Potentiation of acrylate ester toxicity by prior treatment with the carboxylesterase inhibitor triorthotolyl phosphate (TOTP)

Silver, E.H.; Murphy, Sheldon D.

doi:10.1016/0041-008x(81)90281-7

Cited by 73 publications

(16 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the Hansch model, sigma electron distributions were calculated for the methacrylates as well as the net σ charges on the carbonyl carbon (Q σ ) in the regression analyses including the π-term 1) . On the adverse effects of acrylates, it was previously reported that inhaled acrylates caused sulfhydryl depression in the liver, lung, kidney, and blood 11) . In another study, Tanji and Hashimoto reported that acute oral toxicity (50％ lethal dose, LD50) in mice for acrylates, but not for methacrylates, was related to their reactivity with glutathione (GSH) in addition to the logarithm of octanol-water partition coefficient, log P 4) .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A structure-activity relationship study on the mechanisms of methacrylate-induced toxicity using NMR chemical shift of .BETA.-carbon, RP-HPLC log P and semiempirical molecular descriptor

Ishihara

Fujisawa

2009

Dent. Mater. J.

View full text Add to dashboard Cite

To clarify the mechanism of methacrylate-induced toxicity, a total of 24 acrylates, methacrylates, and dimethacrylates were chosen for a structure-activity relationship (SAR) study in terms of NMR chemical shifts, semiempirical molecular descriptors, and reverse phase (RP)-HPLC log P. Molecular descriptors as well as bulk, electronic, and energy descriptors were calculated using the PM3/CONFLEX method. A significant multiple linear regression equation for methacrylates in mice was denoted as log 1/LD50 (which was function [-(EHOMO+ELUMO)/2, log P]). Besides, significant linear regression equations for methacrylates were denoted as log 1/ED50 in HeLa S3 and in HGF cells as function [EHOMO and/or log P]. Results showed that the 13 C NMR chemical shift of β-carbon for methacrylates was correlated with their EHOMO. Findings of this study thus suggested that it might be possible to predict methacrylate-induced toxicity using physicochemical properties.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Computational chemistry has opened a new field for SAR research in toxicology 11,12) . Many SARs with quantum chemical descriptors have been reported for aquatic species 13) , and the SAR of estrogen-like bisphenol A analogs for breast cancer MCF-7 was reported previously using quantum chemical descriptors 14) .…”

Section: Introductionmentioning

confidence: 99%

A structure-activity relationship study on the mechanisms of methacrylate-induced toxicity using NMR chemical shift of .BETA.-carbon, RP-HPLC log P and semiempirical molecular descriptor

Ishihara

Fujisawa

2009

Dent. Mater. J.

View full text Add to dashboard Cite

show abstract

“…A previous study reported that ZP-AG is hydrolyzed by esterases (Smith et al, 1990b). TOTP, a nonselective esterase inhibitor, successfully inhibited esterase activity in mice and rats in vivo (Silver and Murphy, 1981;Kobayashi et al, 2012). In the present study, in addition to TOTP, BSO was used to reduce the GSH conjugation of ZP-AG.…”

Section: Discussionmentioning

confidence: 99%

“…It was reported that the plasma clearance of ZP-AG in the guinea pig was decreased by phenylmethylsulfonyl fluoride, a general esterase inhibitor, suggesting that ZP-AG is hydrolyzed by esterases (Smith et al, 1990b). In other reports, esterases were potently inhibited by tri-o-tolyl phosphate (TOTP), a nonselective esterase inhibitor, in mice and rats in vivo (Silver and Murphy, 1981;Kobayashi et al, 2012). ZP-AG conjugates with glutathione (GSH) in rat hepatocytes and bile (Grillo and Hua, 2003).…”

Section: Introductionmentioning

confidence: 99%

Zomepirac Acyl Glucuronide Is Responsible for Zomepirac-Induced Acute Kidney Injury in Mice

Iwamura

Watanabe

Akai

et al. 2016

Drug Metabolism and Disposition

View full text Add to dashboard Cite

Glucuronidation, an important phase II metabolic route, is generally considered to be a detoxification pathway. However, acyl glucuronides (AGs) have been implicated in the toxicity of carboxylic acid drugs due to their electrophilic reactivity. Zomepirac (ZP) was withdrawn from the market because of adverse effects such as renal toxicity. Although ZP is mainly metabolized to acyl glucuronide (ZP-AG) by UDP-glucuronosyltransferase, the role of ZP-AG in renal toxicity is unknown. In this study, we established a ZP-induced kidney injury mouse model by pretreatment with tri-o-tolyl phosphate (TOTP), a nonselective esterase inhibitor, and L-buthionine-(S,R)-sulfoximine (BSO), a glutathione synthesis inhibitor. The role of ZP-AG in renal toxicity was investigated using this model. The model showed significant increases in blood urea nitrogen (BUN) and creatinine (CRE), but not alanine aminotransferase. The ZP-AG concentrations were elevated by cotreatment with TOTP in the plasma and liver and especially in the kidney. The ZP-AG concentrations in the kidney correlated with values for BUN and CRE. Upon histopathological examination, vacuoles and infiltration of mononuclear cells were observed in the model mouse. In addition to immune-related responses, oxidative stress markers, such as the glutathione/ disulfide glutathione ratio and malondialdehyde levels, were different in the mouse model. The suppression of ZP-induced kidney injury by tempol, an antioxidant agent, suggested the involvement of oxidative stress in ZP-induced kidney injury. This is the first study to demonstrate that AG accumulation in the kidney by TOTP and BSO treatment could explain renal toxicity and to show the in vivo toxicological potential of AGs.

show abstract

“…The hydrolysis is catalyzed by the unspecific carboxylesterase [27,28] and can be inhibited with a carboxylesterase inhibitor, triorthotolyl phosphate (TOTP), which potentiates the acute toxicity of, e.g., inhaled methyl acrylate. The clinical effects of pretreatment of rats with TOTP before methyl acrylate exposure include more severe irritation of the nasal and ocular mucosa, reduced survival times and higher mortality [27]. Thus the esterase, which has been localized in the epithelial cells of the terminal bronchioli and alveoli by histochemical staining [29], is important for the hydrolysis of the inhaled substance.…”

Section: Metabolismmentioning

confidence: 99%

Methyl acrylate [MAK Value Documentation, 1993]

2012

The MAK‐Collection for Occupational Health and Safety

View full text Add to dashboard Cite

Published in the series Occupational Toxicants , Vol. 6 (1993) The article contains sections titled: Toxic Effects and Modes of Action Metabolism Effects in Man Effects on Animals Acute toxicity Skin irritation and corrosion Irritation of mucous membranes Skin sensitization Subacute and chronic toxicity Genotoxicity Carcinogenicity Manifesto (MAK value, classification)

show abstract

Potentiation of acrylate ester toxicity by prior treatment with the carboxylesterase inhibitor triorthotolyl phosphate (TOTP)

Cited by 73 publications

References 16 publications

A structure-activity relationship study on the mechanisms of methacrylate-induced toxicity using NMR chemical shift of .BETA.-carbon, RP-HPLC log P and semiempirical molecular descriptor

A structure-activity relationship study on the mechanisms of methacrylate-induced toxicity using NMR chemical shift of .BETA.-carbon, RP-HPLC log P and semiempirical molecular descriptor

Zomepirac Acyl Glucuronide Is Responsible for Zomepirac-Induced Acute Kidney Injury in Mice

Methyl acrylate [MAK Value Documentation, 1993]

Contact Info

Product

Resources

About