The effect of treatment with crotapotin on the evolution of experimental autoimmune neuritis induced in Lewis rats

Castro, Fabiano R.; Farias, Alessandro S.; Proença, Patricia L.F.; Hoz, Cristiane de la; Langone, Francesco; Oliveira, E. Capelas de; Toyama, Marcos H.; Marangoni, Sérgio; Santos, Leonilda M.B.

doi:10.1016/j.toxicon.2006.09.028

Cited by 22 publications

(16 citation statements)

References 23 publications

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“…Similar to that observed in our model, a protective effect of the crotapotin (CA), a CTX subunit, was reported in experimental models of autoimmune encephalomyelitis and neuritis resulting in a lower clinical score for these diseases [ 65 , 66 ]. Other studies demonstrated that the CB, from CTX, exerts an anti-inflammatory effect in some experimental models [ 67 , 68 ].…”

Section: Discussionsupporting

confidence: 87%

Crotoxin from Crotalus durissus terrificus Is Able to Down-Modulate the Acute Intestinal Inflammation in Mice

et al. 2015

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Inflammatory bowel diseases (IBD) is the result of dysregulation of mucosal innate and adaptive immune responses. Factors such as genetic, microbial and environmental are involved in the development of these disorders. Accordingly, animal models that mimic human diseases are tools for the understanding the immunological processes of the IBD as well as to evaluate new therapeutic strategies. Crotoxin (CTX) is the main component of Crotalus durissus terrificus snake venom and has an immunomodulatory effect. Thus, we aimed to evaluate the modulatory effect of CTX in a murine model of colitis induced by 2,4,6- trinitrobenzene sulfonic acid (TNBS). The CTX was administered intraperitoneally 18 hours after the TNBS intrarectal instillation in BALB/c mice. The CTX administration resulted in decreased weight loss, disease activity index (DAI), macroscopic tissue damage, histopathological score and myeloperoxidase (MPO) activity analyzed after 4 days of acute TNBS colitis. Furthermore, the levels of TNF-α, IL-1β and IL-6 were lower in colon tissue homogenates of TNBS-mice that received the CTX when compared with untreated TNBS mice. The analysis of distinct cell populations obtained from the intestinal lamina propria showed that CTX reduced the number of group 3 innate lymphoid cells (ILC3) and Th17 population; CTX decreased IL-17 secretion but did not alter the frequency of CD4+Tbet+ T cells induced by TNBS instillation in mice. In contrast, increased CD4+FoxP3+ cell population as well as secretion of TGF-β, prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) was observed in TNBS-colitis mice treated with CTX compared with untreated TNBS-colitis mice. In conclusion, the CTX is able to modulate the intestinal acute inflammatory response induced by TNBS, resulting in the improvement of clinical status of the mice. This effect of CTX is complex and involves the suppression of the pro-inflammatory environment elicited by intrarectal instillation of TNBS due to the induction of a local anti-inflammatory profile in mice.

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Section: Discussionsupporting

confidence: 87%

Crotoxin from Crotalus durissus terrificus Is Able to Down-Modulate the Acute Intestinal Inflammation in Mice

et al. 2015

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“…Crotoxin (CTX) is the main toxin responsible for the high toxicity of this venom [14]. In low doses, CTX presents immunomodulatory, anti-inflammatory, antitumor, and antinociceptive effects [13,[15][16][17][18]. Regarding antinociception, studies have shown that CTX can inhibit both acute [19,20] and chronic pain when topically applied at the site of the nerve injury [16]; this effect is mediated by central muscarinic receptors, α-adrenergic receptors, serotonergic and noradrenergic systems [16,19].…”

Section: Introductionmentioning

confidence: 99%

Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice

Sant’Anna

Lopes

Kimura

et al. 2019

Toxins

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Neuropathic pain is a disease caused by structural and functional plasticity in central and peripheral sensory pathways that produce alterations in nociceptive processing. Currently, pharmacological treatment for this condition remains a challenge. Crotoxin (CTX), the main neurotoxin of Crotalus durissus terrificus rattlesnake venom, has well described prolonged anti-inflammatory and antinociceptive activities. In spite of its potential benefits, the toxicity of CTX remains a limiting factor for its use. SBA-15 is an inert nanostructured mesoporous silica that, when used as a vehicle, may reduce toxicity and potentiate the activity of different compounds. Based on this, we propose to conjugate crotoxin with SBA-15 (CTX:SBA-15) in order to investigate if when adsorbed to silica, CTX would have its toxicity reduced and its analgesic effect enhanced in neuropathic pain induced by the partial sciatic nerve ligation (PSNL) model. SBA-15 enabled an increase of 35% of CTX dosage. Treatment with CTX:SBA-15 induced a long-lasting reduction of mechanical hypernociception, without modifying the previously known pathways involved in antinociception. Moreover, CTX:SBA-15 reduced IL-6 and increased IL-10 levels in the spinal cord. Surprisingly, the antinociceptive effect of CTX:SBA-15 was also observed after oral administration. These data indicate the potential use of the CTX:SBA-15 complex for neuropathic pain control and corroborates the protective potential of SBA-15.

