Assessing the Efficacy of Monovalent and Commercialized Antivenoms for Neutralizing Moroccan Cobra <i>Naja haje</i> Venom: A Comparative Study

In Morocco, eight species of venomous snakes belonging to the <i>Viperidae</i> and <i>Elapidae</i> families are responsible for severe envenomation cases. The species from the <i>Elapidae</i> family is only represented by the medically relevant cobra <i>Naja...

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Main Authors: Soukaina Khourcha, Ines Hilal, Iatimad Elbejjaj, Mehdi Karkouri, Amal Safi, Abdelaziz Hmyene, Naoual Oukkache
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Tropical Medicine and Infectious Disease
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Online Access:https://www.mdpi.com/2414-6366/8/6/304
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author Soukaina Khourcha
Ines Hilal
Iatimad Elbejjaj
Mehdi Karkouri
Amal Safi
Abdelaziz Hmyene
Naoual Oukkache
author_facet Soukaina Khourcha
Ines Hilal
Iatimad Elbejjaj
Mehdi Karkouri
Amal Safi
Abdelaziz Hmyene
Naoual Oukkache
author_sort Soukaina Khourcha
collection DOAJ
description In Morocco, eight species of venomous snakes belonging to the <i>Viperidae</i> and <i>Elapidae</i> families are responsible for severe envenomation cases. The species from the <i>Elapidae</i> family is only represented by the medically relevant cobra <i>Naja haje</i>, which is widely distributed in North Africa. However, there is little information on the systemic effects of Moroccan cobra venom on vital organs due to regional variations. It has been demonstrated that the venom of <i>Naja haje</i> from Egypt causes hemorrhage, while the venom of the Moroccan cobra is neurotoxic and devoid of systemic bleeding. This variability is known to significantly influence treatment efficacy against <i>Naja haje</i> cobra bites in the Middle East. In this study, we examined the pathophysiological mechanisms responsible for the lethality induced by <i>Naja haje</i> venom, as well as the evaluation of the neutralizing capacity of two antivenoms; the monospecific antivenom made for <i>Naja haje</i> only and the antivenom marketed in the Middle East and North Africa. We first determined the toxicity of <i>Naja haje</i> venom by LD<sub>50</sub> test, then compared the neutralizing capacity of the two antivenoms studied by determining the ED<sub>50</sub>. We also performed histological analysis on Swiss mice envenomed and treated with these antivenoms to observe signs of cobra venom envenomation and the degree of reduction of induced systemic alterations. The results showed significant differences between both antivenoms in terms of neutralization. The monospecific antivenom was four times more effective than the marketed antivenom. These results were confirmed by a histological study, which showed that monospecific antivenoms neutralized severe signs of mortality, such as congestion of blood vessels in the heart and kidneys, pulmonary and renal edema, cytoplasmic vacuolization of hepatocytes in the liver, and infiltration of inflammatory cells in the brain and spleen. However, the polyvalent antivenom failed to protect all severe lesions induced by <i>Naja haje</i> venom in mice. These findings highlight the negative impact of geographic variation on the effectiveness of conventional antivenom therapy and confirm the need for a specific <i>Naja haje</i> antivenom for the effective treatment of cobra envenomation in Morocco.
