Assessment of hepatic indicators of subchronic carbon tetrachloride injury and recovery in rats.
To determine the course of hepatic recovery from subchronic oral administration of carbon tetrachloride (CCl4), male F-344 rats were gavaged with 0, 20, or 40 mg CCl4/kg, 5 days/week, for 12 weeks. Exposure to CCl4 caused dosage-dependent increases in relative liver weight and the serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, and cholesterol as well as a dosage-dependent decrease in hepatic cytochrome P450. Centrilobular hepatocellular vacuolar degeneration, necrosis, and cirrhosis occurred at both 20 and 40 mg/kg, with dosage-dependent severity. Reversibility of these reported effects varied with parameter. By Day 8 postexposure, necrosis had disappeared and all serum indicators and cytochrome P450 had returned to control levels. By Day 15 postexposure, the severity of the vacuolar degeneration had decreased. Reversibility of cirrhosis was dosage dependent; complete recovery occurred in the low- but not the high-dose group by Day 15. The disappearance of the increase in relative liver weight was also dependent on dosage; the low- but not the high-dose group had returned to the control level by Day 22. In an attempt to measure persistent hepatic damage, liver uptake relative to the spleen was determined for a sulfur colloid labeled with technetium-99m and for tritiated 2-deoxyglucose. Neither method consistently measured hepatic damage in cirrhotic livers due, in part, to the high degree of variability in the tracer uptake data.
Allis
J W
JW
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Ward
T R
TR
Seely
J C
JC
Simmons
J E
JE
D000818:Animals; D001693:Biological Transport, Active; D001835:Body Weight / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity*; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D003847:Deoxyglucose; D002251:Carbon Tetrachloride