Serotherapy against Voltage-Gated Sodium Channel-Targeting α-Toxins from Androctonus Scorpion Venom

Martin‐Eauclaire, Marie‐France; Adi-Bessalem, Sonia; Hammoudi-Triki, Djelila; Laraba-Djebari, Fatima; Bougis, Pierre E.

doi:10.3390/toxins11020063

Cited by 15 publications

(7 citation statements)

References 128 publications

(172 reference statements)

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“…Then, we predicted that S12 and L14 played a key role in binding VSD2 rNav1.8 with Syb-prII-1. Meanwhile, Lys104 was the main contributor to the interaction, which was consistent with the previous finding [25]. Table 1.…”

Section: The Results Of Molecular Dynamics Simulationsupporting

confidence: 91%

Scorpion Neurotoxin Syb-prII-1 Exerts Analgesic Effect through Nav1.8 Channel and MAPKs Pathway

Bai

Song

Cao

et al. 2022

IJMS

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Trigeminal neuralgia (TN) is a common type of peripheral neuralgia in clinical practice, which is usually difficult to cure. Common analgesic drugs are difficult for achieving the desired analgesic effect. Syb-prII-1 is a β-type scorpion neurotoxin isolated from the scorpion venom of Buthus martensi Karsch (BmK). It has an important influence on the voltage-gated sodium channel (VGSCs), especially closely related to Nav1.8 and Nav1.9. To explore whether Syb-prII-1 has a good analgesic effect on TN, we established the Sprague Dawley (SD) rats’ chronic constriction injury of the infraorbital nerve (IoN-CCI) model. Behavioral, electrophysiological, Western blot, and other methods were used to verify the model. It was found that Syb-prII-1 could significantly relieve the pain behavior of IoN-CCI rats. After Syb-prII-1 was given, the phosphorylation level of the mitogen-activated protein kinases (MAPKs) pathway showed a dose-dependent decrease after IoN-CCI injury. Moreover, Syb-prII-1(4.0 mg/kg) could significantly change the steady-state activation and inactivation curves of Nav1.8. The steady-state activation and inactivation curves of Nav1.9 were similar to those of Nav1.8, but there was no significant difference. It was speculated that it might play an auxiliary role. The binding mode, critical residues, and specific interaction type of Syb-prII-1 and VSD2rNav1.8 were clarified with computational simulation methods. Our results indicated that Syb-prII-1 could provide a potential treatment for TN by acting on the Nav1.8 target.

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Section: The Results Of Molecular Dynamics Simulationsupporting

confidence: 91%

Scorpion Neurotoxin Syb-prII-1 Exerts Analgesic Effect through Nav1.8 Channel and MAPKs Pathway

Bai

Song

Cao

et al. 2022

IJMS

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“…This antibody fragment specific for Ts1 toxin from T. serrulatus also recognized toxins from the scorpions T. packyurus and T. obscurus from the Amazonian region [ 137 ]. The design of efficient serotherapies is challenged by the structural and antigenic polymorphisms reported in the α-toxin family [ 138 ]. For instance, T. obscurus and T. serrulatus venoms have toxins with distinct epitopes for the same protein classes [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

Scorpion species of medical importance in the Brazilian Amazon: a review to identify knowledge gaps

Martins¹,

Santos

Procópio

et al. 2021

J. Venom. Anim. Toxins incl. Trop. Dis

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Scorpionism is a relevant medical condition in Brazil. It is responsible for most accidents involving venomous animals in the country, which leads to severe symptoms that can evolve to death. In recent years, an increase of almost 50% in the incidence of scorpionism has been observed in the Northern Region, where the highest severity of envenoming has been notified since the beginning of the 21 st century. This review aims to provide an in-depth assessment of public data and reports on symptoms and epidemiology of envenoming, ecological aspects of scorpions, and characterization of venoms and toxins to access the gaps that need to be filled in the knowledge of the scorpion species of medical importance from the Brazilian Amazon. A systematic search using the string words “Amazon” and “scorpion” was performed on 11 databases. No restriction on date, language or status of the publication was applied. Reports not related to the Brazilian Amazon were excluded. Therefore, 88 studies remained. It is shown that populations of scorpions of medical importance, even of the same species, may present significant toxic variations peculiar to some regions in the Brazilian Amazon, and commercial scorpion antivenoms were not able to shorten the intensity and duration of neurological manifestations in patients stung by T. silvestris, T. apiacas or T. obscurus . It is also highlighted that the toxins responsible for triggering these alterations have not been elucidated yet and this is a fruitful field for the development of more efficient antivenoms. Furthermore, the geographic distribution of scorpions of the genus Tityus in the Brazilian Amazon was revised and updated. The cumulative and detailed information provided in this review may help physicians and scientists interested in scorpionism in the Brazilian Amazon.

