Effects of sulfhydryl modulation on ethyl acrylate-induced forestomach toxicity.
Acute administration of a single dose of ethyl acrylate (EA) to F344 rats by gavage caused time- and dose-dependent forestomach edema. Evidence from our laboratory and others suggested that EA is hydrolyzed to acrylic acid (AA) and ethanol both in vivo and in vitro. The major metabolites detected in teh urine of rats treated with EA were derivatives of the glutathione conjugates of EA and AA. The current work was undertaken to investigate the effects of sulfhydryl-depleting agents (diethylmaleate and fasting) and sulfhydryl-containing agents (cysteine and cysteamine) on EA-induced forestomach edema. Results presented in this report revealed that pretreatment of rats with sulfhydryl-containing chemicals such as cysteine or cysteamine has potentiated EA-induced forestomach edema. In contrast, depletion of indigenous sulfhydryls by fasting of rats or pretreatment with diethylmaleate (DEM) protected against EA-induced forestomach edema. Furthermore, repetitive daily administration of EA by gavage induced mucosal forestomach hyperplasia. Co-administration of cysteamine and EA resulted in a significant enhancement of the severity of EA-induced forestomach mucosal hyperplasia. In conclusion, current data suggest that modulation of indigenous sulfhydryls play a role in EA-induced forestomach toxicity; however, the exact mechanism underlying this role remains to be characterized.
Ghanayem
B I
BI
National Institute of Environmental Health Sciences, Research Triangle Park, NC.
Maronpot
R R
RR
Matthews
H B
HB
D000179:Acrylates / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D003543:Cysteamine / Q000494:pharmacology*; D003545:Cysteine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced*; D005215:Fasting; D008297:Male; D008298:Maleates / Q000494:pharmacology; D009153:Mutagens / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013272:Stomach Diseases / Q000139:chemically induced* / Q000517:prevention & control
D000179:Acrylates; D008298:Maleates; D009153:Mutagens; D003543:Cysteamine; C040833:ethyl acrylate; C014476:diethyl maleate; D003545:Cysteine