Metabolism of O,O,S-trimethyl phosphorothioate in rats after oral administration of a toxic dose, and the effect of coadministration of its antagonistic thionate isomer

Gray, Andrew; Fukuto, T. R.

doi:10.1016/0048-3575(84)90022-1

Cited by 15 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism of enhanced lipid peroxidation in the liver after treatment with 0 0 s -T M P is interesting and needs to be further studied. 0 0 0 -T M P antagonizes the lung injury which caused by 00s-TMP (Gray & Fukuto 1984) and also antagonizes enhancement of lipid peroxidation and increased oxidase activities in the lung caused by 00s-TMP. This coincidence supports the idea that lung injury was, at least partly, associated with lipid peroxidation following treatment with 00s-TMP, although their cause-effect relationship remains speculative.…”

Section: Discussionmentioning

confidence: 97%

“…In such conversion, metabolism of 00s-TMP is likely involved. 0 0 s -T M P undergoes -OCH3 demethylation or cleavage of -SCH3 in rats (Gray & Fukuto 1984). The latter is proposed to be an intoxication process, which may produce reactive intermediate [CH3S+] thorough sulphoxidation of the thiolosulpher (P-S-CH3) by cytochrome P-450-dependent mixed function oxidase (Nemery & Aldridge 1988a & b).…”

Section: Discussionmentioning

confidence: 99%

“…Studies on the mechanism of lung injury have shown that the ultimate toxicant is an activated intermediated metabolite but not the parent compound. This conclusion is based on the low activity of the parent compound and the effects on toxicity of pretreatment with substances affecting xenobiotic metabolism (Imamura & Hasegawa 1984;Gray & Fukuto 1984;Aldridge & Nemery 1984).…”

mentioning

confidence: 99%

“…The role of lipid peroxidation in lung injury was confirmed by investigating the antagonistic action of O,O,O-trimethyl phosphorothionate (000-TMP) towards 00s-TMP. 0 0 0 -T M P is known to be an antagonist of 00s-TMP not only in delayed death but also in lung injury (Umetsu et al 1979;Gray & Fukuto 1984) caused by the latter compound. Thus, changes caused by co-administration with 0 0 0 -T M P may indicate whether these changes are associated with the lung injury or not.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Enhanced Levels of Lipid Peroxidation and Xanthine Oxidase Activity in the Lung of Male Sprague‐Dawley Rats Following Treatment with O,O,S‐Trimethyl Phosphorothioate

Ohtaka

1994

Pharmacology & Toxicology

View full text Add to dashboard Cite

The purpose of this study was to investigate the roles of lipid peroxidation and a prototypical radical generating enzyme, xanthine oxidase, in lung injury caused by O,O,S-trimethyl phosphorothioate (OOS-TMP). Animals (five per group) were dosed with OOS-TMP at 40 mg/kg and sacrificed on the 1st, 3rd or 7th day after treatment. OOS-TMP increased lipid peroxidation (Mean +/- S.E.) to 139 +/- 9.6% of the control values in the lung and to 623 +/- 203% in the liver on the 1st day. When rats were dosed with OOS-TMP at 20, 40 and 60 mg/kg, lipid peroxidation in the lung and the liver were increased in a dose-dependent manner. In the lung, the total activity of xanthine oxidase was coincidentally increased. In contrast, the activities of superoxide dismutase and catalase were not affected. Effects of OOS-TMP on lipid peroxidation and the total activity of xanthine oxidase were completely abolished by coadministration with O,O,O-trimethyl phosphorothionate of a non-toxic dose (1 mg/kg), which antagonizes the lung injury after treatment with OOS-TMP. The present results indicate that free radical formation may be involved in lung injury after OOS-TMP treatment through activation of radical producing enzymes such as xanthine oxidase.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Enhanced Levels of Lipid Peroxidation and Xanthine Oxidase Activity in the Lung of Male Sprague‐Dawley Rats Following Treatment with O,O,S‐Trimethyl Phosphorothioate

