RESUMO
Schistosomiasis is a parasitic disease that affects more than 250 million people. The treatment is limited to praziquantel and the control of the intermediate host with the highly toxic molluscicidal niclosamide. Marine algae are a poorly explored and promising alternative that can provide lead compounds, and the use of multivariate analysis could contribute to quicker discovery. As part of our search for new natural compounds with which to control schistosomiasis, we screened 45 crude extracts obtained from 37 Brazilian seaweed species for their molluscicidal activity against Biomphalaria glabrata embryos and schistosomicidal activities against Schistosoma mansoni. Two sets of extracts were taxonomically grouped for metabolomic analysis. The extracts were analyzed by GC-MS, and the data were subjected to Pattern Hunter and Pearson correlation tests. Overall, 22 species (60%) showed activity in at least one of the two models. Multivariate analysis pointed towards 3 hits against B. glabrata veliger embryos in the Laurencia/Laurenciella set, 5 hits against B. glabrata blastula embryos, and 31 against S. mansoni in the Ochrophyta set. Preliminary annotations suggested some compounds such as triquinane alcohols, prenylated guaianes, dichotomanes, and xenianes. Despite the putative identification, this work presents potential candidates and can guide future isolation and identification.
Assuntos
Biomphalaria/efeitos dos fármacos , Bioprospecção , Descoberta de Drogas , Moluscocidas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/prevenção & controle , Esquistossomicidas/farmacologia , Alga Marinha/metabolismo , Animais , Biomphalaria/parasitologia , Brasil , Metaboloma , Metabolômica , Moluscocidas/isolamento & purificação , Schistosoma mansoni/crescimento & desenvolvimento , Esquistossomose mansoni/parasitologia , Esquistossomicidas/isolamento & purificaçãoRESUMO
Schistosomiasis is a parasitic disease that affects more than 250 million people. The treatment is limited to praziquantel and the control of the intermediate host with the highly toxic molluscicidal niclosamide. Marine algae are a poorly explored and promising alternative that can provide lead compounds, and the use of multivariate analysis could contribute to quicker discovery. As part of our search for new natural compounds with which to control schistosomiasis, we screened 45 crude extracts obtained from 37 Brazilian seaweed species for their molluscicidal activity against Biomphalaria glabrata embryos and schistosomicidal activities against Schistosoma mansoni. Two sets of extracts were taxonomically grouped for metabolomic analysis. The extracts were analyzed by GC–MS, and the data were subjected to Pattern Hunter and Pearson correlation tests. Overall, 22 species (60%) showed activity in at least one of the two models. Multivariate analysis pointed towards 3 hits against B. glabrata veliger embryos in the Laurencia/Laurenciella set, 5 hits against B. glabrata blastula embryos, and 31 against S. mansoni in the Ochrophyta set. Preliminary annotations suggested some compounds such as triquinane alcohols, prenylated guaianes, dichotomanes, and xenianes. Despite the putative identification, this work presents potential candidates and can guide future isolation and identification
RESUMO
Isoflurane is a halogenated ether which is used for general anesthesia. To stabilize a new formulation in order to evaluate the potential to reduce the dose required for general anesthesia, an isoflurane-loaded nanoemulsion was proposed. A high-pressure homogenization technique was used to develop drug-loaded nanoemulsions which presented droplet size of 150 +/- 0.78 nm with a narrow size distribution and low polydispersity index (0.08 +/- 0.01). The zeta potential was -18 +/- 2.4 mV and pH was 6.03 +/- 0.04. Rheological analysis showed Newtonian behavior for the formulations, whose physical stability was confirmed by multiple light scattering. It was verified that isoflurane volatilization did not occur in these formulations. The preclinical evaluation, carried out via the end-tidal isoflurane concentration, showed that the dose required for anesthetic maintenance significantly decreased when the nanostructured formulation was administered compared to inhaled isoflurane. There was no significant difference (p < 0.05) between experimental groups (inhaled isoflurane and intravenous isoflurane-loaded nanoemulsion) in terms of the cardiac rate, oxygen hemoglobin saturation, and arterial blood pressure, as well as the biomarkers of renal, hepatic and skeletal muscle system functionalities. Slight tachypnea, edema, and erythema were observed after isoflurane-loaded or unloaded-nanoemulsion. The stability and significant dose reduction observed for drug-loaded nanoemulsion render this formulation a promising option for intravenous delivery of isoflurane.