Myotoxicity and nephrotoxicity by Micrurus venoms in experimental envenomation (original) (raw)
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Toxicon, 2011
The coral snake Micrurus tener tener (Mtt) from the Elapidae family inhabits the southwestern United States and produces severe cases of envenomations. Although the majority of Mtt venom components are neurotoxins and phospholipase A 2 s, this study demonstrated, by SDS-PAGE and molecular exclusion chromatography (MEC), that these venoms also contain high-molecularweight proteins between 50 and 150 kDa that target the hemostatic system. The biological aspects of other Micrurus venoms were also studied, such as the LD 50 s of Micrurus isozonus (from 0.52 to 0.61 mg/kg). A pool from these venoms presented a LD 50 of 0.57 mg/kg, Micrurus f. fulvius (Mff) and Mtt had LD 50 s of 0.32 and 0.78 mg/kg, respectively. These venoms contained fibrino(geno)lytic activity, they inhibited platelet aggregation, as well as factor Xa and/or plasminlike activities. M. isozonus venoms from different Venezuelan geographical regions inhibited ADP-induced platelet aggregation (from 50 to 68%). Micrurus tener tener venom from the United States was the most active with a 95.2% inhibitory effect. This venom showed thrombin-like activity on fibrinogen and human plasma. Fractions of Mtt showed fibrino(geno)lytic activity and inhibition on plasmin amidolytic activity. Several fractions degraded the fibrinogen Aα chains, and fractions F2 and F7 completely degraded both fibrinogen Aα and Bβ chains. To our knowledge, this is the first report on thrombin-like and fibrino(geno)lytic activity and plasmin or factor Xa inhibitors described in Micrurus venoms. Further purification and characterization of these Micrurus venom components could be of therapeutic use in the treatment of hemostatic disorders.
Biological and enzymatic activities of Micrurus sp. (Coral) snake venoms
Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2005
The venoms of Micrurus lemniscatus carvalhoi, Micrurus frontalis frontalis, Micrurus surinamensis surinamensis and Micrurus nigrocinctus nigrocinctus were assayed for biological activities. Although showing similar liposome disrupting and myotoxic activities, M. frontalis frontalis and M. nigrocinctus nigrocinctus displayed higher anticoagulant and phospholipase A 2 (PLA 2 ) activities. The latter induced a higher edema response within 30 min. Both venoms were the most toxic as well. In the isolated chick biventer cervicis preparation, M. lemniscatus carvalhoi venom blocked the indirectly elicited twitch-tension response (85F0.6% inhibition after a 15 min incubation at 5 Ag of venom/mL) and the response to acetylcholine (ACh; 55 or 110 AM), without affecting the response to KCl (13.4 mM). In mouse phrenic nerve-diaphragm preparation, the venom (5 Ag/mL) produced a complete inhibition of the indirectly elicited contractile response after 50 min incubation and did not affect the contractions elicited by direct stimulation. M. lemniscatus carvalhoi inhibited 3 H-l-glutamate uptake in brain synaptosomes in a Ca 2+ , but not time, dependent manner. The replacement of Ca 2+ by Sr 2+ and ethylene glycol-bis(h-aminoethyl ether) (EGTA), or alkylation of the venom with p-bromophenacyl bromide (BPB), inhibited 3 H-l-glutamate uptake. M. lemniscatus carvalhoi venom cross-reacted with postsynaptic a-neurotoxins short-chain (antineurotoxin-II) and long-chain (antibungarotoxin) antibodies. It also cross-reacted with antimyotoxic PLA 2 antibodies from M. nigrocinctus nigrocinctus (antinigroxin). Our results point to the need of catalytic activity for these venoms to exert their neurotoxic activity efficiently and to their components as attractive tools for the study of molecular targets on cell membranes.
Journal of venom research, 2011
The neuromuscular activity of Micrurus pyrrochryptus venom was studied in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. The venom (0.5-50μg/ml) caused irreversible, time-and concentration-dependent blockade, with BC being more sensitive than PND (50% blockade with 10μg/ ml in 22±3min and 62±4min, respectively; mean±SEM, n=6; p<0.05). In BC preparations, venom (0.5μg/ ml) progressively abolished ACh-induced contractures, whereas contractures to exogenous KCl and muscle twitches in curarized preparations were unaffected. The venom neither altered creatine kinase release (venom: 25.8±1.75IU/l vs control: 24.3±2.2IU/l, n=6, after 120min), nor it caused significant muscle damage (50μg of venom/ml vs control: 3.5±0.8% vs 1.1±0.7% for PND; 4.3±1.5% vs 1.2±0.5% for BC, n=5). The venom had low PLA 2 activity. Neurotoxicity was effectively neutralized by commercial Micrurus antivenom and specific antivenom. These findings indicate that M. pyrrhocryptus venom acts postsynaptically on nicotinic receptors, with no significant myotoxicity.
