RESUMO
Oxidative stress and proteases have been implicated in several diseases and extensive evidence indicates that antioxidants and protease inhibitors help prevent organ functional damage. Leiurus quinquestriatus (LQQ) scorpion venom causes cellular injuries that may lead to multiple organ failure. Thus, the capability of the antioxidant "natural standardized extract of Gingko biloba leaves (Gin, EGb 761)" and the non-selective protease inhibitor, aprotinin, in ameliorating venom-induced biochemical alterations indicative of cellular injury and oxidative stress was studied to determine their effectiveness in protecting rats from venom-evoked cellular damages. Thus, in this study, rats were treated with LQQ venom (0.3mg.kg-1, subcutaneously) alone or after Gin (150mg.kg-1, orally, daily for 2 weeks before venom) and/or aprotinin (Apr, 46000 KIU.kg-1, intraperitoneally, 30 min before venom). Control groups were injected with saline or treatment modalities. Lungs and hearts were excised after decapitating rats (n=8/group) 60 min after venom injection and the following activities were measured: reduced glutathione (GSH), malondialdehyde (MDA) - an index of lipid peroxidation, glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), and lactate dehydrogenase (LDH). Our findings demonstrate that LQQ venomsignificantly elevated GSH (p 0.05 vs. control), MDA (p 0.05), G6PD (p 0.05), and LDH activities (p 0.001) in hearts of envenomed rats. The venom also elevated MDA (p 0.05 vs. control) and reduced GSH and GPx (p 0.05) in the lungs of envenomed rats. In general, pretreatment with EGb761 attenuated LQQ venom-evoked increases in GSH (p 0.05 vs. venom), MDA in rat hearts and lungs (p 0.05 vs. venom), plus LDH in the heart (p 0.01). Aprotinin alone significantly reduced the venom-elicited increase in G6PD and LDH activities and the decrease in GPx levels (p 0.05). In general, these protective effects of EGb761 on GSH, MDA (p 0.01 vs. venom) and LDH (p 0.001) in the heart and/or lung were potentiated when combined with aprotinin. We concluded that the effectiveness of EGb761 and Apr in ameliorating venom-evoked biochemical changes indicative of necrosis and free radical generation point out the involvement of oxidative stress and proteases in venom-evoked cellular damages seen in this study in isolated rat hearts and lungs.
RESUMO
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.
