Abarema cochliacarpos extract decreases the inflammatory process and skeletal muscle injury induced by Bothrops leucurus venom.

Snakebites are a public health problem, especially in tropical countries. However, treatment with antivenom has limited effectiveness against venoms' local effects. Here, we investigated the ability of Abarema cochliacarpos hydroethanolic extract (EAc) to protect mice against injection of Bothrops leucurus venom. Swiss mice received perimuscular venom injection and were subsequently treated orally with EAc in different doses. Treatment with EAc 100, 200, and 400 mg/kg reduced the edema induced by B. leucurus in 1%, 13%, and 39%, respectively. Although lower doses showed no antihypernociceptive effect in the Von Frey test, the higher dose significantly reduced hyperalgesia induced by the venom. Antimyotoxic activity of EAc was also observed by microscopy assessment, with treated muscles presenting preserved structures, decreased edema, and inflammatory infiltrate as compared to untreated ones. Finally, on the rotarod test, the treated mice showed better motor function, once muscle fibers were preserved and there were less edema and pain. Treated mice could stand four times more time on the rotating rod than untreated ones. Our results have shown that EAc presented relevant activities against injection of B. leucurus venom in mice, suggesting that it can be considered as an adjuvant in the treatment of envenomation.

Dexamethasone antagonizes the in vivo myotoxic and inflammatory effects of Bothrops venoms.

In the present work we investigated the toxic activities of two Bothrops snake venoms using in vivo and in vitro experimental protocols in mice and tested the protective effect of dexamethasone (DEXA) in different conditions, comparing it with the polyvalent antivenom. We also expanded the investigations on the antiophidic effect of the Eclipta prostrata (EP) crude extract. The administration of Bothrops jararaca and Bothrops jararacussu snake venoms induced muscle damage demonstrated in vivo by the elevation on plasma creatine kinase (CK) activity in mice and by the decrease in CK content in the extensor digitorum longus (EDL) muscle of these animals, and in vitro by the increase in the rate of CK release from the isolated EDL muscle. We also observed inflammatory response following perimuscular injection of B. jararacussu venom (1.0 mg/kg). Treatment with DEXA (1.0 mg/kg) preserved over 50% of the EDL muscle CK content in vivo when evaluated 24 and 72 h after the injection of B. jararacussu venom in mice, and likewise reduced about 20% of the edema induced by this venom. DEXA reduced in 50% the presence of inflammatory cells and their activity in EDL muscle. The EP extract (50 mg/kg) showed similar ability in preventing the induction of edema and the decrease in muscle CK content, and its association with DEXA showed additive effect. EP reduced over 77% of the plasma CK activity induced by the B. jararacussu venom. In the in vitro experiments, DEXA was not able to change the rate of CK release from EDL muscles exposed to 25 µg/mL of B. jararacussu venom, neither to prevent the fall in the amplitude of the indirectly evoked twitch at the phrenic-diaphragm preparation. EP extract showed otherwise a protective effect on these protocols, reaching up to 100% of protection when concentrations of 50.0 and 100.0 µg/mL were used. Altogether our results show that inflammation is at least in part responsible for the tissue damage induced by Bothrops snake venoms, once the steroidal anti-inflammatory drug dexamethasone was able to decrease the myotoxic effects of these venoms, by reducing the inflammatory response to the venom injection.

Antiophidic activity of the extract of the Amazon plant Humirianthera ampla and constituents.

ETHNOPHARMACOLOGICAL RELEVANCE: Although serotherapy against snakebite has been discovered more than one hundred years ago, antivenom is not available all over Brazil. The use of plants from folk medicine is common mainly in the Brazilian Amazon area. One of these plants is named Humirianthera ampla (HA). MATERIALS AND METHODS: We have investigated HA extract and constituents' antiophidic activity in different experimental protocols against some Bothrops snake venoms (Bothrops jararacussu, Bothrops atrox and Bothrops jararaca). The protocols investigated include phospholipase, proteolytic, pro-coagulant, hemorrhagic, edematogenic and myotoxic activities induced by these venoms in Swiss mice. RESULTS: All the venoms caused an increase in the rate of creatine kinase (CK) release from isolated muscles, indicating damage to the sarcolemma. The crude extract of HA decreased the myotoxic activity in a concentration-dependent fashion. The presence of HA 300 µg/mL decreased up to 96% of Bothrops jararacussu and 94% of Bothrops atrox myotoxicity after 90 min of exposure. In vivo myotoxicity of Bothrops atrox venom was decreased in 75% when the venom was preincubated with HA 500 mg/kg. Similar results were observed with lupeol against Bothrops jararacussu and Bothrops atrox venoms. The hemorrhagic activity was evaluated by intradermal injection of Bothrops atrox venom. Preincubation and oral pre- and posttreatment with HA decreased hemorrhage by 100%, 45% and 45%, respectively. Bothrops atrox venom also induced formation of edema, which was significantly inhibited by pre- and posttreatment with HA. All the venoms showed extensive pro-coagulating properties, and these activities were inhibited by up to 90% with HA, which presented concentration-dependent inhibition. Finally, proteolytic and phospholipase activities of the venoms were all inhibited by increasing concentrations of HA, lupeol and sitosterol. The inhibition of these activities might help explain the actions against in vivo myotoxicity and the in vivo effects observed, i.e., edema, myotoxicity, pro-coagulation and hemorrhage. CONCLUSIONS: Altogether, our results give support for the popular use of HA extracts in cases of accidents with snakes, suggesting that it can be used as an adjunct in the management of venomous snakebites.