Banca de DEFESA: SARAH DE SOUSA FERREIRA
Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.STUDENT : SARAH DE SOUSA FERREIRA
DATE: 22/06/2022
TIME: 14:00
LOCAL: Sala Carl Peter von Dietrich e Videoconferência - Link para acesso: meet.google.com/ocw-edtc-skj
TITLE:
Development and evaluation of antidotes for Bothrops brazili snake envenomation: investigation of the antivenom potential of chlorogenic and rosmarinic acids and antiserum production in chitosan nanoparticulate system
KEY WORDS:
Bothrops brazili. Nanotechnology. Ophidism. Phenolic compounds. Serotherapy.
PAGES: 199
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:
Ophidism causes high mortality and morbidity in many regions of the world. Currently, the only treatment is serum therapy, which has some limitations, such as: high cost for its production, low effectiveness in neutralizing local effects, difficult access in some regions and adverse reactions. Considering these factors, this study has the general objective of presenting new alternatives to improve the treatment of snakebite. For this purpose, the venom of the Bothrops brazili snake was used, a little studied species that is found mainly in the Amazon region. Thus, the present study has as specific objectives (1) to analyze the inhibitory potential of chlorogenic and rosmarinic acids against the local and systemic effects induced by B. brazili envenomation, (2) to obtain and characterize chitosan nanoparticles with the venom of this species with two modes of association (incorporation and adsorption), in order to be evaluated in relation to the immunoadjuvant potential for the production of a new serum. The evaluation of the antiophidic potential of chlorogenic and rosmarinic acids was carried out through in vitro, in vivo and in silico assays. In vitro, the acids were able to inhibit proteases and phospholipases activities of the venom, in addition to reducing the pro-coagulant effect in human plasma caused by the venom. In vivo, in a mouse model, these compounds inhibited local effects such as edema, hemorrhage, increased myeloperoxidase enzyme and myotoxicity. In silico the acids were able to interact with venom phospholipases. In addition, the compounds mitigated the systemic effects resulting from the envenomation, which were: kidney, liver, muscle damage, hemostatic changes (partially activated thromboplastin time, prothrombin time and platelet count), hematological (erythrogram and leukogram) and lipid peroxidation. For the production of chitosan nanoparticles, the ionic gelation technique was used. The nanoparticles had a size between 150 and 190 nm, a potential of approximately +30 mV and a polydispersity index (PDI) of approximately 0.400. These parameters were evaluated by the Dynamic Light Scattering (DLS) technique. The nanoparticles showed 97% efficiency to incorporate and adsorb the venom and the analysis of scanning electron microscopy with field emission source (MEVFEG) and atomic force microscopy (MFA) showed that they had homogeneous shape and size. Fourier transform infrared spectroscopy (FTIR) analysis revealed that the venom showed bands at 1543 cm-1 and 1651 cm-1 referring to amide groups. The nanoparticles showed bands at 916, 1087, 1259 and 1340 cm-1 that underwent deviation after incorporation and adsorption of the venom. In conclusion, these results demonstrate that chlorogenic and rosmarinic acids have the potential to inhibit the local and systemic effects caused by B. brazili envenomation, which makes them possible alternatives to complement serum therapy. Furthermore, chitosan nanoparticles were efficient in incorporating and adsorbing the venom, showing great potential to be used as an adjuvant in the production of a new antivenom.
BANKING MEMBERS:
Externo ao Programa - 1639820 - ARNOBIO ANTONIO DA SILVA JUNIOR - nullExterna à Instituição - DANIELA PRISCILA MARCHI SALVADOR - UFPB
Externo à Instituição - GISELLE PIDDE QUEIROZ - IB/SP
Interno - 2195251 - HUGO ALEXANDRE DE OLIVEIRA ROCHA
Presidente - 1544647 - MATHEUS DE FREITAS FERNANDES PEDROSA