Low-level laser therapy decreases local effects induced by myotoxins isolated from Bothrops jararacussu snake venom

The prominent myotoxic effects induced by Bothrops jararacussu crude venom are due, in part, to its polycationic myotoxins, BthTX-I and BthTX-II. Both myotoxins have a phospholipase A2 structure: BthTX-II is an active enzyme Asp-49 PLA2, while BthTX-I is a Lys-49 PLA2 devoid of enzymatic activity. In this study, the effect of low-level laser therapy (LLLT), 685 nm laser at a dose of 4.2 J/cm2 on edema formation, leukocyte influx and myonecrosis caused by BthTX-I and BthTX-II, isolated from Bothrops jararacussu snake venom, was analyzed. BthTX-I and BthTX-II caused a significant edema formation, a prominent leukocyte infiltrate composed predominantly by neutrophils and myonecrosis in envenomed gastrocnemius muscle. LLLT significantly reduced the edema formation, neutrophil accumulation and myonecrosis induced by both myotoxins 24 hours after the injection. LLLT reduced the myonecrosis caused by BthTX-I and BthTX-II, respectively, by 60 and 43%; the edema formation, by 41 and 60.7%; and the leukocyte influx, by 57.5 and 51.6%. In conclusion, LLLT significantly reduced the effect of these snake toxins on the inflammatory response and myonecrosis. These results suggest that LLLT should be considered a potential therapeutic approach for treatment of local effects of Bothrops species venom.Fundação Vale Paraibana de Ensin

Anti-inflammatory activity of Blutaparon portulacoides ethanolic extract against the inflammatory reaction induced by Bothrops jararacussu venom and isolated myotoxins BthTX-I and II

This article reports the anti-inflammatory effect of Blutaparon portulacoides (B. portulacoides), specifically the ethanolic extract of its aerial parts, on the edema formation and leukocyte influx caused by Bothrops jararacussu (B. jararacussu) snake venom and Bothropstoxin-I and II (BthTX-I and II) isolated from this venom as an alternative treatment for Bothrops snakebites. The anti-inflammatory effect of B. portulacoides ethanolic extract was compared with an animal group pretreated with dexamethasone. B. portulacoides ethanolic extract significantly inhibited paw edema induced by B. jararacussu venom and by BthTX-I and II. Also, results demonstrated that the extract caused a reduction of the leukocyte influx induced by BthTX-I. However, the extract was not capable of inhibiting the leukocyte influx induced by the venom and by BthTX-II. In conclusion, these results suggest that the ethanolic extract of this plant possess components able to inhibit or inactivate toxins present in B. jararacussu venom, including its myotoxins, responsible for the edema formation. However, the leukocyte migration caused by the venom and BthTX-II was not inhibited by the plant, probably due to the different mechanisms involved in the edema formation and leukocyte influx. This is the first report of B. portulacoides extract as anti-inflammatory against snake venoms and isolated toxins

Acute hepatotoxicity of Crotalus durissus terrificus (South American rattlesnake) venom in rats

Venom of the South American rattlesnake, Crotalus durissus terrificus (Cdt), presents myotoxic and neurotoxic outcomes, but reports on its effects on the liver are scarce. This study examined the hepatotoxicity resulting from Cdt venom administration (100, 200 and 300 µg/kg) in male Wistar rats. Animals were studies at 3, 6, 9 and 12 hours after venom injection. The hepatotoxicity was assessed through serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma glutamyl transferase (GGT), bilirrubin and also by histopathological evaluation. All the different concentrations of Cdt venom resulted in increased levels of hepatic enzymes, when compared with the control group, except for the 100 µg/kg dose, which presented normal levels at 9 and 12 hours after venom administration. Bilirrubin levels remained unchanged by Cdt venom. Histological analysis revealed endothelial damage, inflammatory cell infiltration, as well as sinusoidal and portal congestion. Based on these observations, we may conclude that Cdt venom causes dose- and time-dependent hepatic damage in rats, characterized by elevated hepatic enzyme levels and histological alterations

ACUTE HEPATOTOXICITY OF Crotalus durissus terrificus (SOUTH AMERICAN RATTLESNAKE) VENOM IN RATS