PLoS Neglected Tropical Diseases, 2010
Background: Micrurus snake bites can cause death by muscle paralysis and respiratory arrest, few hours after envenomation. The specific treatment for coral snake envenomation is the intravenous application of heterologous antivenom and, in Brazil, it is produced by horse immunization with a mixture of M. corallinus and M. frontalis venoms, snakes that inhabit the South and Southeastern regions of the country. However, this antivenom might be inefficient, considering the existence of intra-and inter-specific variations in the composition of the venoms. Therefore, the aim of the present study was to investigate the toxic properties of venoms from nine species of Micrurus: eight present in different geographic regions of Brazil (M. frontalis, M. corallinus, M. hemprichii, M. spixii, M. altirostris, M. surinamensis, M. ibiboboca, M. lemniscatus) and one (M. fulvius) with large distribution in Southeastern United States and Mexico. This study also analyzed the antigenic crossreactivity and the neutralizing potential of the Brazilian coral snake antivenom against these Micrurus venoms.
The biological properties of venoms of some american coral snakes (Genus Micrurus
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 1992
1. The biological properties of nine venom samples from six taxa of Micrurus were investigated. The venoms exhibited low protease, phosphodiesterase and 5'-nucleotidase activities, moderate to strong phospholipase A and hyaluronidase activities, variable I.-amino acid oxidase activity and were devoid of arginine ester hydrolase and thrombin-like activities. Some venom samples exhibited strong acetylcholinesterase activity. Venoms of M. c. dumerili and M. frontalis exhibited exceptionally high alkaline phosphomonoesterase activity while two of the M. f fulvius venom samples tested exhibited strong hemorrhagic activity in mice.
Toxicon, 1994
A. ALAPE-GIRtSN, B. GUSTAFSSON, B. LOMONTE, M. THELESTAM and J. M. GUTIf?R-REZ. lamlunochemical characterization of Micrurus nigrocinctus nigrocinctus venom with monoclonal and polyclonal antibodies. Toxicon 32, 695-712, 1994.-Eleven marine monocloncal antibodies (MAbs) against Micrurus nigrocinctus nigrocinctus venom were produced and partially characterized . When M. n. nigrocinctus venom proteins were separated by SDS-PAGE under non-reducing conditions four sharp and three diffuse bands were observed. The sharp bands had migration rates comparable to reduced standards of 10, 12, 50 and 72 kDa. The diffuse bands migrate in the range of reduced standards from 14.5 to 32 kDa. When venom proteins were separated under reducing conditions the same sharp bands and an additional prominent 14.5 kDa band were observed . Three antibodies (MAbs 4, 21 and 28) recognized the diffuse bands in western blots of non-reducing SDS-PAGE, whereas MAbs 7G, 22 and 26 reacted with only the 72 kDa protein . MAbs 21 and 28 reacted with the 14.5 kDa band whereas MAb 7G recognized the 72 kDa band in blots ofreducing SDS-PAGE.
Toxicon : official journal of the International Society on Toxinology, 2018
Micrurus venoms are known to induce mainly neurotoxicity in victims. However, other manifestations, including hemorrhage, edema, myotoxicity, complement activation, and hemostatic activity have been reported. In order to develop a more complete pharmacological profile of these venoms, inflammatory responses and hemostasis were evaluated in C57BL/6 mice treated with a sub-lethal dose of M. t. tener (Mtt) venom (8 μg/mouse), inoculated intraperitoneally. The venom induced moderate bleeding into the abdominal cavity and lungs, as well as infiltration of leukocytes into the liver. After 30 min, the release of pro-inflammatory mediators (TNF-α, IL-6, and NO) were observed, being most evident at 4 h. There was a decrease in hemoglobin and hematocrit levels at 72 h, a prolongation in coagulation times (PT and aPTT), a decrease in the fibrinogen concentration and an increase in fibrinolytic activity. In this animal model, it was proposed that Mtt venom induces inflammation with the release ...