Evaluation of lethality and cytotoxic effects induced by Naja ashei (large brown spitting cobra) venom and the envenomation-neutralizing efficacy of selected commercial antivenoms in Kenya

Manson, Ernest Z.; Mutinda, Kyama C.; Gikunju, Joseph Kangangi; Kimani, Josephine; Kimotho, James

doi:10.1016/j.toxcx.2022.100125

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…Previous study of the same specie shows a higher value of 1.4mg/kg for subcutaneous administration (Yahaya et al, 2023). A lower value of 0.324mg/kg for subcutaneous administration and value of 4.6mg/kg for intraperitoneal administration were also reported (Ernest et al, 2022). These differences could be as a result of intra-specie (Jory et al, 2023), regional (Fry et al,2003, age, sex and as a result of different mode of administration (Lidia et al,2022).…”

Section: Discussionmentioning

confidence: 94%

Assessment of Hepatotoxic Effects and Serum Enzyme Changes Induced by Naja melanoleuca Venom in Albino Rats

2023

AJBAR

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Snake envenoming is a crucial problem in west Africa and other parts of the world in which humans and animals are at risk. In this study the intravenous LD 50 of Naja melanoleuca venom was investigated using arithmetic method and the histopathological effect of Naja melonoleuca venom was investigated on the liver of albino mice. The serum enzymes Aspartate Transaminase, Alkaline Transaminase, Alkaline Phosphatase, Albumin and Total Protein levels of mice injected with Naja melanoleuca venom at different doses ((0.1mg/kg,0.2mg/kg,0.4mg/kg,0.8mg/kg and 1.6mg/kg)) were also investigated spectrophotometrically. The intravenous LD 50 assessment of the venom was found to be 0.93mg/kg. The venom induces various cellular changes on the liver tissue, a typical hepatotoxic effect of Naja venom. There was a significant decrease in the AST and ALT level of the serum compared to the control. A significant increase of about 324.00U/L in the ALP level was observed upon injection of 1.6mg/kg of the venom compared to the control. Significant decrease in the ALB level upon injection of the lowest, medium and the highest venom dose was revealed, likewise a significant increase in the TP level upon administration of 1.6mg venom was observed compared to the control group injected with normal saline. Therefore, these findings are essential to elucidate the mechanism underlying the various cellular changes induced by Naja melanoleuca venom and antivenom development.

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Section: Discussionmentioning

confidence: 94%

Assessment of Hepatotoxic Effects and Serum Enzyme Changes Induced by Naja melanoleuca Venom in Albino Rats

2023

AJBAR

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“…Notably, the Inoserp™ antivenom required a slightly higher dose than VINS™ antivenom to achieve the same neutralizing effect. The authors attributed this difference in efficacy to the contrasting protein content of the two antivenom batches: Inoserp™ (28.213 mg/mL) and VINS™ (98.913 mg/mL) [ 51 ]. Resieri and colleagues made observations, highlighting the high efficacy of a monospecific antivenom, which aligned with its previously reported clinical effectiveness.…”

Section: Discussionmentioning

confidence: 99%

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

Khourcha,

Hilal,

Elbejjaj

et al. 2023

TropicalMed

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In Morocco, eight species of venomous snakes belonging to the Viperidae and Elapidae families are responsible for severe envenomation cases. The species from the Elapidae family is only represented by the medically relevant cobra Naja haje, 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 Naja haje 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 Naja haje cobra bites in the Middle East. In this study, we examined the pathophysiological mechanisms responsible for the lethality induced by Naja haje venom, as well as the evaluation of the neutralizing capacity of two antivenoms; the monospecific antivenom made for Naja haje only and the antivenom marketed in the Middle East and North Africa. We first determined the toxicity of Naja haje venom by LD50 test, then compared the neutralizing capacity of the two antivenoms studied by determining the ED50. 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 Naja haje 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 Naja haje antivenom for the effective treatment of cobra envenomation in Morocco.

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“…In this regard, lethality and neurotoxicity among Micrurus species can be ascribed to just a few toxins, mainly PLA 2 and 3FTx families [ 13 , 25 , 39 , 40 ]. This offers the possibility of generating an antivenom comprising a restricted set of anti-PLA 2 and anti-3FTx neutralizing antibodies, like those already developed against certain scorpion and snake venoms [ 48 , 49 , 50 ]. As a proof-of-concept and the first step towards this goal, we have produced and analyzed the immunoreactivity of a set of monoclonal antibodies against the most toxic components of M. altirostris venom.…”

Section: Introductionmentioning

confidence: 99%

Monoclonal-Based Antivenomics Reveals Conserved Neutralizing Epitopes in Type I PLA2 Molecules from Coral Snakes

Corrêa-Netto

Strauch

Monteiro-Machado

et al. 2022

Toxins

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For over a century, polyclonal antibodies have been used to treat snakebite envenoming and are still considered by the WHO as the only scientifically validated treatment for snakebites. Nevertheless, moderate innovations have been introduced to this immunotherapy. New strategies and approaches to understanding how antibodies recognize and neutralize snake toxins represent a challenge for next-generation antivenoms. The neurotoxic activity of Micrurus venom is mainly due to two distinct protein families, three-finger toxins (3FTx) and phospholipases A2 (PLA2). Structural conservation among protein family members may represent an opportunity to generate neutralizing monoclonal antibodies (mAbs) against family-conserved epitopes. In this work, we sought to produce a set of monoclonal antibodies against the most toxic components of M. altirostris venom. To this end, the crude venom was fractionated, and its major toxic proteins were identified and used to generate a panel of five mAbs. The specificity of these mAbs was characterized by ELISA and antivenomics approaches. Two of the generated mAbs recognized PLA2 epitopes. They inhibited PLA2 catalytic activity and showed paraspecific neutralization against the myotoxicity from the lethal effect of Micrurus and Naja venoms’ PLA2s. Epitope conservation among venom PLA2 molecules suggests the possibility of generating pan-PLA2 neutralizing antibodies.

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Evaluation of lethality and cytotoxic effects induced by Naja ashei (large brown spitting cobra) venom and the envenomation-neutralizing efficacy of selected commercial antivenoms in Kenya

Cited by 4 publications

References 32 publications

Assessment of Hepatotoxic Effects and Serum Enzyme Changes Induced by Naja melanoleuca Venom in Albino Rats

Assessment of Hepatotoxic Effects and Serum Enzyme Changes Induced by Naja melanoleuca Venom in Albino Rats

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

Monoclonal-Based Antivenomics Reveals Conserved Neutralizing Epitopes in Type I PLA2 Molecules from Coral Snakes

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