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spelling doaj.art-1f53b879c7ce4286b063ae0349c382642023-11-18T12:56:18ZengMDPI AGTropical Medicine and Infectious Disease2414-63662023-06-018630410.3390/tropicalmed8060304Assessing the Efficacy of Monovalent and Commercialized Antivenoms for Neutralizing Moroccan Cobra <i>Naja haje</i> Venom: A Comparative StudySoukaina Khourcha0Ines Hilal1Iatimad Elbejjaj2Mehdi Karkouri3Amal Safi4Abdelaziz Hmyene5Naoual Oukkache6Laboratory of Venoms and Toxins, Pasteur Institute of Morocco, Casablanca 20360, MoroccoLaboratory of Venoms and Toxins, Pasteur Institute of Morocco, Casablanca 20360, MoroccoLaboratory of Pathological Anatomy, University Hospital Center Ibn Rochd, Casablanca 20250, MoroccoLaboratory of Pathological Anatomy, University Hospital Center Ibn Rochd, Casablanca 20250, MoroccoLaboratory of Biochemistry, Environment and Food Technology, Faculty of Sciences and Technologies of Mohammedia, Hassan II University, Mohammedia 20650, MoroccoLaboratory of Biochemistry, Environment and Food Technology, Faculty of Sciences and Technologies of Mohammedia, Hassan II University, Mohammedia 20650, MoroccoLaboratory of Venoms and Toxins, Pasteur Institute of Morocco, Casablanca 20360, MoroccoIn Morocco, eight species of venomous snakes belonging to the <i>Viperidae</i> and <i>Elapidae</i> families are responsible for severe envenomation cases. The species from the <i>Elapidae</i> family is only represented by the medically relevant cobra <i>Naja haje</i>, which is widely distributed in North Africa. However, there is little information on the systemic effects of Moroccan cobra venom on vital organs due to regional variations. It has been demonstrated that the venom of <i>Naja haje</i> from Egypt causes hemorrhage, while the venom of the Moroccan cobra is neurotoxic and devoid of systemic bleeding. This variability is known to significantly influence treatment efficacy against <i>Naja haje</i> cobra bites in the Middle East. In this study, we examined the pathophysiological mechanisms responsible for the lethality induced by <i>Naja haje</i> venom, as well as the evaluation of the neutralizing capacity of two antivenoms; the monospecific antivenom made for <i>Naja haje</i> only and the antivenom marketed in the Middle East and North Africa. We first determined the toxicity of <i>Naja haje</i> venom by LD<sub>50</sub> test, then compared the neutralizing capacity of the two antivenoms studied by determining the ED<sub>50</sub>. We also performed histological analysis on Swiss mice envenomed and treated with these antivenoms to observe signs of cobra venom envenomation and the degree of reduction of induced systemic alterations. The results showed significant differences between both antivenoms in terms of neutralization. The monospecific antivenom was four times more effective than the marketed antivenom. These results were confirmed by a histological study, which showed that monospecific antivenoms neutralized severe signs of mortality, such as congestion of blood vessels in the heart and kidneys, pulmonary and renal edema, cytoplasmic vacuolization of hepatocytes in the liver, and infiltration of inflammatory cells in the brain and spleen. However, the polyvalent antivenom failed to protect all severe lesions induced by <i>Naja haje</i> venom in mice. These findings highlight the negative impact of geographic variation on the effectiveness of conventional antivenom therapy and confirm the need for a specific <i>Naja haje</i> antivenom for the effective treatment of cobra envenomation in Morocco.https://www.mdpi.com/2414-6366/8/6/304<i>Naja haje</i>cobra venomtoxicityphysiopathologyhistologyantivenom neutralization
spellingShingle Soukaina Khourcha
Ines Hilal
Iatimad Elbejjaj
Mehdi Karkouri
Amal Safi
Abdelaziz Hmyene
Naoual Oukkache
Assessing the Efficacy of Monovalent and Commercialized Antivenoms for Neutralizing Moroccan Cobra <i>Naja haje</i> Venom: A Comparative Study
Tropical Medicine and Infectious Disease
<i>Naja haje</i>
cobra venom
toxicity
physiopathology
histology
antivenom neutralization
title Assessing the Efficacy of Monovalent and Commercialized Antivenoms for Neutralizing Moroccan Cobra <i>Naja haje</i> Venom: A Comparative Study
title_full Assessing the Efficacy of Monovalent and Commercialized Antivenoms for Neutralizing Moroccan Cobra <i>Naja haje</i> Venom: A Comparative Study
title_fullStr Assessing the Efficacy of Monovalent and Commercialized Antivenoms for Neutralizing Moroccan Cobra <i>Naja haje</i> Venom: A Comparative Study
title_full_unstemmed Assessing the Efficacy of Monovalent and Commercialized Antivenoms for Neutralizing Moroccan Cobra <i>Naja haje</i> Venom: A Comparative Study
title_short Assessing the Efficacy of Monovalent and Commercialized Antivenoms for Neutralizing Moroccan Cobra <i>Naja haje</i> Venom: A Comparative Study
title_sort assessing the efficacy of monovalent and commercialized antivenoms for neutralizing moroccan cobra i naja haje i venom a comparative study
topic <i>Naja haje</i>
cobra venom
toxicity
physiopathology
histology
antivenom neutralization
url https://www.mdpi.com/2414-6366/8/6/304
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