Assessment of Hepatic Indicators of Subchronic Carbon Tetrachloride Injury and Recovery in Rats

Assessment of Hepatic Indicators of Subchronic Carbon TetrachlorideInjury and Recovery in Rats. ALLIS, J. W., WARD, T. R., SEELY,J. C, and SIMMONS, J. E. (1990). Fundam Appl. Toxicol. 15, 558–570.To determine the course of hepatic recovery from subchronicoral administration of carbon tetrachloride (CCl₄), male F-344rats were gavaged with 0, 20, or 40 mg CCl₄/kg, 5 days/week,for 12 weeks. Exposure to CCl₄ caused dosage-dependent increasesin 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 hepaticcytochrome P450. Centrilobular hepatocellular vacuolar degeneration,necrosis, and cirrhosis occurred at both 20 and 40 mg/kg, withdosage-dependent severity. Reversibility of these reported effectsvaried with parameter. By Day 8 postexposure, necrosis had disappearedand all serum indicators and cytochrome P450 had returned tocontrol levels. By Day 15 postexposure, the severity of thevacuolar degeneration had decreased. Reversibility of cirrhosiswas dosage dependent; complete recovery occurred in the low-but not the high-dose group by Day 15. The disappearance ofthe increase in relative liver weight was also dependent ondosage; the low- but not the high-dose group had returned tothe control level by Day 22. In an attempt to measure persistenthepatic damage, liver uptake relative to the spleen was determinedfor a sulfur colloid labeled with technetium-99m and for tritiated2-deoxyglucose. Neither method consistently measured hepaticdamage in cirrhotic livers due, in part, to the high degreeof variability in the tracer uptake data.