Systemic Responses following Brain Injuries and Inflammatory Process Activation Induced by a Neurotoxin of <b><i>Androctonus</i></b> 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.

Tb II-I, a Fraction Isolated from Tityus bahiensis Scorpion Venom, Alters Cytokines’: Level and Induces Seizures When Intrahippocampally Injected in Rats

“…In addition, when this toxin was subcutaneously injected in rats, it caused an increase in leukocyte rolling and adhesion and high levels of tumoral necrosis factor-α (TNF-α) in the brain [ 14 ]. Moreover, the intracerebroventricular injection of KTX 2 , a toxin isolated from Androctonus australis , caused an inflammatory response in the brain of mice and had consequences on pancreatic and hepatic functions, probably mediated by the release of interleukin-6 (IL-6) and TNF-α [ 15 ].…”

Neuro‐Modulation of Immuno‐Endocrine Response Induced by Kaliotoxin of Androctonus Scorpion Venom

“…The voltage‐gated potassium channels play an important role in diverse physiological processes including the neuronal excitability regulation, neurotransmitter release, and hormone secretion .The potassium channel blockers diversity and their pharmacological specificity enable them to be excellent tools to study some neurological processes. KTX was able to induce severe disturbances in CNS followed by systemic responses . KTX ability to induce thyroid hormones’ synthesis and their release in serum could be attributed to its capacity to stimulate the hypothalamic–pituitary axis since it was able to increase the ROS release leading to an oxidative stress development which could be responsible of the observed tissue damage of hypothalamus and thyroid and the hormone release .…”

“…Recently, previous studies have reported that KTX, injected by i.c.v. route, induced severe alterations on structure and functions of central and peripheral nervous systems associated to an immuno‐inflammatory response . Moreover, these studies showed also that the activation and the release of inflammatory mediators (cytokines, reactive oxygen species, and nitric oxide) may play a crucial role in the pathophysiology of the toxicity and may be responsible of the inflammatory manifestations and organ failure.…”

“…Several studies are reported the direct involvement of the NO in the neurodegenerative diseases processes such as neuronal death, necrosis, and apoptosis and the use of the antioxidant is able to inhibit NO production . Furthermore, considerable lipid peroxidation induced by Aah neurotoxins seems to be the main consequence of free radical generation in brain, pancreas, lungs, and liver tissues of animals . Recently, it has been demonstrated that the obtained antioxidants from natural substances provide a promising strategy against oxidative stress due to their free radical scavenging properties .…”

Partial purification and functional characterization of Ts19 Frag-I, a novel toxin from Tityus serrulatus scorpion venom

“…The α-KTx Ts6 induced NO and IL-6 production and inhibited the release of TNF-α [ 17 ]. Kaliotoxin 2 (KTX 2 ), an α-KTx from Androctonus australis hector scorpion venom, induces severe alterations in hepatic and pancreatic tissues by the activation of the inflammatory response with release of IL-6 and TNF-α [ 32 ]. However, there is no previously published study on the effect of β-KTx on macrophages.…”