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Titolo:
METABOLIC ALTERATIONS IN HEPATOCYTES PROMOTED BY THE HERBICIDES PARAQUAT, DINOSEB AND 2,4-D
Autore:
PALMEIRA CM; MORENO AJ; MADEIRA VMC;
Indirizzi:
UNIV COIMBRA,DEPT ZOOL P-3049 COIMBRA PORTUGAL UNIV COIMBRA,DEPT BIOCHEM P-3049 COIMBRA PORTUGAL
Titolo Testata:
Archives of toxicology
fascicolo: 1, volume: 68, anno: 1994,
pagine: 24 - 31
SICI:
0340-5761(1994)68:1<24:MAIHPB>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
ISOLATED RAT HEPATOCYTES; LIPID-PEROXIDATION; CELL-DEATH; GLUTATHIONE DEPLETION; INDUCED CYTOTOXICITY; CALCIUM HOMEOSTASIS; OXIDATIVE STRESS; CYTO-TOXICITY; FREE CA-2+; MECHANISM;
Keywords:
HERBICIDE; NADH; GLUTATHIONE; HEPATOCYTE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
48
Recensione:
Indirizzi per estratti:
Citazione:
C.M. Palmeira et al., "METABOLIC ALTERATIONS IN HEPATOCYTES PROMOTED BY THE HERBICIDES PARAQUAT, DINOSEB AND 2,4-D", Archives of toxicology, 68(1), 1994, pp. 24-31

Abstract

The cytotoxic effects of the herbicides paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride), dinoseb (2-sec-butyl-4,6-dinitrophenol) and 2,4-D (2,4-dichlorophenoxyacetic acid) on freshly isolated rat hepatocytes were investigated. Paraquat and 2,4-D (1-10 mM) caused a dose andtime dependent cell death accompanied by depletion of intracellular glutathione (GSH) and mirroring increase of oxidized glutathione (GSSG). Dinoseb, the most effective cytotoxic compound under study (used in concentrations 1000 fold lower than paraquat and 2,4-D), exhibited moderate effects upon the level of GSH and GSSG. These limited effects are at variance with significant effects upon the adenine and pyridine nucleotide contents. ATP and NADH levels are rapidly depleted by herbicide metabolism. This depletion is observed in the millimolar range forparaquat and 2,4-D and in the micromolar range for dinoseb. 2,4-D completely depletes cellular ATP, with subsequent cell death, as detectedby LDH leakage. Paraquat rapidly depletes NADH, according to the redox cycling of the herbicide metabolism. The most effective compound is dinoseb since it exerts similar effects as described for paraquat and 2,4-D at concentrations 1000 fold lower. Simultaneously with NADH and ATP depletion, the levels of ADP, AMP and NAD+ increase in hepatocytesincubated in the presence of the herbicides. In contrast to NADH, thetime course and extent of ATP depletion and fall in energy charge correlate reasonably with the time of onset and rate of cell death. It isconcluded that the herbicides, paraquat and 2,4-D are hepatotoxic andinitiate the process of cell death by decreasing cellular GSH. As a consequence of this primary disturbance, alteration of adenine and pyridine nucleotides contents is a critical event in the induction of irreversible cell injury.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 09:25:09