The effects of a sodium and a calcium channel blocker on lethality of mice injected with the yellow scorpion (Leiurus quinquestriatus) venom

Abstract

Scorpion venom toxins generally produce similar effects by mainly acting on sodium channels, and to a lesser extent, on potassium, calcium, and chloride channels. This leads to increased release of neurotransmitters and mediators, resulting in a cascade of pathological events, involving the central nervous system, the autonomic nervous system, the cardiovascular and the respiratory system, eventually leading to death. The objective of this paper was to discover whether a sodium channel blocker, lidocaine, or a calcium channel blocker, verapamil, would prolong the survival of mice injected with the venom from the common yellow scorpion Leiurus quinquestriatus quinquestriatus (LQQ). For this purpose, mice were divided into 2 groups, each injected with a different venom dose (250 or 300 µg.kg-1, s.c.). Subgroups (n=10) from each group were given venom alone; different doses of lidocaine (4, 10, 15, or 20 mg.kg-1); or several doses of verapamil (0.01, 0.03, 0.1, 0.3, or 1 mg.kg-1). All doses of lidocaine and verapamil were intravenously administered 3 minutes before, 1, 5, and 15 minutes after venom injection. Percent surviving after 24 hours was recorded in addition to the time of death. In general, lidocaine significantly prolonged survival at the dose of 10 mg.kg-1 (P<0.05 and P<0.01, versus low and high dose of venom, respectively) or 15 mg.kg-1 (P<0.01 and P<0.001, versus low and high dose of venom, respectively; Covariance Wilcoxon survival statistics), especially when injected before the venom or in the early stages of envenomation. On the other hand, in all doses administered, verapamil was either toxic or showed non-significant results. Lidocaine, the sodium channel blocker, appears to play an important role in the protection from lethality of mice injected with LQQ venom, and significantly prolonged the survival time of mice whether injected before or in the early stages of envenomation

Cardiac disorders and mode of action of the Egyptian scorpion venom Androctonus bicolor on isolated toad’s heart

“…4C and D), it can be proposed that L-type calcium channels are not engaged in the stimulatory effect of A. bicolor. The same finding was obtained in vivo by Al-Shanawani et al, 2005 who found that verapamil could not protect the mice injected with the venom of L. quinquestriatus.…”

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

“…It is clear that venom-evoked Na + channel activation is the first step in the cascade of events that take place after scorpion envenomation and several studies have demonstrated its efficacy in protecting animals from peripherally injected scorpion venom (Fatani et al, 2000(Fatani et al, , 2010Vital et al, 2002;Al-Shanawani et al, 2005). Moreover, several investigators have shown that several a neurotoxins, including those present in LQQ venom, have higher affinity for peripheral sodium channels than for those of the central nervous system (Hamon et al, 2002;Kopeyan et al, 2006).…”

“…Toxic manifestations of scorpion venom toxins are due to their ability to act mainly on Na + and to a lesser degree K + and Ca 2+ channels, prolonging depolarization, causing massive release of neurotransmitters and modulators and thus affecting different systems. Treatment with channel blockers have been shown to protect animals from systemic pathological manifestations and lethality of animals injected peripherally with LQQ scorpion venom (Fatani et al, 2000(Fatani et al, , 2010Vital et al, 2002;Al-Shanawani et al, 2005).…”

“…The relationship between venom-elicited effects following either central or peripheral injection of scorpion venoms requires further investigation, especially with venom from Old World Scorpions common in the Middle East, where few studies have been performed. Moreover, it needs to be assessed whether the Na + channel blocker, lidocaine, is as effective against centrally-injected venom as it is against venom inoculated peripherally (Fatani et al, 2000(Fatani et al, , 2010Al-Shanawani et al, 2005).…”

Dose-dependent effect of carbamazepine on weanling rats submitted to subcutaneous injection of tityustoxin

“…These results are consistent with other toxicological reports, which used neurotropic agents that targeted voltagegated sodium channels (VGSCs). Al-Shanawani et al showed that mice pre-treated with lignocaine survived longer after the inoculation of the Leiurus quinquestriatus venom than animals that received only vehicle [1]. The best results were obtained when the mice were treated minutes before the venom inoculation.…”