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“…Indeed, the immunosuppressive effect of venom and crotoxin (a toxin isolated from Crotalus durissus terrificus) was reported [68]. Crotapotin, an acidic and non-toxic subunit of crotoxin, administrated by intraperitoneal route, significantly reduces the severity of experimental autoimmune neuritis, an experimental model for Guillain-Barré syndrome, which indicate a novel path for neuronal protection in this autoimmune disease and other inflammatory demyelinating neuropathies [69]. Inappropriate activation of complement system occurs in a large number of inflammatory, ischaemic and other diseases.…”

Section: Toxins Acting On Immunological Systemmentioning

confidence: 99%

Toxins from Venomous Animals: Gene Cloning, Protein Expression and Biotechnological Applications

Fernandes-Pedrosa¹,

Félix-Silva²,

Menezes³

2013

An Integrated View of the Molecular Recognition and Toxinology - From Analytical Procedures to Biomedical Applications

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and binding site on different channels or channel subtypes. The venom is constituted by mucopolysaccharides, hyaluronidases, phospholipases, serotonins, histamines, enzyme inhibitors, antimicrobials and proteins namely neurotoxic peptides. Scorpion peptides presents specificity and high affinity and have been used as pharmacological tools to characterize various receptor proteins involved in normal ion channel functionating, as abnormal channel functionating in cases of diseases. The venoms can be characterized by identification of peptide toxins analysis of the structure of the toxins and also have proven to be among the most and selective antagonists available for voltage-gated channels permeable to K + , Na + , and Ca 2+. The neurotoxic peptides and small proteins lead to dysfunction and provoke pathophysiological actions, such as membrane destabilization, blocking of the central, and peripheral nervous systems or alteration of smooth or skeletal muscle activity [5-8]. Spider venoms are complex mixtures of biologically active compounds of different chemical nature, from salts to peptides and proteins. Specificity of action of some spider toxins is unique along with high toxicity for insects, they can be absolutely harmless for members of other taxons, and this could be essential for investigation of insecticides. Several spider toxins have been identified and characterized biochemically. These include mainly ribonucleotide phosphohydrolase, hyaluronidases, serine proteases, metalloproteases, insecticidal peptides and phospholipases D [9-10]. Venoms from toads and frogs have been extensively isolated and characterized showing molecules endowed with antimicrobial and/or cytotoxic activities [11]. Studies involving the molecular repertoire of the venom of bees and wasps have revealed the partial isolation, characterization and biological activity assays of histamines, dopamines, kinins, phospholipases and hyaluronidases. The venom of caterpillars has been partially characterized and contains mainly ester hydrolases, phospholipases and proteases [12]. The purpose of this chapter is to present the main toxins isolated and characterized from the venom of venomous animals, focusing on their biotechnological and pharmacological applications. 2. Biotechnological and pharmacological applications of snake venom toxins While the initial interest in snake venom research was to understand how to combat effects of snakebites in humans and to elucidate toxins mechanisms, snake venoms have become a fertile area for the discovery of novel products with biotechnological and/or pharmacological applications [13-14]. Since then, many different products have been developed based on purified toxins from snake venoms, as well recent studies have been showing new potential molecules for a variety of applications [15]. 2.1. Toxins acting on cardiovascular system Increase in blood pressure is often a transient physiological response to stressful stimuli, which allows the body to react to dangers or to promptly increase activity. However,...

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The effect of treatment with crotapotin on the evolution of experimental autoimmune neuritis induced in Lewis rats

Cited by 22 publications

References 23 publications

Crotoxin from Crotalus durissus terrificus Is Able to Down-Modulate the Acute Intestinal Inflammation in Mice

Crotoxin from Crotalus durissus terrificus Is Able to Down-Modulate the Acute Intestinal Inflammation in Mice

Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice

Toxins from Venomous Animals: Gene Cloning, Protein Expression and Biotechnological Applications

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