Time course of hepatic injury and recovery following coadministration of carbon tetrachloride and trichloroethylene in Fischer-344 rats.
Simultaneous administration of trichloroethylene (TCE), at an oral dose of 0.5 ml/kg, resulted in a marked potentiation of liver injury caused by an oral dose of carbon tetrachloride (CCl4, 0.05 ml/kg). Hepatic glutathione levels were depressed at 24 hr only in the rats given TCE and CCl4. Using serum enzyme (ALT and SDH) as indicators of hepatotoxicity, potentiation of CCl4-injury was most apparent at 24 hr. Upon histological examination of H&E stained liver sections, the differences between livers obtained from TCE and CCl4-treated rats versus CCl4-treated rats were most apparent at later time points (48 and 72 hr). At 48 hr after CCl4, livers showed a distinctive and uniform pattern of injury with regeneration features predominating over necrosis. At this time, livers from TCE and CCl4-treated rats were characterized by extensive zone 3 coagulative necrosis. Inflammatory infiltrations were less prominent. At 72 hr, morphological features of livers from TCE and CCl4 rats were similar to those from rats given CCl4 alone at 48 hr. From the results obtained, it appears that the regenerative activity of the liver may be delayed in rats simultaneously administered TCE and CCl4 as compared to rats administered only CCl4.
Steup
D R
DR
Department of Pharmacology and Toxicology, University of Arizona, College of Pharmacy, Tucson 85721.
Hall
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P
McMillan
D A
DA
Sipes
I G
IG
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D007064:L-Iditol 2-Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014241:Trichloroethylene / Q000633:toxicity*
D014241:Trichloroethylene; D007064:L-Iditol 2-Dehydrogenase; D000410:Alanine Transaminase; D005978:Glutathione