Efeito inibitório do decocto das folhas de Jatropha gossypiifolia L. contra a toxicidade local e sistêmica da peçonha da serpente Bothrops erythromelas

Abstract

Bothrops snakes are responsible for about 90% of snakebites in Latin America. Antivenom serum therapy, however, still has low efficacy against local effects, hard access in some regions, in addition to high cost and potential risk of adverse reactions. In this context, the main objective of this work is to contribute with complementary alternatives to antivenom therapy, with emphasis on the species Bothrops erythromelas, which is a snake of epidemiologic relevance in Northeastern Brazil, but that, until this moment, still lacks further studies and that is not included in the antigenic mixture for production of Brazilian bothropic antivenom. For this, two main work fronts were conducted: (1) characterization of the local and systemic toxic effects induced by this venom, in order to better understand its toxicity and thus to develop more effective strategies for its treatment; and (2) evaluation of the effectiveness of Jatropha gossypiifolia leaves decoction against the toxic effects of the venom under study, aiming at its use as raw material for future antiophidic herbal products, which may complement the efficacy of antivenom therapy. Through the experimental envenoming studies in mice, it was observed that B. erythromelas venom produced an intense local inflammatory picture, involving the direct participation of enzymatic components of the venom, as well as endogenous inflammatory mediators, which can be used as therapeutic targets for the treatment of local envenoming. In relation to systemic toxicity, venom produced in mice quite pronounced effects on hemostasis, in addition to systemic hemorrhage and renal and hepatic toxicity, which could be visualized by means of the alteration of several haematological, hemostatic and biochemical parameters. Through inhibition studies of these effects, it is observed that, in general, the tested antivenoms in fact have limited efficacy against the enzymatic activities in vitro and the local effects of the venom in vivo, despite the presence of immunological recognition, which indicates the presence of cross-reactivity with highly immunogenic but little toxicologically relevant components to the toxic action of the venom. Aqueous leaf extract of J. gossypiifolia, in turn, was able to significantly reduce the local and systemic effects of venom, which could be associated with its direct action on snake toxins, as well as an indirect action on the endogenous mediators. An herbal gel for use as a topical adjunct in the treatment of snake envenoming was developed and promising results were obtained when the association of this gel with antivenom was found to be able to significantly improve the efficacy of the treatment of local tissue damage induced by B. erythromelas. Phytochemical analyzes indicate that flavonoids are the major compounds of the plant species, and may be, at least partially, the main class of substance responsible for the activities presented. In conclusion, the results obtained to date demonstrate the potential of the plant species J. gossypiifolia as an adjuvant in the treatment of bothropic envenoming, and this study could be an initial kick-off for the future development of herbal antiophidic products with genuinely Brazilian raw material for complementation of the current antivenom therapy in the treatment of bothropic accidents.