ISSN:
1432-0738
Keywords:
Key words Autoprotection
;
Bled/recovered
;
2-Butoxyacetic acid
;
2-Butoxyethanol
;
Ethylene glycol monobutyl ether
;
Hematocrit
;
Hematopoiesis
;
Hematotoxicity
;
Packed cell volume
;
Pyrazole
;
Red blood cells
;
Resiliance
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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. A time-course study, wherein the time intervening between the protective and lethal dose of butoxyethanol was increased, indicated that 100% autoprotection observed at 7 days wanes to a mere 12%by day 21, suggesting that ageing of the newly formed cells results in loss of their resiliance to hemolysis. This was also confirmed by in vitro studies. To test the hypothesis that new blood cells that replace the hemolyzed cells form the basis of autoprotection, rats were bled and allowed to recover prior to challenge with a lethal dose of butoxyethanol. Bled/recovered rats demonstrated an 87% survival. In vitro incubation experiments revealed that the red blood cells from the bled/recovered rats were resilient to a 10-fold range of butoxyacetic acid concentration compared to cells from control rats. This work has led to the establishment of 2-butoxyethanol autoprotection model in an extrahepatic tissue. The mechanism of this autoprotection seems to be the inherent resiliance of newly formed red blood cells that replace the cells lost due to hemolysis caused by the protective dose.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002040050207
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