title: Comparative study between peripherally and centrally acting sublethal and lethal doses of Leiurus quinquestriatus scorpion venom in rabbits: The usefulness of the sodium channel blocker lidocaine.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacology, College of Pharmacy, King Saud University, Saudi Arabia.
authors: Amal J
authors: AJ
authors: Fatani
keywords: Blood pressure; Cardiac output; Estimated hepatic blood flow; Histopathological manifestations; Leiurus quinquestriatus; Lidocaine; Pulmonary index; Scorpion venom
references: Life Sci. 2000;66(3):185-92
references: 10665992
references: Toxicon. 2001 Jun;39(6):781-5
references: 11137536
references: Toxicol Appl Pharmacol. 2007 May 1;220(3):235-42
references: 17320922
references: Toxicon. 2007 Dec 1;50(7):984-92
references: 17854855
references: Med Sci Monit. 2005 Apr;11(4):CR196-202
references: 15795701
references: Acta Neurochir (Wien). 1988;93(1-2):37-44
references: 3414415
references: Toxicon. 2000 Dec;38(12):1787-801
references: 10858517
references: Life Sci. 2003 Jun 6;73(3):319-25
references: 12757839
references: Toxicon. 2010 Apr 1;55(4):773-86
references: 19931297
references: Toxicol Appl Pharmacol. 2003 Feb 15;187(1):58-66
references: 12628585
references: Neurotoxicology. 2009 Jan;30(1):90-6
references: 18996147
references: Toxicon. 2003 Jun;41(8):971-7
references: 12875871
references: Toxicon. 1996 Oct;34(10):1119-25
references: 8931252
references: Toxicon. 1997 Jan;35(1):13-4
references: 9028004
references: Curr Opin Crit Care. 2007 Apr;13(2):207-14
references: 17327744
references: Anal Chem. 1991 Nov 15;63(22):2603-7
references: 1776699
references: J Nat Toxins. 2002 Feb;11(1):1-13
references: 11829056
references: N Engl J Med. 2009 May 14;360(20):2090-8
references: 19439743
references: Eur J Biochem. 2002 Aug;269(16):3920-33
references: 12180969
references: Toxicon. 1992 Oct;30(10):1257-79
references: 1279839
references: J Assoc Physicians India. 2009 Apr;57:301-4
references: 19702035
references: Nat Toxins. 1993;1(5):308-12
references: 8167952
references: Toxicon. 1995 Jul;33(7):825-58
references: 8588209
references: Toxicon. 2009 Sep 15;54(4):471-80
references: 19467253
references: Toxicon. 1994 Dec;32(12):1641-7
references: 7725331
references: Toxicon. 2005 Feb;45(2):187-98
references: 15626368
references: Toxicon. 1977;15(3):225-34
references: 867438
references: J Med. 1993;24(1):10-27
references: 8501401
references: Toxicon. 2003 Jan;41(1):49-55
references: 12467661
references: Pharmacol Biochem Behav. 1998 May;60(1):7-14
references: 9610917
references: Hum Exp Toxicol. 2009 Nov;28(11):721-8
references: 19812121
references: Toxicon. 1998 Mar;36(3):523-36
references: 9637372
references: Neurosci Lett. 2009 Oct 9;463(3):234-8
references: 19664683
references: Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1995 Jun;111(2):183-90
references: 8521241
references: Toxicon. 1993 Feb;31(2):205-12
references: 8456448
references: Toxicon. 1999 May;37(5):771-82
references: 10219988