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“…Nitric oxide (NO) is produced by in ltrated in ammatory cells in various organs of envenomed animals. It has been proposed that the inducible isorform (type II) of NOS, a signi cant free radical, functions as a second messenger in processes which cause cytokines-mediated circulatory shock [9].…”

Section: Introductionmentioning

confidence: 99%

“….6.2.Receiver Operating Characteristics (ROC) curve analysis of IL-1β and MDA in prediction of ECG abnormality.The IL-1β cutoff value >50.5 pg/ml can predict ECG abnormality with sensitivity of 94.12%, speci city of 50 %, PPV of 76.2% and with accuracy of 77.8% (table 6, gure 2).Regarding IL-1β, cutoff value >78.11 pg/ml can predict echo abnormality with sensitivity of 66.67%, speci city of 94.44 %, PPV of 85.7% and t with 85.2% accuracy (table 7, gure 3).Moreover, the cutoff value of MDA of 2.95 nmol/ml can predict echo abnormality with sensitivity of 55.56 %, speci city of 94.44%, PPV of 83.3 % and with 81.5 % accuracy (table 7, gure 3).There was a signi cant statistical difference between pancreatic function with IL-1β and MDA (table9). Table(9): Showing comparison between the patient pancreatic function with IL-1β and MDA.…”

mentioning

confidence: 99%

The correlation between interleukin 1β (IL-1β) as an inflammatory marker and Malondialdehyde (MDA) as a lipid peroxidation marker and the development of cardiac and pancreatic complications in humans suspected to scorpion poisoning

Mebed,

zakaria,

setouhi

et al. 2023

Preprint

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Back ground Scorpion envenomation is a common health problem all over the world. Recent experimental studies on animals were held to prove the correlation between interleukin 1 β (IL-1β), lipid peroxidation and nitric oxide (NO) production in the development of cardiac and pancreatic abnormalities after scorpion venom exposure. The aim of this study is to assess the correlation of lipid peroxidation and IL-1β release and the development of cardiac and pancreatic complications associated with scorpion envenomation in humans which will subsequently evaluate their role in prediction of cardiac or pancreatic complications and help the physicians when to determine to use antioxidants and (IL-1β) receptor blockers in treatment in addition to scorpion antivenom. Methods In this study, 88 subjects were recruited from El-Minia university hospital. All the patients admitted with scorpion envenomtion diagnosis were enrolled over a period of 12 months; from the 1st of Jan 2021 till the 30th of Jan 2022. After exclusion of 7 patients, the remaining subjects were divided into four groups of subjects according to their cardiac function into two groups: group A with normal cardiac function contained: 30 normal subjects, group B contained 51 subjects who had abnormal cardiac functions. The patients were considered to have abnormal cardiac function if they had at least one or more abnormal cardiac investigations (cardiac troponin I (c TN-I), electrocardiogram (ECG), and/or, trans thoracic echocardiography (TTE)).The same patients were divided into another two groups: group C with normal pancreatic function contained: 36 normal subjects, group D contained 45 subjects who had abnormal pancreatic function. Pancreatic function was considered abnormal if one or both of serum amylase & random blood sugar results weren’t normal. Results Our results showed the following: Regarding cardiac abnormality, there were significant statistical differences with both levels of IL-1β and MDA. Regarding pancreatic abnormality, there were insignificant statistical differences with both levels of IL-1β and MDA. Cutoff values were calculated to help health care providers to assess when to introduce such treatments in addition to antivenom to help to counteract these complications and decline the mortality rates. Conclusion It was concluded that IL-1β and MDA have significant correlations in development of cardiac and pancreatic functions abnormalities; the treatments that modify their release or counteract their action may be beneficial. Trial registration The research was approved by the ethical committee board of the faculty of medicine, Minia University, with approval number 206: December/2021. Patients or their first degree relatives (according to the conscious level) were informed by all procedures included in the study and were asked to sign informed consent if they agreed to participate in.

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Serotherapy against Voltage-Gated Sodium Channel-Targeting α-Toxins from Androctonus Scorpion Venom

Cited by 15 publications

References 128 publications

Scorpion Neurotoxin Syb-prII-1 Exerts Analgesic Effect through Nav1.8 Channel and MAPKs Pathway

Scorpion Neurotoxin Syb-prII-1 Exerts Analgesic Effect through Nav1.8 Channel and MAPKs Pathway

Scorpion species of medical importance in the Brazilian Amazon: a review to identify knowledge gaps

The correlation between interleukin 1β (IL-1β) as an inflammatory marker and Malondialdehyde (MDA) as a lipid peroxidation marker and the development of cardiac and pancreatic complications in humans suspected to scorpion poisoning

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