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Titolo:
Vitamin E succinate protects hepatocytes against the toxic effect of reactive oxygen species generated at mitochondrial complexes I and III by alkylating agents
Autore:
Zhang, JG; Nicholls-Grzemski, FA; Tirmenstein, MA; Fariss, MW;
Indirizzi:
Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, Pullman, WA 99164 USA Washington State Univ Pullman WA USA 99164 eut Sci, Pullman, WA 99164 USA
Titolo Testata:
CHEMICO-BIOLOGICAL INTERACTIONS
fascicolo: 3, volume: 138, anno: 2001,
pagine: 267 - 284
SICI:
0009-2797(200112)138:3<267:VESPHA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
TOCOPHERYL HEMISUCCINATE CYTOPROTECTION; METHANESULFONATE-INDUCED TOXICITY; CHEMICAL-INDUCED TOXICITY; LIPID-PEROXIDATION; PROBE 2',7'-DICHLOROFLUORESCIN; GLUTATHIONE DEPLETION; OXIDATIVE STRESS; RAT-LIVER; HYPOXIA; CALCIUM;
Keywords:
alpha-tocopheryl succinate; reactive oxygen species; mitochondrial electron transport chain; hepatocyte suspensions; ethyl methanesulfonate; alkylating agents; vitamin E;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Fariss, MW Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, Pullman, WA 99164 USA Washington State Univ Pullman WA USA 99164 llman, WA 99164 USA
Citazione:
J.G. Zhang et al., "Vitamin E succinate protects hepatocytes against the toxic effect of reactive oxygen species generated at mitochondrial complexes I and III by alkylating agents", CHEM-BIO IN, 138(3), 2001, pp. 267-284

Abstract

The mechanism of alpha -tocopheryl succinate (TS) cytoprotection against mitochondria-derived oxidative stress was investigated. Incubation of isolated rat hepatocytes with ethyl methanesulfonate (EMS), a mitochondrial alkylating toxicant caused mitochondrial dysfunction and necrotic cell death that was dependent on the production of reactive oxygen species (ROS) and lipid peroxidation. Mitochondria isolated from these cells showed a 3-fold increase in lipid hydroperoxides and a selective depletion of alpha -tocopherol(T), which preceded cell death. The pretreatment of hepatocytes with TS dramatically enriched cells and mitochondria with a-tocopherol and provided these membranes with complete protection against EMS-induced oxidative damage. TS pretreatment suppressed EMS-induced cellular ROS production, generated from mitochondrial complex I and III sites. In addition, the treatment with either rotenone (ROT, a complex I inhibitor) or antimycin A (AA, a complex III inhibitor) potentiated EMS-induced lipid peroxidation and necrotic cell death which were again completely prevented by TS treatment. Surprisingly, TS did not protect hepatocytes against thenoyltrifluoroacetone (TTFA), a complex II inhibitor-induced enhancement of EMS-induced toxic oxidative damage. We conclude that the inhibition of mitochondrial ROS production and lipid peroxidation by T released from TS, are the critical events responsible for TS-mediated cytoprotection against toxic oxidative stress derived from both mitochondrial complexes I and III. Our findings suggest that TS treatment may prove useful in combating diseases associated with mitochondrial-derived oxidative stress. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 21:02:52