Haloperidol Cytotoxicity and Its Relation to Oxidative Stress

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Publikace nespadá pod Filozofickou fakultu, ale pod Lékařskou fakultu. Oficiální stránka publikace je na webu muni.cz.
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RAUDENSKÁ Martina GUMULEC Jaromír BABULA Petr STRAČINA Tibor SZTALMACHOVÁ Markéta POLANSKÁ Hana ADAM Vojtech KIZEK Rene NOVÁKOVÁ Marie MASAŘÍK Michal

Rok publikování 2013
Druh Článek v odborném periodiku
Časopis / Zdroj MINI-REVIEWS IN MEDICINAL CHEMISTRY
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Doi http://dx.doi.org/10.2174/13895575113136660100
Obor Fyziologie
Klíčová slova Arrhytmia; cardiotoxicity; dopamine; haloperidol; oxidative stress; Torsade de Pointes
Popis Haloperidol (HP) is used for the symptomatic treatment of psychosis, manic phases, hyperactivity, aggressiveness, and acute delirium. Long-term use leads to various adverse side effects, especially to severe impairment of extrapyramidal nerve tracts and in particular, altered QT interval and increased incidence of arrhytmias. It is believed that cytotoxicity of HP and its metabolites is responsible for both neurotoxicity and cardiotoxicity. Extrapyramidal and cardiac adverse side effects may be explained by the HP-induced oxidative stress, as implicated by many studies. HP was reported to induce lipid peroxidation with subsequent membrane changes, responsible for cell death. Vice versa, cells resistant to oxidative stress are also resistant to the toxic effects of HP. Similarly, high percentage of patients suffering from extrapyramidal symptoms treated by vitamin E and other lipid-soluble antioxidants demonstrates diminishing of these adverse side effects. HP’s ability to induce oxidative stress by multi-modal action (increased metabolism of dopamine, decrease of glutathione content, induction of NF-B transcription factor, and inhibition of complex I of respiratory chain) has been established just recently. This review brings summarizing view on the cytotoxicity of haloperidol and involvement of reactive oxygen species and oxidative stress HP-induced cytotoxicity.
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