Department of Pharmacology, College of Pharmacy, King Saud University, Saudi Arabia.
Saudi Pharm J. 2010 Jul;18(3):137-51. doi: 10.1016/j.jsps.2010.05.007. Epub 2010 May 31.
Scorpion envenomation is common among desert dwellers, affecting several systems and resulting in multiple organ dysfunction (MOD) or failure (MOF), mainly due to their action on Na(+) channels. Although scorpion venoms toxins do not pass the blood brain barrier, their CNS effects are prominent, occurring in conjunction with, or as an aftermath of peripheral actions of the venom.
To determine the ability of venom of the common scorpion Leiurus quinquestriatus (LQQ) to induce MOD or MOF when injected into rabbits in micro quantities centrally (intracerebroventricularly, i.c.v.) or macro amounts peripherally (s.c. or i.v.). Also, to assess if the Na(+) channel blocker lidocaine can protect rabbits from the resultant manifestations.
Rabbits were injected with LQQ venom centrally or peripherally, in either sublethal or lethal doses, and MOD or MOF determined by assessing: cardiac output (CO), estimated hepatic blood flow (EHBF), biochemical parameters indicative of cardiac/hepatic/renal and pancreatic functions, blood pressure (BP), survival, lung/body index (LBI, indicative of pulmonary edema), and/or histological changes in hearts, lungs, livers plus kidneys. In pre-treatment experiments, lidocaine was injected 40 min before venom and protective ability examined.
LQQ venom in sublethal doses caused comparable significant reductions (vs control) in CO and EHBF when injected i.c.v. (2 μg kg(-1)) or s.c. (0.2 mg kg(-1)). Both routes caused gradual dose-related enhanced levels of creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatinine, glucose and amylase, indicating MOD. Also, characteristic venom-induced changes in BP were evident after lethal doses of venom i.v. (0.5 mg kg(-1)) or i.c.v. (3 μg kg(-1)). Histological changes in the organs plus LBI were comparable after i.c.v. and i.v. venom injection, with animals ultimately exhibiting MOF. Lidocaine (1 mg kg(-1) i.v., then infusion 50 μg kg(-1) min(-1), 30 min before venom), protected the animals from MOF evoked by lethal doses of the venom (whether injected centrally or peripherally), as evidenced by the amelioration of the venom's effects on blood pressure, LBI, survival and multiple organ histopathological manifestations.
LQQ venom, whether injected centrally or peripherally caused comparable systemic dose-dependent MOD or MOF, with the latter attenuated by the Na(+) channel blocker lidocaine, indicating a role for Na(+) channels.
蝎子蛰伤在沙漠居民中很常见，会影响多个系统，导致多器官功能障碍（MOD）或衰竭（MOF），主要是由于它们对钠离子通道的作用。尽管蝎子毒液毒素不能穿透血脑屏障，但它们对中枢神经系统的影响很明显，与毒液的外周作用同时发生，或作为其后果。
确定微量（脑室内，i.c.v.）或大量（皮下或静脉内，s.c.或 i.v.）注射常见蝎子 Leiurus quinquestriatus（LQQ）毒液时，毒液是否能够诱导兔子发生 MOD 或 MOF。还评估钠离子通道阻滞剂利多卡因是否能保护兔子免受由此产生的影响。
兔子接受 LQQ 毒液脑室内或外周注射，剂量为亚致死或致死剂量，并通过评估以下参数确定 MOD 或 MOF：心输出量（CO）、估计肝血流量（EHBF）、心脏/肝脏/肾脏和胰腺功能的生化参数、血压（BP）、存活、肺/体指数（LBI，提示肺水肿）和/或心脏、肺、肝加肾的组织学变化。在预处理实验中，在毒液注射前 40 分钟注射利多卡因，并检查其保护能力。
LQQ 毒液在亚致死剂量时，无论是脑室内（2μg/kg）还是皮下（0.2mg/kg）注射，都会导致 CO 和 EHBF 显著降低（与对照组相比）。两种途径都会导致逐渐的剂量相关的肌酸激酶、乳酸脱氢酶、天门冬氨酸氨基转移酶、丙氨酸氨基转移酶、肌酐、葡萄糖和淀粉酶水平升高，表明发生了 MOD。此外，在静脉注射（0.5mg/kg）或脑室内注射（3μg/kg）致死剂量的毒液后，可见到特征性的毒液诱导的血压变化。脑室内和静脉内注射毒液后，器官的组织学变化和 LBI 相似，最终导致 MOF。利多卡因（静脉内 1mg/kg，然后在毒液前 30 分钟内以 50μg/kg/min 的速度输注）可保护动物免受致死剂量毒液引起的 MOF，这从毒液对血压、LBI、存活率和多个器官组织病理学表现的影响的改善中得到证实。
LQQ 毒液无论是脑室内还是外周注射，都会导致类似的、系统的、剂量依赖性的 MOD 或 MOF，钠离子通道阻滞剂利多卡因可减轻后者，表明钠离子通道的作用。
