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Titolo:
Antioxidant compounds and Ca2+ pathway blockers differentially protect against methylmercury and mercuric chloride neurotoxicity
Autore:
Gasso, S; Cristofol, RM; Selema, G; Rosa, R; Rodriguez-Farre, E; Sanfeliu, C;
Indirizzi:
CSIC, Inst Invest Biomed Barcelona, Dept Pharmacol & Toxicol, IDIBAPS, E-08036 Barcelona, Spain CSIC Barcelona Spain E-08036 Toxicol, IDIBAPS, E-08036 Barcelona, Spain
Titolo Testata:
JOURNAL OF NEUROSCIENCE RESEARCH
fascicolo: 1, volume: 66, anno: 2001,
pagine: 135 - 145
SICI:
0360-4012(20011001)66:1<135:ACACPB>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
CEREBELLAR GRANULE CELLS; METHYL MERCURY; INTRACELLULAR CA2+; OXIDATIVE STRESS; INDUCED CYTOTOXICITY; INORGANIC MERCURY; NERVOUS-SYSTEM; IN-VITRO; NEURONS; RAT;
Keywords:
neuronal cultures; neuroprotection; oxidative stress; Ca2+ homeostasis; mercury;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Sanfeliu, C CSIC, Inst Invest Biomed Barcelona, Dept Pharmacol & Toxicol, IDIBAPS, Rossello 161,6th Floor, E-08036 Barcelona, Spain CSIC Rossello 161,6th Floor Barcelona Spain E-08036 na, Spain
Citazione:
S. Gasso et al., "Antioxidant compounds and Ca2+ pathway blockers differentially protect against methylmercury and mercuric chloride neurotoxicity", J NEUROSC R, 66(1), 2001, pp. 135-145

Abstract

The effects of the environmental contaminants methylmercury (MeHg) and inorganic mercury (HgCl2) on cell viability, intracellular calcium concentration ([Ca2+](i)), and reactive oxygen species (ROS) generation were studied in rat cerebellar granule neuron cultures using fluorescent methods. MeHg exhibited an LC50 (2.47 [LM) tenfold lower than that of HgCl2 (26.40 muM). Tostudy the involvement of oxidative stress and Ca2+ homeostasis disruption in mercury-induced cytotoxicity, we tested the neuroprotective effects of several agents that selectively interfere with these mechanisms. After a 24 hr exposure, the cytotoxic effect of both mercury compounds was reduced by thapsigargin, an inhibitor of endoplasmic reticulum Ca2+-ATPase; the Ca2+ channel blocker flunarizine; and the Na+/Ca2+ exchanger blocker benzamil. All these compounds decreased the mercury-mediated [Ca2+](i) rise. These results indicate that Ca2+ influx through Ca2+ channels and the Na+/Ca2+ exchanger and Ca2+ mobilization from the endoplasmic reticulum are involved in mercury-mediated cytotoxicity. The antioxidants probucol and propyl gallate reduced the HgCl2 toxicity. Probucol and vitamin E partially inhibited the MeHg toxicity after a 24 hr period, whereas propyl gallate completely prevented this effect. Probucol slightly reduced ROS generation in methylmercury-exposed cultures and decreased mercury-mediated rise of [Ca2+](i). Propyl gallate abolished ROS generation and partially inhibited the increase of [Ca2+](i) induced by both mercury compounds. Propyl gallate also protected human cerebral cortical neuron cultures from the MeHg effect even after 72 hr of MeHg exposure, thus showing a longlasting effect. Our data suggest that disruption of redox equilibrium and Ca2+ homeostasis contribute equally to HgCl2-mediated toxicity, whereas oxidative stress is the main cause of MeHgneurotoxicity. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 07:01:00