Pro-inflammatory activities in elapid snake venoms

Tambourgi, Denise V.; Santos, Maria Cristina dos; Furtado, Maria de Fátima D.; Freitas, M.C.W. de; Silva, W.Dias da; Kipnis, Thereza Liberman

doi:10.1016/0041-0101(95)99313-r

Cited by 14 publications

(19 citation statements)

References 12 publications

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“…21 In addition, the CVF alters not only C system but other systems that have been implicated in evolution of ischemic brain injury, such as platelet aggregation, 22 and exhibits thrombin-like and proinflammatory activity. 23 In this work, a single-gene KO neuroprotective strategy allowed us to highlight the specific C1q-mediated mechanism of hypoxic-ischemic brain injury.…”

Section: Discussionmentioning

confidence: 99%

C1q-Deficiency Is Neuroprotective Against Hypoxic-Ischemic Brain Injury in Neonatal Mice

Ten

Sosunov

Mazer

et al. 2005

Stroke

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Background and Purpose-This study was undertaken to determine whether the initial component of the classical complement (C) activation pathway contributes to hypoxic-ischemic brain injury in neonatal mice. Methods-Hypoxia-ischemia (HI) was produced in C1qϪ/Ϫ and wild-type (WT) neonatal mice. At 24 hours after HI, neonatal mouse reflex performance and cerebral infarct volume were assessed. Long-term outcomes were measured by water-maze performance and degree of cerebral atrophy at 7 to 8 weeks after HI. Activation of circulating neutrophils, and C1q, C3, and neutrophil deposition in brains were examined. Results-C1qϪ/Ϫ mice were significantly protected against HI (meanϮSE infarct volume in C1q Ϫ/Ϫ miceϭ17.3Ϯ5.5% versus 53.6Ϯ6.8% in WT mice; PϽ0.0001) and exhibited significantly less neurofunctional deficit compared with WT mice. Immunostaining revealed significantly greater deposition of C3 (and C1q) as well as granulocytes in the infarcted brains in WT mice compared with C1q Ϫ/Ϫ animals. Activation of circulating leukocytes was significantly decreased in C1q Ϫ/Ϫ mice compared with WT mice, which correlated strongly (rϭ0.7) with cerebral infarct volumes. Conclusions-Cerebral deposition of C1q and C3 after hypoxic-ischemic insult is associated with significantly greater neurologic damage in WT mice compared with C1q Ϫ/Ϫ mice, providing strong evidence that the classical C pathway contributes to the hypoxic-ischemic brain injury. Significantly decreased activation of circulating neutrophils associated with diminished local accumulation and attenuation of brain injury in C1q Ϫ/Ϫ mice suggests a potential cellular mechanism by which C1q mediates neurodegeneration in HI.

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Section: Discussionmentioning

confidence: 99%

C1q-Deficiency Is Neuroprotective Against Hypoxic-Ischemic Brain Injury in Neonatal Mice

Ten

Sosunov

Mazer

et al. 2005

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“…22,28 Quantification of antibodies in muscle tissue by ELISA indicates that an intramuscular injection of venom drastically increases the extravasation of both IgG and F(abЈ) 2 . Therefore, it is likely that increased capillary permeability due to the inflammatory action characteristic of Micrurus venoms 29 was responsible for significant diffusion of antibodies to tissue and thus allowed for better neutralization of myotoxins if administered soon after envenomation. These results demonstrate the importance of studying the pharmacokinetics of antivenoms in envenomated animals, in addition to normal animals, to detect changes promoted by the action of venom components in the microvasculature that would affect antibody distribution.…”

Section: Discussionmentioning

confidence: 99%

Comparative study on the ability of IgG and F(ab')2 antivenoms to neutralize lethal and myotoxic effects induced by Micrurus nigrocinctus (coral snake) venom.

