2-Butoxyethanol autoprotection is due to resiliance of newly formed erythrocytes to hemolysis.
Pretreatment with a low dose of a toxic chemical protecting the animals from a subsequently administered lethal dose of the same chemical is called autoprotection. Autoprotection by model hepatotoxicants has been recently shown to be due to augmentation of cell division and tissue repair as well as an inherent resiliance of newly divided cells. The present studies were designed to investigate if an autoprotection model could be established in an extrahepatic tissue. The second objective was to test the hypothesis that inherent resiliance of newly divided cells is a major contributing mechanism for autoprotection. Female Sprague-Dawley rats (200-250 g) received a single administration of a moderately toxic but nonlethal dose (500 mg/kg, p.o.) 7 days prior to the administration of an LD90 dose (1500 mg/kg, p.o.) of the same compound. All rats receiving the initial protective dose are able to survive the lethal dose of butoxyethanol, in contrast to the death of those receiving the lethal dose alone. Following the administration of butoxyethanol, the hematocrit decreased from the normal 45% to 18% and by day 7, recovered to normal levels. Following the lethal challenge, hematocrit decreased to 13% in the naive rats, while decreasing only to 27% in rats receiving the protective dose, permitting animal survival. Administration of pyrazole to inhibit metabolism of butoxyethanol to butoxyacetic acid abolished autoprotection.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Pharmacology and Toxicology, College of Pharmacy and Health Sciences, Northeast Louisiana University, Monroe 71209-0470, USA.
D V
DV
Sivarao
H M
HM
Mehendale
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D001815:Bloodletting / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects*; D005026:Ethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D006461:Hemolysis / Q000187:drug effects*; D008136:Longevity / Q000187:drug effects; D011292:Premedication; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*
D005026:Ethylene Glycols; D011720:Pyrazoles; D012997:Solvents; C031280:pyrazole; D000444:Aldehyde Dehydrogenase; C017096:n-butoxyethanol