Divergent clinical, inflammatory, and histopathological responses induced by Amazonian Tityus venoms: insights and limitations of current antivenom therapy.

Scorpion stings are considered a neglected condition and represent a serious health problem in many tropical countries, especially for children and the elderly. In Brazil, the yellow scorpion (Tityus serrulatus) is widely found and responsible for the majority of severe envenoming cases; however, other medically relevant species endemic to the Brazilian Amazon region, such as Tityus silvestris, Tityus metuendus and Tityus obscurus, remain underexplored. In the present study, we characterized the clinical, inflammatory and histopathological responses induced by venoms from these Amazonian species in a murine model (Balb/c mice), using T. serrulatus as a reference. Envenomation with T. silvestris resulted in pronounced systemic manifestations, including elevated clinical scores, hyperglycemia, leukocytosis, cytokine release (IL-6, IL-1β, IL-10), and tissue injury in the lungs and kidneys, comparable to the pathophysiological manifestations from T. serrulatus venom. In contrast, T. metuendus and T. obscurus induced milder inflammatory profiles. It is noteworthy that cross-reactivity assays revealed limited immunoreactivity and reduced in vivo neutralization of T. metuendus and T. obscurus venoms by the commercially available T. serrulatus-based antivenom. These findings reveal critical limitations in relying on a single-species antivenom for treating scorpion envenomation across diverse regions and underscore the need for region-specific therapeutic strategies tailored to the distinct venom profiles and pathogenicity of Amazonian Tityus species.