentas , Animais , Ratos , Brasil , Aorta/efeitos dos fármacos , Peptídeos/farmacologia , Peptídeos/química , Bradicinina/farmacologia , Masculino , Venenos de Crotalídeos/farmacologia , Venenos de Crotalídeos/química , Ratos Wistar , Venenos de Serpentes/farmacologia , Vasodilatadores/farmacologia , Vasodilatadores/química , Estrutura MolecularRESUMO
This study aims to evaluate the hepatoprotective, hypolipidemic and aortic morphometric effects of fish oil rich in omega-3 in hypercholesterolemic BALB/c mice. This is an experimental model that included 16 male BALB/c mice (Mus musculus) divided into three groups (G1 (standard commercial chow and 0.9% saline solution), G2 (hypercholesterolemic diet and 0.9% saline solution) and G3 (hypercholesterolemic diet and fish oil)) for 8 weeks. There was no significant difference in the treatment with omega-3-rich fish oil in the lipid profile (p > 0.05). In the histological analysis, group G2 detected the presence of hepatitis and liver tissue necrosis, but this was not observed in group G3. As for the morphometry in the light area of the vessel, the G1 group had a higher score (2.62 ± 0.36 mm2) when compared to G2 (2.10 ± 0.16 mm2) and G3 (2.26 ± 0.25 mm2) (p < 0.05). The vessel wall thickness did not differ between the groups (p > 0.05). It is concluded that supplementation with fish oil rich in omega-3 carried out in this study may have a protective effect on liver tissue, but it has not yet improved the lipid and morphometric profile. Despite this research being preliminary, it is a relevant study with future prospects for improving the doses of EPA and DHA in order to better elucidate the benefits of fish oil in models of dyslipidemia.