ABSTRACT
Kaliotoxin (KTX), a specific blocker of potassium channels, exerts various toxic effects due to its action on the central nervous system. Its use in experimental model could help the understanding of the cellular and molecular mechanisms involved in the neuropathological processes related to potassium channel dysfunctions. In this study, the ability of KTX to stimulate neuro-immuno-endocrine axis was investigated. As results, the intracerebroventricular injection of KTX leads to severe structural-functional alterations of both hypothalamus and thyroid. These alterations were characterized by a massive release of hormones' markers of thyroid function associated with damaged tissue which was infiltrated by inflammatory cell and an imbalanced redox status. Taken together, these data highlight that KTX is able to modulate the neuro-endocrine response after binding to its targets leading to the hypothalamus and the thyroid stimulation, probably by inflammatory response activation and the installation of oxidative stress in these organs.
Subject(s)
Eosinophils/drug effects , Hypothalamus/drug effects , Neutrophils/drug effects , Scorpion Venoms/toxicity , Scorpions/chemistry , Thyroid Gland/drug effects , Animals , Calcitonin/biosynthesis , Calcitonin/metabolism , Catalase/metabolism , Eosinophils/immunology , Glutathione/metabolism , Hypothalamus/immunology , Hypothalamus/metabolism , Injections, Intraventricular , Malondialdehyde/metabolism , Mice , Neutrophil Infiltration/drug effects , Neutrophils/immunology , Nitriles/metabolism , Oxidation-Reduction , Oxidative Stress , Scorpion Venoms/isolation & purification , Scorpions/physiology , Thyroid Gland/immunology , Thyroid Gland/metabolism , Thyrotropin/biosynthesis , Thyrotropin/metabolism , Thyroxine/biosynthesis , Thyroxine/metabolism , Triiodothyronine/biosynthesis , Triiodothyronine/metabolismABSTRACT
OBJECTIVE: Kaliotoxin (KTX) is a neurotoxin purified from Androctonus scorpion venom. Purification and pharmacological and immunological characterization of this neurotoxin has been extensively studied, but its biological effects have not. The ability of KTX to induce neuropathophysiological and immuno-inflammatory effects was investigated. METHODS: NMRI mice were injected with a sublethal dose of KTX (20 ng/20 g of body weight) or saline solution via the intra-cerebro-ventricular route. Tissue damage and immunological biomarkers such as eosinophil peroxidase (EPO), myeloperoxidase (MPO), and nitric oxide (NO) were analyzed in serum, brain, lung, and heart tissue. Protein levels, LDH, and CPK activities were also determined in serum 24 h after injection. RESULTS: In this study, KTX injection induced severe alterations in the cerebral cortex, myocardium, and pulmonary parenchyma. Tissue damage was correlated with seric increase in creatine kinase and lactate dehydrogenase activities. KTX also induced an immuno-inflammatory response distinguished by cell infiltration characterized by a significant increase in EPO and MPO activities in the brain, heart, and lungs. This infiltration was also associated with an increase in albumin, α-, ß-, and γ-globulin fractions, and NO release. CONCLUSION: KTX binding to its targets in CNS (Kv1.1 and Kv1.3 channels) may induce severe modifications in the structure and function of various organs associated with the activation of immuno-inflammatory reactions.
