RESUMO
Morocco is one of the richest countries in biodiversity in the Mediterranean region, especially in its ophidian fauna. In total, there are eight species of venomous snakes, with seven belonging to the Viperidae family, responsible for 67.2% of severe envenomation cases in the country. Cerastes cerastes, Daboia mauritanica and Bitis arietans are considered among the most venomous vipers whose bites cause high levels of morbidity, disability or mortality. Despite their wide distribution in the kingdom, the incidence of these snakebites remains poorly understood and largely underestimated. Moreover, intraspecific variations in the venom composition significantly affect the effectiveness of antivenoms. Due to the unavailability of locally produced antivenoms, we evaluated the efficacy of Inoserp-MENA, the only available antivenom in Morocco, against C. cerastes, D. mauritanica and B. arietans. First, we conducted a comprehensive characterization of these venoms, including an LD50 test to examine their toxicity and SDS-PAGE as a technique to analyze the enzymes responsible for biological activities, such as hemorrhagic and edematous activities and myotoxicity, which generate physiopathological effects in the skin, paws and muscles of envenomed mice. Then, we assessed the ability of Inoserp-MENA antivenom to neutralize the toxic activities of Moroccan vipers. Our results indicate that the venom of C. cerastes, D. mauritanica and B. arietans are toxic, causing severe alterations such as edema, myotoxicity, myonecrosis and significant hemorrhages with the formation of hemorrhagic foci. C. cerastes venom is more dangerous in terms of lethality and hemorrhages, while B. arietans venom is more edematous. The effects of C. cerastes venom were effectively neutralized, but Inoserp-MENA antivenom failed to protect mice against the toxic effects induced by B. arietans and D. mauritanica venom. The study reveals alarming shortcomings in the effectiveness of the current commercially available antivenom's dosage and neutralization capabilities, highlighting the urgent need to develop a region-specific viper envenomation therapy.
RESUMO
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.
RESUMO
Morocco is known to harbor two of the world's most dangerous scorpion species: the black Androctonus mauritanicus (Am) and the yellow Buthus occitanus (Bo), responsible for 83% and 14% of severe envenomation cases, respectively. Scorpion venom is a mixture of biological molecules of variable structures and activities, most of which are proteins of low molecular weights referred to as toxins. In addition to toxins, scorpion venoms also contain biogenic amines, polyamines, and enzymes. With the aim of investigating the composition of the Am and Bo venoms, we conducted an analysis of the venoms by mass spectrometry (ESI-MS) after separation by reversed-phase HPLC chromatography. Results from a total of 19 fractions obtained for the Am venom versus 22 fractions for the Bo venom allowed the identification of approximately 410 and 252 molecular masses, respectively. In both venoms, the most abundant toxins were found to range between 2-5 kDa and 6-8 kDa. This proteomic analysis not only allowed the drawing of an extensive mass fingerprint of the Androctonus mauritanicus and Buthus occitanus venoms but also provided a better insight into the nature of their toxins.
