Quercitrin attenuates the neurotoxic effect caused by in vivo exposure to MeHg.

Introduction: Exposure to methymercury (MeHg) can cause irreversible neurobehavioral and neuropsychological disorders in humans and animals. The major mechanisms of MeHg-induced neurotoxicity currently being explored are the disruption of intracellular calcium homeostasis, induction of oxidative stress, depletion of endogenous thiols pool, inhibition of neuronal Na+/K+ -ATPase and negative modulation of antioxidant enzymes. Flavonoids can counteract the in vitro lipid peroxidation and ROS production induced by MeHg. Recently, it was demonstrated that quercitrin caused an exacerbation of MeHg neurotoxicity.Methods: In view of the apparent discrepancy between in vitro and in vivo data, here we evaluated the potential neuroprotective effect of quercitrin (10mg/kg) against MeHg. Mice were treated during 30 days with MeHg (5mg/kg, p.o.) and co-treated with quercitrin (10mg/kg, i.p.). Along the treatment animals were subjected to behavioral/ functional tests for evaluating locomotor activity (open field), coordination (rota road) and spatial memory (plus maze tasks). After treatment, animals were killed by decapitation and cerebellum, brain and kidney were removed and homogenized in tris – HCl 10mM, pH 7.4.Results: MeHg reduced body weight gain, increased micronucleos frequencies, caused nefrotoxicity, impaired motor performance (locomotor activity and motor coordination), disrupt spatial memory deficiency and altered biochemical endpoints of toxicity (i.e., it caused a decrease in glutathione peroxidase and Na+/K+ ATPase activity and an increase in lipid peroxidation). The co-treatment with quercitrin mitigated some of the toxic consequences of MeHg exposure. Discussion: In this study, MeHg caused marked decrease in cerebellar GPx activity, suggesting a possible involment of cerebellar injury in motor alteration caused by MeHg. quercitrin failed to protect against MeHg, suggesting that the absence of neurobehavioral protection by quercitrin unprotection is related with inability of quercitrin in maintained the cerebellar GPx levels. The with MeHg treatment caused an inhibition in brain Na+/K+ATPase, which can be associated with locomotor impairments and spatial memory deficits caused by MeHg treatment. Additionally, quercitrin co-treatment protected Na+/K+ ATPase against MeHg inhibition, suggesting a mechanism via which quercitrin could afford behavioral protection against MeHg neurotoxicity. In adittion the protective effect exerted by quercitrin against brain LPO can be one mechanism via which quercitrin promotes neuroprotection against pro-oxidant neurotoxicants.Conclusion: MeHg caused motor impairment and spatial memory deficits that can be related with cerebral decrease in GPx and Na+/K+ ATPase activities and LPO production. Quercitrin (10mg/Kg) co-treatment confered neuroprotection mainly by conteracting the oxidative stress caused by MeHg, and by protecting Na+/K+ ATPase from inactivation by MeHg. Financially support: Capes, CNP