Analysis of the Inhibitory Potential of Chlorogenic Acid and Rosmarinic Acid against the Effects of Bothrops leucurus WAGLER (1824) snake venom
Antiophidic activity; Phenolic compounds; Bothrops leucurus; Neutralization of toxins.
Snakebites represent a serious public health problem in tropical countries, given the high rate of occurrences and the morbidity/mortality they cause. The snake Bothrops leucurus is one of the main responsible for the snakebites reported in Northeastern Brazil, however, this species is not included in the pool of venoms that are used in the production of the Brazilian antivenom serum, which may compromise the effectiveness of the clinical treatment. Additionally, the antivenom has limited effectiveness in mitigating local effects of envenomation and presenting logistical distribution problems, as well as reported the occurrence of adverse reactions. In this context, several studies have been carried out in order to develop complementary treatments for the effects of envenomation, and medicinal plants have stood out in this field, representing an important source of compounds with potential to help in the treatment of envenomation. Chlorogenic acid and rosmarinic acid are molecules derived from the secondary metabolism of plants, with antioxidant, anti-inflammatory and anticoagulant reported properties, among others, but the antivenom potential of both compounds is still poorly explored. Thus, our objective was to evaluate the inhibitory potential of chlorogenic acid and rosmarinic acid in the toxicity triggered by the B. leucurus snake venom and one of its enhanced phospholipase A2. Initially, an in vitro neutralization capacity of toxins was evaluated, which were analyzed as phospholipase A2, hyaluronidase, protease, fibrongenolytic and coagulant activities. Then, in vivo tests were performed to verify the inhibition of both acids against the local effects in mice, with assays of hemorrhagic, edematogenic, myotoxic, myeloperoxidase activity and interleukin production. Additionally, the inhibition of systemic toxicity was evaluated through changes in several biochemical, hemostatic and hematological markers, as well as lipid peroxidation in organs. The results showed that both acids inhibited in vitro enzymatic activities of the venom, mainly the hyaluronidase activity. In in vivo assays, both acids demonstrated inhibition of edema, with decreased myeloperoxidase activity and interleukin expression. The inhibitors also significantly attenuated the hemorrhagic and myotoxic actions of the venom. In serum biochemical markers, both compounds attenuated the changes in evalueted parameters and decreased the level of lipid peroxidation in liver and kidney tissues. However, when evaluating hemostatic parameters, only rosmarinic acid was able to reduce the effects on circulating fibrinogen and platelet count. Taken together, the results obtained show the antivenom potential of chlorogenic and acids, which showed, in general, greater inhibition efficiency than antivenom serum. Thus, both inhibitors are promising candidates for development of future adjuvants to be used for complement the antivenom sorotherapy currently available.