Attenuation by methyl mercury and mercuric sulfide of pentobarbital induced hypnotic tolerance in mice through inhibition of ATPase activities and nitric oxide production in cerebral cortex

Abstract

This study is aimed at exploring the possible mechanism of hypnosis-enhancing effect of HgS or cinnabar (a traditional Chinese medicine containing more than 95% HgS) in mice treated with pentobarbital. We also examined whether the effect of HgS is different from that of the well-known methyl mercury (MeHg). After a short period (7 days) of oral administration to mice, a nontoxic dose (0.1 g/kg) of HgS not only significantly enhanced pentobarbital-induced hypnosis but also attenuated tolerance induction; while a higher dose (1 g/kg) of HgS or cinnabar exerted an almost irreversible enhancing effect on pentobarbital-hypnosis similar to that of MeHg (2 mg/kg) tested, which was still effective even after 10 or 35 days cessation of administration. To study comparatively the effects of different mercury forms from oral administration of MeHg and HgS on membrane ATPase activities of experimental mice, analysis of the Hg content in the cerebral cortex revealed that correlated with the decrease of Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities. Furthermore, NO levels of blood but not that of cerebral cortex were also decreased by mercuric compounds. Although pentobarbital alone enhanced cytochrome p450-2C9 in time dependent manner, all of mercurial compounds tested had no such effect. All of these findings indicated that the mercurial compounds including cinnabar, HgS and MeHg exert a long-lasting enhancing hypnotic activity without affecting pentobarbital metabolism, which provides evidence-based sedative effect of cinnabar used in Chinese traditional medicine for more than 2,000 years. The nontoxic HgS dosing (0.1 g/kg/day) for consecutive 7 days is perhaps useful for delaying or preventing pentobarbital-tolerance.

Alpha-lipoic acid reduces methylmercury-induced neuronal injury in rat cerebral cortex via antioxidation pathways

“…In addition, MeHg would increase Ca 2+ influx into neurons, followed by leading to Ca 2+ overload, depolarization of mitochondria membrane potential, and ROS generation. Moreover, as ROS formation could disrupt electron transport and ATP synthesis (Chuu et al, ), the Ca 2+ ‐ATPase activity, an important enzyme in maintaining intracellular Ca 2+ homeostasis, would be inhibited by ROS overproduction, which may aggravate the intracellular Ca 2+ overload. Our previous studies reported that MeHg‐induced high Glu concentrations, causing hyper‐activation of NMDARs, resulted in Ca 2+ dyshomeostasis, which aggravated neuron damage (Petroni et al, ; Liu et al, ; Yang et al, ).…”

Evaluation of GlutathioneS-transferaseGSTM1andGSTT1Polymorphisms and Methylmercury Metabolism in an Exposed Amazon Population

“…Mercury (Hg) is one of the most hazardous metals in the environment, and metalmediated toxicity involves oxidative damage to macromolecules (Beyersmann and Hartwig 2008;Chuu et al 2008;Mori et al 2007). Several experimental and epidemiological studies demonstrated that exposure to Hg in its organic form, methylmercury (MeHg), which is found in fish and other seafood, is associated with neurotoxic effects (Counter et al 2002;Dolbec et al 2000), damage to the immune and renal system Rutowski et al 1998), infertility (Boujbiha et al 2009), cardiovascular diseases (Virtanen et al 2007), and cancer (IARC 1993).…”

Civa II Klorürün Sıçan Beyin Dokusunda Oluşturduğu Toksisiteye Karşı Borik Asidin Koruyucu Etkisinin İncelenmesi

“…Organic forms are generally more toxic, while inorganic forms are more abundant in the environment [38]. One of the main mechanisms responsible for HgCl2 toxicity is oxidative stress [39][40][41]. Oxidative stress can trigger a protective antioxidant system that avoids or ameliorates neuro toxicity in the brain [32].…”