The effect of glutathione monoethyl ester on the potentiation of the acute toxicity of methyl parathion, methyl paraoxon or fenitrothion by diethyl maleate in the mouse.
Depletion of hepatic glutathione in the mouse by pretreatment with diethyl maleate (DEM) is known to potentiate the acute toxicities of many dimethyl-substituted organothiophosphate insecticides. However, certain studies have raised doubts regarding the participation of glutathione in the detoxification of methyl parathion in the mouse, and hence the putative mechanism of action of DEM-induced potentiation of this insecticide. The present study evaluates the hypothesis that DEM potentiates the acute toxicities of methyl parathion, methyl paraoxon, and fenitrothion by a mechanism other than glutathione depletion. One hour following pretreatment of mice with DEM (0.75 ml/kg i.p.), glutathione was markedly depleted and the acute toxicities of methyl parathion, methyl paraoxon and fenitrothion were potentiated. Administration of glutathione monoethyl ester (20 mmol/kg p.o.) to DEM-pretreated mice attenuated DEM-depletion of hepatic glutathione, or maintained glutathione at or above control levels. However, glutathione monoethyl ester did not alter the DEM-induced potentiation of the lethality of these insecticides. Furthermore, administration of glutathione monoethyl ester to naive mice increased hepatic glutathione levels, but did not affect the percentage of animals succumbing to a challenge dose of methyl parathion, methyl paraoxon, or fenitrothion. These data indicate that DEM potentiates the toxicity of methyl parathion, methyl paraoxon or fenitrothion by a mechanism unrelated to hepatic glutathione content.
Sultatos
L G
LG
Department of Pharmacology and Toxicology, University of Medicine and Dentistry of New Jersey, Newark 07103-2757.
Huang
G J
GJ
Jackson
O
O
Reed
K
K
Soranno
T M
TM
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004357:Drug Synergism; D005278:Fenitrothion / Q000633:toxicity*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000494:pharmacology; D008743:Methyl Parathion / Q000633:toxicity*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010261:Paraoxon / Q000031:analogs & derivatives* / Q000633:toxicity
D008298:Maleates; D008743:Methyl Parathion; C042431:S-ethyl glutathione; C014476:diethyl maleate; D005978:Glutathione; D010261:Paraoxon; C008480:methylparaoxon; D005278:Fenitrothion