Age-Related Changes in Inflammatory Response after Experimental Envenomation: Impact on the Susceptibility to Androctonu
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ORIGINAL ARTICLE
Age-Related Changes in Inflammatory Response after Experimental Envenomation: Impact on the Susceptibility to Androctonus australis hector Venom Wassila Haddad-Ishak-boushaki1 and Fatima Laraba-Djebari1,2
In regions at risk of scorpion envenomation, children remain the principal victims; they exhibit severe symptoms and represent a higher mortality rate compared to adults. The pathophysiology of envenomation is related to an excessive inflammatory response; however, no studies have identified the differences in immune responses to scorpion stings and mainly the mechanisms of inflammation between children and adults, which may be a determinant key of the susceptibility of children to scorpion envenomation. In this study, we compared the systemic (blood and lung) and the central (brain) inflammatory responses after injection of Androctonus australis hector (Aah) venom to 7 and 21 postnatal days (pnds) and adult mice by subcutaneous route. Results revealed that 7 and 21 pnd mice were more sensitive to Aah venom than adults and presented also severe systemic and central inflammatory responses characterized by a high activation of immune cells, NO liberation, and lipid peroxidation. Lymphocyte levels were much lower in young animals than in adults; however, neutrophil levels seemed to be higher in immature mice. The antioxidant GSH and catalase levels were more reduced in 7 and 21 pnd mice compared to adults leading to more pronounced tissular alterations and edema formation in lung and brain. These findings show a relationship between the severity of the pathophysiological effects of Aah venom and the age. The vulnerability of immature animals to Aah venom might result from uncontrolled inflammatory response and central nervous system alterations. Data from the present study emphasize the need for the development of age-specific therapeutic modalities. Abstract—
KEY WORDS: scorpion venom; Androctonus australis hector; inflamatory response; age; immune system maturation.
INTRODUCTION Scorpion stings are responsible for hundreds of thousands of cases of envenomation. Children constitute the major population at risk presenting severe symptoms and 1
USTHB, Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, BP32, El Alia, Bab Ezzouar, 16111 Algiers, Algeria 2 To whom correspondence should be addressed at USTHB, Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, BP32, El Alia, Bab Ezzouar, 16111 Algiers, Algeria. E-mail: [email protected]
higher mortality rate compared to adults [7, 13, 17, 21]. The mechanism of action of scorpion venom is related to the binding of its neurotoxins on voltage-gated sodium channels of neuronal terminals, leading to a release of neuromediators. These neuromediators induce a variety of clinical effects such as cardiac failure, pulmonary edema, convulsions, and death of the victim [1, 42]. Several studies associate the neurotoxic action to the peripheral nervous system [19]. However, central nervous system (CNS) manife
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