Systemic Responses following Brain Injuries and Inflammatory Process Activation Induced by a Neurotoxin of Androctonus Scorpion Venom

Abstract

Objective: Kaliotoxin 2 (KTX₂), a neurotoxin isolated from Androctonus australis hector scorpion venom, presents a high affinity with the voltage-gated potassium channels. The targets of KTX₂ in the brain and its toxic effects on the cerebral cortex have been extensively studied; however, its deleterious systemic effects on other organ systems have not yet been investigated. Inflammatory response induced by KTX₂ is supported by cytokine release which could provoke multiple organ dysfunction and diverse biological disorders in mammals. The possibility that inflammatory response and brain injuries induced by KTX₂ may lead to functional disturbances, e.g. in the pancreas and the liver, were investigated. The contribution of IL-6 and TNF-α to the modulation of pathophysiological effects induced by KTX₂ was also tested. Methods: NMRI mice were injected by the intracerebroventricular route with a sublethal dose of KTX₂ or saline solution. Inflammatory response and oxidative stress were assessed in sera and tissue homogenates. Biomarkers of pancreatic and hepatic functions and the correlation with tissue damage in the brain, liver and pancreas were also analyzed. Results: The obtained results revealed that KTX₂ injection induced an inflammatory process activation and imbalanced redox status. It also induced severe alterations in cerebral cortex, hepatic and pancreatic tissues associated with a significant increase in pancreatic and hepatic pathological biomarkers. Cytokine antagonists injected 30 min prior to KTX₂ led to a significant reduction of all disturbances induced by KTX₂. Conclusion: In addition to its significant toxicity on the central nervous system, KTX₂ can also affect pancreatic and hepatic functions, probably by an indirect mechanism involving activation of the inflammatory response with release of IL-6 and TNF-α.