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Venom of the South American rattlesnake, Crotalus durissus terrificus (Cdt), presents myotoxic and neurotoxic outcomes, but reports on its effects on the liver are scarce. This study examined the hepatotoxicity resulting from Cdt venom administration (100, 200 and 300 mu g/kg) in male Wistar rats. Animals were studies at 3, 6, 9 and 12 hours after venom injection. The hepatotoxicity was assessed through serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma glutamyl transferase (GGT), bilirrubin and also by histopathological evaluation. All the different concentrations of Cdt venom resulted in increased levels of hepatic enzymes, when compared with the control group, except for the 100 mu g/kg dose, which presented normal levels at 9 and 12 hours after venom administration. Bilirrubin levels remained unchanged by Cdt venom. Histological analysis revealed endothelial damage, inflammatory cell infiltration, as well as sinusoidal and portal congestion. Based on these observations, we may conclude that Cdt venom causes dose- and time-dependent hepatic damage in rats, characterized by elevated hepatic enzyme levels and histological alterations.1516178Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FVE/UNIVAPFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Envenomations by Bothrops and Crotalus Snakes Induce the Release of Mitochondrial Alarmins

Skeletal muscle necrosis is a common manifestation of viperid snakebite envenomations. Venoms from snakes of the genus Bothrops, such as that of B. asper, induce muscle tissue damage at the site of venom injection, provoking severe local pathology which often results in permanent sequelae. In contrast, the venom of the South American rattlesnake Crotalus durissus terrificus, induces a clinical picture of systemic myotoxicity, i.e., rhabdomyolysis, together with neurotoxicity. It is known that molecules released from damaged muscle might act as ‘danger’ signals. These are known as ‘alarmins’, and contribute to the inflammatory reaction by activating the innate immune system. Here we show that the venoms of B. asper and C. d. terrificus release the mitochondrial markers mtDNA (from the matrix) and cytochrome c (Cyt c) from the intermembrane space, from ex vivo mouse tibialis anterior muscles. Cyt c was released to a similar extent by the two venoms whereas B. asper venom induced the release of higher amounts of mtDNA, thus reflecting hitherto some differences in their pathological action on muscle mitochondria. At variance, injection of these venoms in mice resulted in a different time-course of mtDNA release, with B. asper venom inducing an early onset increment in plasma levels and C. d. terrificus venom provoking a delayed release. We suggest that the release of mitochondrial ‘alarmins’ might contribute to the local and systemic inflammatory events characteristic of snakebite envenomations

ANTI-INFLAMMATORY ACTIVITY OF Blutaparon portulacoides ETHANOLIC EXTRACT AGAINST THE INFLAMMATORY REACTION INDUCED BY Bothrops jararacussu VENOM AND ISOLATED MYOTOXINS BthTX-I AND II

This article reports the anti-inflammatory effect of Blutaparon portulacoides (B. portulacoides), specifically the ethanolic extract of its aerial parts, on the edema formation and leukocyte influx caused by Bothrops jararacussu (B. jararacussu) snake venom and Bothropstoxin-I and II (BthTX-I and II) isolated from this venom as an alternative treatment for Bothrops snakebites. The anti-inflammatory effect of B. portulacoides ethanolic extract was compared with an animal group pretreated with dexamethasone. B. portulacoides ethanolic extract significantly inhibited paw edema induced by B. jararacussu venom and by BthTX-I and II. Also, results demonstrated that the extract caused a reduction of the leukocyte influx induced by BthTX-I. However, the extract was not capable of inhibiting the leukocyte influx induced by the venom and by BthTX-II. In conclusion, these results suggest that the ethanolic extract of this plant possess components able to inhibit or inactivate toxins present in B. jararacussu venom, including its myotoxins, responsible for the edema formation. However, the leukocyte migration caused by the venom and BthTX-II was not inhibited by the plant, probably due to the different mechanisms involved in the edema formation and leukocyte influx. This is the first report of B. portulacoides extract as anti-inflammatory against snake venoms and isolated toxins.15352754

Comparison of the neurotoxic and myotoxic effects of Brazilian Bothrops venoms and their neutralization by commercial antivenom

