Programa de Pós-Graduação em Ciências Farmacêuticas
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Doctoral Thesis Potencial da espécie vegetal Jatropha molissima (Pohl) Baill. contra os efeitos tóxicos da serpente Bothrops jararaca e do escorpião Tityus serrulatus(2019-06-27) Gomes, Jacyra Antunes dos Santos; Pedrosa, Matheus de Freitas Fernandes; ; ; Freitas, Janaina Cristiana de Oliveira Crispim; ; Machado, Paula Renata Lima; ; Soares, Luiz Alberto Lira; ; Lima, Maira Conceição Jerônimo de Souza;Accidents caused by venomous animals are a serious public health problem. In Brazil, most accidents are associated with snakes of the genus Bothrops and the scorpion of the genus Tityus. Currently, the main available treatment is the antivenom serum therapy, which has some limitations, such as inability to neutralize local effects, risks of immunological reactions, high cost and difficult access in some regions. In this context, the search for new complementary alternatives to treat venomous animals is relevant. Jatropha mollissima (Pohl) Baill., (Euphorbiaceae), a medicinal plant popularly known in Brazil as "pinhão bravo" is very used in folk medicine as antiophidic and antiinflammatory. Given the relevance of systemic effects of B. jararaca venom and T. serrulatus venom envenoming, the aim of the present work was evaluate the inhibitory efficacy of aqueous extract from leaves of J. mollissima upon systemic effects induced by these venoms. The effect of oral treatment with aqeous extract upon hematological, hemostatic, biochemical alterations and oxidative stress in response to B. jararaca vemom injection was evaluated in mice; and pulmonary edema, biochemical alterations and oxidative stress produced in response to T. serrulatus venom. Extract reduced significantly the effect of venom upon fibrinogen, platelets and activated partial thromboplastin time (APTT), indicating the action of extract upon hemostatic effects of B. jararaca venom. The extract also inhibited B. jararaca venom effects on leukocyte blood series, which indicates benefitial effects upon inflammatory processes. The extract was also able to reduce significantly the renal, hepatic, muscular and pancreatic toxicity of B. jararaca venom, by reverting the effects upon serum levels of urea, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and amylase. The extract inhibited the hepatic and renal oxidative stress of B. jararaca venom, indicating a possible antioxidant action. In addition, pulmonary edema induced by T. serrulatus venom was inhibited significantly by extract. Myeloperoxidase and IL-6 and IL-1β cytokines were reduced in the presence of extract, indicating benefitial effects upon inflammatory processes. The extract was also able to reduce significantly the renal, hepatic, muscular and pancreatic toxicity of T. serrulatus venom, by reverting the effects upon serum levels LDH, creatine kinase (CK), urea, creatinine, AST and amylase suggesting an inhibition of hepatic, renal and pancreatic damage. The extract inhibited the hepatic and renal oxidative stress of T. serrulatus venom, indicating a possible antioxidant action. In vitro, J. mollissima was able to inhibit hemolysis and cytotoxicity against MDCK cells, indicating that the absence of toxicity and, finally, the extract showed antioxidant activity in different models. Thus, it is concluded that the extract of J. mollissima posseses compounds able of decresae systemic alterations induced by B. jararaca and T. serrulatus, indicating the potentiality of this vegetal species as a source of bioactive molecules against bothropic and scorpionic venoms.Master Thesis Inibição dos efeitos locais induzidos pelas peçonhas das serpentes Bothrops erythromelas e Bothrops jararaca pelo extrato aquoso das folhas de Jatropha mollissima (Pohl) Bail(Universidade Federal do Rio Grande do Norte, 2015-03-27) Gomes, Jacyra Antunes dos Santos; Pedrosa, Matheus de Freitas Fernandes; ; http://lattes.cnpq.br/2929963416385218; ; http://lattes.cnpq.br/7321565101717558; Guerra, Gerlane Coelho Bernardo; ; http://lattes.cnpq.br/5677318431530876; Queiroz, Giselle Pidde; ; http://lattes.cnpq.br/7495278358369848Snakebites are a serious public health problem in tropical and subtropical countries and Bothrops genus is responsible for the accidents in Brazil and throughout Latin America (90% of cases). The local effects (pain, edema, hemorrhage and myonecrosis) and systemic (cardiovascular alterations, shock and blood clotting disorders) caused by the venom of Bothrops are due to the numerous protein and non-protein components, which are part of the constitution of the poison. The only form of therapy is scientifically validated antivenom serum therapy which, however, is not effective with respect to local effects produced, risk of immunological reactions, high cost and difficult access in some regions. Thus, the search for new alternatives to serum therapy becomes important, and in this context, many medicinal plants have been highlighted by the popular use as antiophidic. Among these plants, we can mention the species Jatropha mollissima (Euphorbiaceae) which has popular use in traditional medicine as antiophidic, anti-inflammatory, antimicrobial and antipyretic. Therefore, this study aims to evaluate the neutralizing potential of local effects induced by the venom of Bothrops erythromelas and Bothrops jararaca with the aqueous extract of the leaves of J. mollissima. The leaf extracts were prepared by decoction, fractionated (by liquid-liquid partition) and characterized by thin layer chromatography (TLC) and High Performance Liquid Chromatography (HPLC). Antiophidic activity of the extract was evaluated in model of paw edema, peritonitis, bleeding and myotoxicity induced by venoms of B. jararaca and B. erythromelas. In all models, the extract was evaluated by intraperitoneal route at the doses of 50, 100 and 200 mg/kg, administered 30 minutes prior to injection of the venom (pretreatment protocol). Stains suggestive of the presence of flavonoids: apigenin, luteolin, orientin, isoorientin, vitexin and vitexin-2-O-rhamnoside were detected in the extract by co-CCD. By means of HPLC were identified isoorientin, orientin, vitexin and isovitexin. All tested doses of J. mollissima extract reduced the paw edema induced by the venom with intensity similar to dexamethasone. The aqueous extract of J. mollissima leaves on all evaluated doses, inhibited cell migration induced by B. jararaca and B. erythromelas promoting inhibition of recruitment of mononuclear cells and the polymorphonuclear cells. Local bleeding induced by B. jararaca venom was significantly inhibited by the extract. Both venoms were inhibited by the extract in myotoxic activity. These results indicate that the aqueous extract of J. mollissima leaves have snakebite potential, particularly with respect to local effects, which may justify the use of this plant in traditional medicine and complementary therapy as anti-venom serum.