Taibi-Djennah Zahida, Matin-Eauclaire Marie-France, Laraba-Djebari Fatima
Laboratory of Cellular and Molecular Biology, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumdiene, Algiers, Algeria.
Neuroimmunomodulation. 2015;22(6):347-57. doi: 10.1159/000371493. Epub 2015 Feb 28.
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.
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.
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.
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.
卡利毒素2（KTX2）是一种从澳链尾蝎毒液中分离出的神经毒素，对电压门控钾通道具有高亲和力。KTX2在大脑中的靶点及其对大脑皮层的毒性作用已得到广泛研究；然而，其对其他器官系统的有害全身影响尚未得到研究。KTX2诱导的炎症反应由细胞因子释放介导，这可能引发哺乳动物的多器官功能障碍和多种生物学紊乱。研究了KTX2诱导的炎症反应和脑损伤是否可能导致功能障碍，例如在胰腺和肝脏中。还测试了白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）对KTX2诱导的病理生理效应调节的作用。
通过脑室内注射途径给NMRI小鼠注射亚致死剂量的KTX2或盐溶液。评估血清和组织匀浆中的炎症反应和氧化应激。还分析了胰腺和肝功能的生物标志物以及与脑、肝和胰腺组织损伤的相关性。
所得结果表明，注射KTX2会诱导炎症过程激活和氧化还原状态失衡。它还会导致大脑皮层、肝脏和胰腺组织发生严重改变，同时胰腺和肝脏病理生物标志物显著增加。在注射KTX2前30分钟注射细胞因子拮抗剂可显著减轻KTX2诱导的所有紊乱。
除了对中枢神经系统有显著毒性外，KTX2还可能通过涉及IL-6和TNF-α释放激活炎症反应的间接机制影响胰腺和肝功能。
