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Age-Related Changes in Inflammatory Response after Experimental Envenomation: Impact on the Susceptibility to
Wassila Haddad-Ishak-Boushaki1, Fatima Laraba-Djebari2
1USTHB, Faculty of Biological Sciences, Laboratory of Cellular and Molecular Biology, BP32, El Alia, Bab Ezzouar, 16111, Algiers, Algeria.
Insights
Young mice are more vulnerable to scorpion stings than adults, showing severe inflammatory responses. This highlights the need for age-specific treatments for scorpion envenomation in children.
Area of Science:
- Toxicology
- Immunology
- Pediatrics
Background:
- Children are primary victims of scorpion envenomation, experiencing more severe symptoms and higher mortality.
- The exact mechanisms behind children's increased susceptibility to scorpion stings are not well understood.
- Inflammatory responses are central to envenomation pathophysiology, but age-related differences are understudied.
Purpose of the Study:
- To compare systemic and central inflammatory responses to Androctonus australis hector (Aah) venom in immature (7 and 21 postnatal days) and adult mice.
- To investigate age-dependent differences in immune cell activation, oxidative stress markers, and tissue damage following scorpion envenomation.
Main Methods:
- Subcutaneous injection of Aah venom into mice at different postnatal ages (7, 21 days) and adulthood.
- Assessment of systemic (blood, lung) and central (brain) inflammatory markers, including immune cell counts, nitric oxide (NO) levels, lipid peroxidation, and antioxidant status (GSH, catalase).
- Histopathological evaluation of lung and brain tissues for alterations and edema.
Main Results:
- Immature mice (7 and 21 pnd) exhibited greater sensitivity to Aah venom compared to adults.
- Younger mice showed heightened systemic and central inflammatory responses, characterized by increased immune cell activation, NO liberation, and lipid peroxidation.
- Reduced levels of antioxidants (GSH, catalase) in immature mice correlated with more severe tissue damage and edema in the lungs and brain.
- Neutrophil levels were higher, and lymphocyte levels lower in immature mice compared to adults.
Conclusions:
- Age is a critical factor influencing the severity of pathophysiological effects from Aah venom.
- The heightened vulnerability of immature animals to scorpion venom may stem from dysregulated inflammatory responses and central nervous system disturbances.
- Findings underscore the necessity for developing age-tailored therapeutic strategies for scorpion envenomation, particularly for pediatric populations.
Abstract:
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.