The venoms of some Bothrops species produce neuromuscular blockade in avian and mammalian nerve-muscle preparations in vitro. In this study, we compared the neuromuscular activities (myotoxicity and neurotoxicity) of venoms from several Brazilian species of Bothrops (B. jararaca, B. jararacussu, B. moojeni, B. erythromelas and B. neuwiedi) in chick isolated biventer cervicis muscle preparations and examined their neutralization by commercial antivenom. All of the venoms (50-200 mug/ml, n = 3-7 each) induced long-lasting, concentration-dependent muscle contracture and twitch-tension blockade, and also inhibited the muscle responses to acetylcholine and KCl. Preincubation of the venoms (200 mug/ml) with bothropic antivenom (0.2 ml) for 30 min at 37 degreesC prevented the twitch-tension blockade to different extents, with the protection varying from 0.5% (B. neuwiedi) to 88% (B. moojeni). Complete protection against the neuromuscular action of B. neuwiedi venom was observed only with a mixture of bothropic and crotalic antivenoms. The venoms caused either high (B. jararacussu, B. neuwiedi and B. moojeni) or low (B. jararaca and B. erythromelas) creatine kinase release. Morphologically, myonecrosis was greatest with B. jararacussu venom (98-100% of fibers damaged) and least with B. jararaca venom (74% damage). The extent of neutralization by bothropic antivenom was B. jararaca (93%) > B. erythromelas (65.8%) > B. moojeni (30.7%) > B. neuwiedi (20%) > B. jararacussu (no neutralization). Despite this variation in neutralization, enzyme-linked immunosorbent assays indicated similar immunoreactivities for the venoms, although immunoblots revealed quantitative variations in the bands detected. These results show that Bothrops venoms produce varying degrees of neuromuscular blockade in chick nerve-muscle preparations. The variable protection by antivenom against neuromuscular activity indicates that the components responsible for the neuromuscular action may differ among the venoms. (C) 2004 Elsevier Ltd. All rights reserved.44325927

Effect of Low-Level Laser Therapy in the Myonecrosis Induced by Bothrops jararacussu Snake Venom

Objective: The aim of this work was to investigate the capacity of low-level laser therapy (LLLT) alone or in combination with antivenom (AV) to reduce myonecrosis induced by Bothrops jararacussu snake venom. Background Data: Myonecrosis is the most pronounced local effect caused by B. jararacussu venom. AV therapy and other first-aid treatments do not reverse these local effects. Material and Methods: Male Swiss mice were used. Myonecrosis was induced by injection of 0.6mg/kg of B. jararacussu venom in the right gastrocnemius muscle and was evaluated at 3 or 24 h after venom injection. The site of venom administration was irradiated for 29s with a low power semiconductor laser (685 nm) at a dose of 4.2 J/cm(2). Intravenous AV therapy (0.5 mL dose) was administered at different times: 30 min before venom injection or 0, 1, or 3 h afterward. Both AV therapy and LLLT treatments were duplicated in mice groups killed at 3 or 24 h. Results: B. jararacussu venom caused a significant myonecrotic effect 3 and 24 h after venom injection. LLLT significantly reduced myonecrosis by 83.5% at 24h (p < 0.05) but not at 3 h, and AV therapy alone was ineffective for reducing myonecrosis at 3 and 24 h. Conclusion: Only LLLT significantly reduced myonecrosis of the envenomed muscle, suggesting that LLLT is a potentially therapeutic approach for treating the local effects of B. jararacussu venom.o TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.274591597Fundacao Vale Paraibana de Ensino (FVE

Anti-Inflammatory Effect of Low-Level Laser and Light-Emitting Diode in Zymosan-Induced Arthritis

Objective: The aim of this work was to investigate the effect of low-level laser therapy (LLLT) and light-emitting diode (LED) on formation of edema, increase in vascular permeability, and articular joint hyperalgesia in zymosan-induced arthritis. Background Data: It has been suggested that low-level laser and LED irradiation can modulate inflammatory processes. Material and Methods: Arthritis was induced in male Wistar rats (250-280 g) by intra-articular injection of zymosan (1 mg in 50 mu L of a sterile saline solution) into one rear knee joint. Animals were irradiated immediately, 1 h, and 2 h after zymosan administration with a semiconductor laser (685 nm and 830 nm) and an LED at 628 nm, with the same dose (2.5 J/cm(2)) for laser and LED. In the positive control group, animals were injected with the anti-inflammatory drug dexamethasone 1 h prior to the zymosan administration. Edema was measured by the wet/dry weight difference of the articular tissue, the increase in vascular permeability was assessed by the extravasation of Evans blue dye, and joint hyperalgesia was measured using the rat knee-joint articular incapacitation test. Results: Irradiation with 685 nm and 830 nm laser wavelengths significantly inhibited edema formation, vascular permeability, and hyperalgesia. Laser irradiation, averaged over the two wavelengths, reduced the vascular permeability by 24%, edema formation by 23%, and articular incapacitation by 59%. Treatment with LED (628 nm), with the same fluence as the laser, had no effect in zymosan-induced arthritis. Conclusion: LLLT reduces inflammatory signs more effectively than LED irradiation with similar irradiation times (100 sec), average outputs (20 mW), and energy doses (2 J) in an animal model of zymosan-induced arthritis. The anti-inflammatory effects of LLLT appear to be a class effect, which is not wavelength specific in the red and infrared parts of the optical spectrum.o TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.28222723