Ohtaka

1994

Pharmacology & Toxicology

View full text Add to dashboard Cite

show abstract

“…O-and S-demethylation are prominent metabolic reactions for (MeO) 2 P(O)SMe in mice, but it is not known if this involves sulfoxidation or is catalyzed by GSH Stransferase (6). However, the prolonged persistence in this study of (MeO) 2 P(O)SMe in the presence of a small amount of (MeO) 2 P(S)SMe, as noted earlier with (MeO) 3 P-(S) (6), is more easily attributed to inhibition of cytochrome P450.…”

Section: Discussionmentioning

confidence: 99%

S-Methylation of O,O-Dialkyl Phosphorodithioic Acids: O,O,S-Trimethyl Phosphorodithioate and Phosphorothiolate as Metabolites of Dimethoate in Mice

Mahajna

Quistad

Casida

1996

Chem. Res. Toxicol.

View full text Add to dashboard Cite

O,O,S-Trimethyl phosphorodithioate and phosphorothiolate [(MeO)2P(S)SMe and (MeO)2P-(O)SMe, respectively are known from earlier studies to be impurities, delayed toxicants, and detoxication inhibitors in several major O,O-dimethyl phosphorodithioate insecticides. Our recent studies show extensive S-methylation of mono- and dithiocarbamic acids in mice, suggesting the possibility that phosphorodithioic acids such as (MeO)2P(S)SH might also undergo S-methylation. This possibility was examined in ip-treated mice with emphasis on the metabolites of dimethoate [(MeO)2P(S)SCH2C(O)NHMe], one of the most important organophosphorus insecticides. The urinary metabolites of dimethoate, which contains no P-SMe substituent, were found to include four compounds with P-SMe moieties identified by 31P NMR spectroscopy as MeO(HS)P(O)SMe, MeO(HO)P(O)SMe, (MeO)2P(S)SMe, and (MeO)2P-(O)SMe; the latter two compounds are also established by GC-MS as dimethoate metabolites in mouse urine, liver, kidney, and lung. Several approaches verified unequivocally that the previously unknown P-SMe metabolites in urine and tissues are due to in vivo S-methylation rather than to impurities. Studies with other O,O-dimethyl and O,O-diethyl phosphorodithioate insecticides established the analogous S-methylation pathway for ethion, malathion, phenthoate, phosalone, and phosmet in mice. Thus, metabolism of O,O-dialkyl phosphorodithioate insecticides in mammals is shown here for the first time to yield S-methyl phosphorodithioates and phosphorothiolates from in vivo S-methylation of the intermediate O,O-dialkyl phosphorodithioic acids.

show abstract

Kinetics of the atmospherically important gas-phase reactions of a series of trimethyl phosphorothioates

Goodman

Aschmann

Atkinson

et al. 1988

Arch. Environ. Contam. Toxicol.

View full text Add to dashboard Cite

Metabolism of O,O,S-trimethyl phosphorothioate in rats after oral administration of a toxic dose, and the effect of coadministration of its antagonistic thionate isomer

Cited by 15 publications

References 33 publications

Enhanced Levels of Lipid Peroxidation and Xanthine Oxidase Activity in the Lung of Male Sprague‐Dawley Rats Following Treatment with O,O,S‐Trimethyl Phosphorothioate

Enhanced Levels of Lipid Peroxidation and Xanthine Oxidase Activity in the Lung of Male Sprague‐Dawley Rats Following Treatment with O,O,S‐Trimethyl Phosphorothioate

S-Methylation of O,O-Dialkyl Phosphorodithioic Acids: O,O,S-Trimethyl Phosphorodithioate and Phosphorothiolate as Metabolites of Dimethoate in Mice

Kinetics of the atmospherically important gas-phase reactions of a series of trimethyl phosphorothioates

Contact Info

Product

Resources

About