ABSTRACT
Aims: South Brazilian Hypericum species are a source of dimeric structures, constituted of filicinic acid and phloroglucinol moieties, which present antidepressant-like effects mediated by monoaminergic neurotransmission in rodents. Here, we show that hyperbrasilol B, a phloroglucinol derivative from Hypericum caprifoliatum, presents antidepressant-like activity in mice forced swimming test (FST). The aim of this study was to determinate if Na+ channels are important to the antidepressant-like effect of hyperbrasilol B and also verify the effect of this compound on Na+, K+ ATPase activity in the cerebral cortex and hippocampus of mice. Methodology: We assessed the effects of veratrine, a Na+ channel opener on antidepressant-like effect of hyperbrasilol B by using mice FST. Veratrine (0.06 mg/kg) and hyperbrasilol B (10 mg/kg) were given i.p. 60 and p.o. 30 min, respectively, before the test. In another batch of experiments different groups of mice were treated with hyperbrasilol B 10 mg/kg, p.o. (Single administration or once a day during 3 days). Two hours after the acute or after the last of the three treatments, the brain structures were removed for measuring Na+, K+ ATPase activity. Results: Veratrine was able to prevent the anti-immobility effect of hyperbrasilol B on the FST, suggesting that its antidepressant-like effect might be due to Na+ influx modifying properties. Animals treated for 3 consecutive days with hyperbrasilol B presented a significant increase in the hippocampus Na+, K+ ATPase activity. The acute treatment was ineffective. Conclusion: Alterations in the Na+ gradient may be implicated in the antidepressant-like effect of hyperbrasilol B.
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.(AU)