Glutathione depletion in rat hepatocytes:: a mixture toxicity study with α,β-unsaturated esters

被引:21
作者
Freidig, A [1 ]
Hofhuis, M [1 ]
Van Holstijn, I [1 ]
Hermens, J [1 ]
机构
[1] TNO, Nutr & Food Res, Div Explanatory Toxicol, NL-3700 AJ Zeist, Netherlands
关键词
D O I
10.1080/00498250110052733
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1. Glutathione (GSH) depletion is often reported as an early cytotoxic effect, caused by many reactive organic chemicals. In the present study, GSH depletion in primary rat hepatocytes was used as an in vitro effect-equivalent to measure the toxic potency of alpha,beta -unsaturated esters (acrylates and methacrylates). 2. When these compounds were administered as a mixture, GSH depletion was dose additive. The result of the mixture study shows that GSH depletion may be a useful effect-equivalent for the risk assessment of mixtures of alpha,beta -unsaturated esters. 3. To get more insight in the underlying mechanisms of GSH depletion, the metabolism of two esters was investigated in greater detail. One of them, allyl methacrylate, was metabolized to acrolein. This metabolic pathway can explain the high potency of allyl methacrylate to deplete GSH despite its low intrinsic chemical reactivity.
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收藏
页码:295 / 307
页数:13
相关论文
共 56 条
[1]  
BADR MZ, 1986, J PHARMACOL EXP THER, V238, P1138
[2]  
BELINSKY SA, 1986, J PHARMACOL EXP THER, V238, P1132
[3]  
Bergmeyer H.-U., 1965, Methods of Enzymatic Analysis, P736
[4]  
BOYLAND E, 1969, BIOCHEM PHARMACOL, V19, P1526
[5]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[6]   CALCULATION OF ACUTE TOXICITY OF MIXTURES OF POISONS TO RAINBOW TROUT [J].
BROWN, VM .
WATER RESEARCH, 1968, 2 (10) :723-&
[7]   Regulating and assessing risks of cholinesterase-inhibiting pesticides: Divergent approaches and interpretations [J].
Carlock, LL ;
Chen, WL ;
Cordon, EB ;
Killeen, JC ;
Manley, A ;
Meyer, LS ;
Mullin, LS ;
Pendino, KJ ;
Percy, A ;
Sargent, DE ;
Seaman, LR ;
Svanborg, NK ;
Stanton, RH ;
Van Goethem, IL .
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS, 1999, 2 (02) :105-160
[8]   Acrylic acid induces the glutathione-independent mitochondrial permeability transition in vitro [J].
Custodio, JBA ;
Palmeira, CM ;
Moreno, AJ ;
Wallace, KB .
TOXICOLOGICAL SCIENCES, 1998, 43 (01) :19-27
[9]   IDENTIFICATION OF URINARY MERCAPTURIC ACIDS FORMED FROM ACRYLATE, METHACRYLATE AND CROTONATE IN THE RAT [J].
DELBRESSINE, LPC ;
SEUTTERBERLAGE, F ;
SEUTTER, E .
XENOBIOTICA, 1981, 11 (04) :241-247
[10]   Simultaneous determination of eight lipid peroxidation degradation products in urine of rats treated with carbon tetrachloride using gas chromatography with electron-capture detection [J].
DeZwart, LL ;
Venhorst, J ;
Groot, M ;
Commandeur, JNM ;
Hermanns, RCA ;
Meerman, JHM ;
VanBaar, BLM ;
Vermeulen, PE .
JOURNAL OF CHROMATOGRAPHY B, 1997, 694 (02) :277-287