Lapachol and synthetic derivatives: in vitro and in vivo activities against Bothrops snake venoms.

BACKGROUND: It is known that local tissue injuries incurred by snakebites are quickly instilled causing extensive, irreversible, tissue destruction that may include loss of limb function or even amputation. Such injuries are not completely neutralized by the available antivenins, which in general are focused on halting systemic effects. Therefore it is prudent to investigate the potential antiophidic effects of natural and synthetic compounds, perhaps combining them with serum therapy, to potentially attenuate or eliminate the adverse local and systemic effects of snake venom. This study assessed a group of quinones that are widely distributed in nature and constitute an important class of natural products that exhibit a range of biological activities. Of these quinones, lapachol is one of the most important compounds, having been first isolated in 1882 from the bark of Tabebuia avellanedae. METHODOLOGY/PRINCIPAL FINDINGS: It was investigated the ability of lapachol and some new potential active analogues based on the 2-hydroxi-naphthoquinone scaffold to antagonize important activities of Bothrops venoms (Bothrops atrox and Bothrops jararaca) under different experimental protocols in vitro and in vivo. The bioassays used to test the compounds were: procoagulant, phospholipase A2, collagenase and proteolytic activities in vitro, venom-induced hemorrhage, edematogenic, and myotoxic effects in mice. Proteolytic and collagenase activities of Bothrops atrox venom were shown to be inhibited by lapachol and its analogues 3a, 3b, 3c, 3e. The inhibition of these enzymatic activities might help to explain the effects of the analogue 3a in vivo, which decreased skin hemorrhage induced by Bothrops venom. Lapachol and the synthetic analogues 3a and 3b did not inhibit the myotoxic activity induced by Bothrops atrox venom. The negative protective effect of these compounds against the myotoxicity can be partially explained by their lack of ability to effectively inhibit phospholipase A2 venom activity. Bothrops atrox venom also induced edema, which was significantly reduced by the analogue 3a. CONCLUSIONS: This research using a natural quinone and some related synthetic quinone compounds has shown that they exhibit antivenom activity; especially the compound 3a. The data from 3a showed a decrease in inflammatory venom effects, presumably those that are metalloproteinase-derived. Its ability to counteract such snake venom activities contributes to the search for improving the management of venomous snakebites.

True or false coral snake: is it worth the risk? A Micrurus corallinus case report.

BACKGROUND: Bites provoked by the genus Micrurus represent less than 1% of snakebite cases notified in Brazil, a tiny fraction compared with other genus such as Bothrops and Crotalus, which together represent almost 80% of accidents. In addition to their less aggressive behavior, habits and morphology of coral snakes are determinant factors for such low incidence of accidents. Although Micrurus bites are rare, victims must be rescued and hospitalized in a short period of time, because this type of envenoming may evolve to a progressive muscle weakness and acute respiratory failure. CASE PRESENTATION: We report an accident caused by Micrurus corallinus involving a 28-year-old Caucasian sailor man bitten on the hand. The accident occurred in a recreational camp because people believed the snake was not venomous. The victim presented neurological symptoms 2 h after the accident and was taken to the hospital, where he received antielapidic serum 10 h after the bite. After the antivenom treatment, the patient presented clinical evolution without complications and was discharged 4 days later. CONCLUSIONS: We reinforce that it is essential to have a health care structure suitable for the treatment of snakebite. Besides, the manipulation of these animals should only be carried out by a team of well-equipped and trained professionals, and even so with special attention.

True or false coral snake: is it worth the risk? A Micrurus corallinus case report

Bites provoked by the genus Micrurus represent less than 1% of snakebite cases notified in Brazil, a tiny fraction compared with other genus such as Bothrops and Crotalus, which together represent almost 80% of accidents. In addition to their less aggressive behavior, habits and morphology of coral snakes are determinant factors for such low incidence of accidents. Although Micrurus bites are rare, victims must be rescued and hospitalized in a short period of time, because this type of envenoming may evolve to a progressive muscle weakness and acute respiratory failure. Case Presentation We report an accident caused by Micrurus corallinus involving a 28-year-old Caucasian sailor man bitten on the hand. The accident occurred in a recreational camp because people believed the snake was not venomous. The victim presented neurological symptoms 2 h after the accident and was taken to the hospital, where he received antielapidic serum 10 h after the bite. After the antivenom treatment, the patient presented clinical evolution without complications and was discharged 4 days later. Conclusions: We reinforce that it is essential to have a health care structure suitable for the treatment of snakebite. Besides, the manipulation of these animals should only be carried out by a team of well-equipped and trained professionals, and even so with special attention.(AU)

True or false coral snake: is it worth the risk? A Micrurus corallinus case report

Background Bites provoked by the genus Micrurus represent less than 1% of snakebite cases notified in Brazil, a tiny fraction compared with other genus such as Bothrops and Crotalus, which together represent almost 80% of accidents. In addition to their less aggressive behavior, habits and morphology of coral snakes are determinant factors for such low incidence of accidents. Although Micrurus bites are rare, victims must be rescued and hospitalized in a short period of time, because this type of envenoming may evolve to a progressive muscle weakness and acute respiratory failure. Case Presentation We report an accident caused by Micrurus corallinus involving a 28-year-old Caucasian sailor man bitten on the hand. The accident occurred in a recreational camp because people believed the snake was not venomous. The victim presented neurological symptoms 2 h after the accident and was taken to the hospital, where he received antielapidic serum 10 h after the bite. After the antivenom treatment, the patient presented clinical evolution without complications and was discharged 4 days later. Conclusions We reinforce that it is essential to have a health care structure suitable for the treatment of snakebite. Besides, the manipulation of these animals should only be carried out by a team of well-equipped and trained professionals, and even so with special attention.

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.