Effect of selected anti-inflammatory drugs on the lethal actions of Leiurus quinquestriatus venom

Abstract

The cumulative actions of scorpion neurotoxins are complex and may be traced to activation of different ion channels with subsequent release of various transmitters and modulators including inflammatory mediators. This could lead to various pathological manifestations such as acute respiratory distress syndrome (ARDS), systemic inflammatory response syndrome (SIRS), and multiple organ failure (MOF). Several approaches have been advocated to treat the multitude of scorpion-venom-elicited pathological changes. However, few have tried to combat the venom-induced effects on the inflammatory process, which manifest as ARDS, SIDS and MOF. Thus, the aim of this study was to determine the capability of inhibitors of different steps of the inflammatory sequence of events in scorpion envenomation to ameliorate the detrimental action of the venom and prolong survival of mice injected with Leiurus quinquestriatus quinquestriatus (LQQ) venom. Animals were divided into groups (n = 10) and given montelukast (10 or 20 mg.kg-1, orally), hydrocortisone (5 or 10 mg.kg-1, intravenously) or indomethacin (10 or 20 mg kg-1, intravenously). Then, all animals were subcutaneously injected with either 0.25 or 0.3 mg.kg-1 LQQ venom. Signs and symptoms of envenomation were recorded and survival percentages after 24 hours as well as survival time were determined in each group. To analyze data, we utilized Covariance Wilcoxon survival statistics and survival distribution curves. In general, when compared to venom alone, administration of montelukast (p<0.001), hydrocortisone (p<0.05) and indomethacin (p<0.05) prolonged survival time and increased the percentage of surviving animals per group, with montelukast exhibiting the greatest protecting power. Thus, anti-inflammatory drugs may play an important role in protection against the lethal effects of scorpion venoms.

Keywords

• Leiurus quinquestriatus quinquestriatus
• scorpion venom
• acute respiratory distress syndrome
• systemic inflammatory response syndrome
• multiple organ failure
• montelukast
• hydrocortisone
• indomethacin