Hepatocellular regeneration: key to thioacetamide autoprotection.
Low doses of thioacetamide stimulate cell division and tissue repair in the liver. The objective of this study was to develop an autoprotection model for thioacetamide and investigate if a low dose of thioacetamide (50 mg/kg orally) protects against lethality of a subsequently administered lethal dose (400 mg/kg orally) of the same compound. The extent of cell division was investigated to test if autoprotection results from augmented tissue repair and recovery from injury rather than decreased injury itself. After a single administration of the protective dose of thioacetamide, hepatocellular nuclear DNA synthesis as measured by 3H-thymidine incorporation into hepatocellular nuclear DNA peaked at 36 hr indicating maximum level of S-phase stimulation. Pretreatment with the antimitotic colchicine abolished autoprotection and this was associated with a significantly decreased 3H-thymidine incorporation. Preadministration of the protective dose of thioacetamide did not result in an altered infliction of injury from the subsequently administered lethal dose. Colchicine intervention in the autoprotected group resulted in injury that followed a pattern similar to the group that received the high dose alone, ultimately resulting in animal death. These findings suggest that cell division stimulated by the protective low dose of thioacetamide is the critical mechanism in thioacetamide autoprotection.
Mangipudy
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RS
Division of Pharmacology and Toxicology, School of Pharmacy and Allied Health Sciences, Northeast Louisiana University, Monroe 71209-0470, USA.
Chanda
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Mehendale
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HM
D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D003078:Colchicine / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D006074:Gout Suppressants / Q000633:toxicity; D007553:Isotope Labeling; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000293:injuries; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D002273:Carcinogens; D006074:Gout Suppressants; D013853:Thioacetamide; D014316:Tritium; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D003078:Colchicine; D013936:Thymidine