León¹,

Stiles²,

Alape³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. A comparative study was performed on the ability of IgG and F(abЈ) 2 antivenoms to neutralize lethal and myotoxic activities of Micrurus nigrocinctus venom. Both antivenoms were adjusted to a similar neutralizing potency in experiments where venom and antivenoms were preincubated prior to injection. No significant differences were observed between IgG and F(abЈ) 2 antivenoms concerning neutralization of lethal effect in rescue experiments, i.e., when antivenom was administered intravenously after envenomation. However, F(abЈ) 2 antivenom was more effective in prolonging the time of death when subneutralizing doses were administered immediately after venom injection. Both products partially reversed the binding of M. nigrocinctus ␣-neurotoxins to acetylcholine receptor in vitro. The IgG and F(abЈ) 2 antivenoms effectively neutralized venom-induced myotoxicity when administered intravenously immediately after envenomation, although neutralization was poor if antivenom injections were delayed. Intramuscular injection of venom promoted diffusion of antivenom antibodies throughout muscle tissue, and F(abЈ) 2 diffused to a higher extent than IgG molecules. Thus, despite the observation that F(abЈ) 2 antivenom was more effective than IgG antivenom in prolonging the time of death when subneutralizing doses were administered immediately after envenomation, no major differences were observed in antivenom neutralization of lethal and myotoxic effects or in their capacity to reverse neurotoxin binding to the acetylcholine receptor.Antivenoms constitute the mainstay for treating snakebites 1 and many antivenoms are currently produced around the world. 2,3 The majority of these products are made of F(abЈ) 2 antibody fragments resulting from pepsin digestion of equine immunoglobulins, 4 although some manufacturers produce whole IgG antivenoms. 5 Pharmacokinetic studies show that F(abЈ) 2 fragments have a more convenient profile than whole IgG preparations since they have larger volumes of distribution and reach the tissue compartment at a faster rate. 6,7 Thus, it has been assumed that F(abЈ) 2 antivenoms are more effective than IgG products in reaching and neutralizing toxins within tissues. However, León and others 8 described that IgG and F(abЈ) 2 polyvalent antivenoms do not differ in their ability to neutralize local hemorrhage, edema, and myonecrosis induced by the venom of the crotaline snake Bothrops asper. It is therefore important to test this assumption in a variety of venom-antivenom systems.Coral snakes (genus Micrurus) are the representatives of the family Elapidae in America, 9 inflicting a number of accidents on this continent. [10][11][12] Although poorly studied, Micrurus venoms induce typical neurotoxic effects, with blockade of the neuromuscular synapse by ␣-neurotoxins that bind cholinergic receptors at the motor endplate. 13-15 Micrurus ␣-neurotoxins are similar to those of other elapids. 14,15 They are low molecular weight proteins that rapidly spread throughout tissues and bind acetylcholine r...

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“…The snake venom serum proteases through their fibrinogen-converting activities (2), blood clotting factor V and protein C-activating enzymes (4-6), and C3-converting enzymes (10) are probably the most important mediator inducers of the tissue damage and symptoms provoked by Bothrops venoms.…”

Section: Discussionmentioning

confidence: 99%

“…The snake venom serine proteinase family includes enzymes that transform mammalian fibrinogen into fibrin fibers (1-3), activate clotting factor V (4,5) and plasma protein C (6,7), release kinins from kallikreinogen (8,9) and cleave the complement C3 component (10).…”

Section: Introductionmentioning

confidence: 99%

Two related thrombin-like enzymes present in Bothrops atrox venom

Petretski

Kanashiro

Silva

et al. 2000

Braz J Med Biol Res

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This article describes the presence of two new forms of a thrombinlike enzyme, both with apparent molecular masses of 38 kDa, in Bothrops atrox venom. Both share the ability to cleave fibrinogen into fibrin and to digest casein. Both present identical K m on the substrate BApNA. Their N-terminal amino acid sequences are identical for 26 residues, sharing 80% homology with batroxobin and flavoxobin. Two groups of monoclonal antibodies (mAbs) raised against the purified enzyme forms recognized different epitopes of the putative corresponding enzymes present in B. atrox crude venom. On Western blotting analysis of B. atrox crude venom, mAbs 5DB2C8, 5AA10 and 5CF11, but not mAbs 6CC5 and 6AD2-G5, revealed two or more protein bands ranging from 25 to 38 kDa. By immunoprecipitation assays, the 6AD2-G5 mAb was able to precipitate protein bands of [36][37][38] B. leucurus, B. pradoi, B. moojeni, B. jararaca and B. neuwiedii crude venoms. Fibrinogen-clotting activity was inhibited when the same venom specimens were pre-incubated with mAb 6AD2-G5, except for B. jararaca and B. neuwiedii. Correspondence

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Pro-inflammatory activities in elapid snake venoms

Cited by 14 publications

References 12 publications

C1q-Deficiency Is Neuroprotective Against Hypoxic-Ischemic Brain Injury in Neonatal Mice

C1q-Deficiency Is Neuroprotective Against Hypoxic-Ischemic Brain Injury in Neonatal Mice

Comparative study on the ability of IgG and F(ab')2 antivenoms to neutralize lethal and myotoxic effects induced by Micrurus nigrocinctus (coral snake) venom.

Two related thrombin-like enzymes present in Bothrops atrox venom

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