Experimental toxic liver damage and hepatic plasma clearance of 99mTc-mebrofenin (iminodiacetate derivative). III. Chronic CCl4-induced liver damage with eventual cirrhosis in rabbits.

Chronic damage to liver parenchyma was induced in rabbits by the long-term administration of carbon tetrachloride. The animals were serially sacrificed 3, 6 and 9 months after the start of intoxication, and examined histopathologically. The biological response was qualitatively assessed from results of histological studies, and measured utilizing series of typical biochemical indices of liver damage, 99mTc-mebrofenin (an-IDA-derivative) plasma clearance by the liver, and quantified indices of uptake and organ transfer of the compound. It was found that the plasma clearance and transfer parameters show association with chronic liver damage. The reduction of plasma 99mTc-mebrofenin clearance in intoxicated rabbits was also associated with changes in the biochemical indices of liver function and damage.

Experimental toxic liver damage and hepatic plasma clearance of 99mTc-mebrofenin (iminodiacetate derivative). I. Early, acute CCl4-induced liver damage in rabbits.

Liver damage was induced in rabbits by graded doses of carbon tetrachloride. The damage was assessed by means of quantitative morphometry using necrosis and steatosis of the parenchyma as end points. Biological response was measured utilizing a series of typical biochemical indices of liver damage as well as plasma clearance by the liver 99mTc-mebrofenin (an IDA derivative) and quantified indices of uptake and organ transfer of the compound. No correlation was found between the CCl4 dose and its effect (i.e. degree of necrosis and steatosis of liver). However, a very strong negative correlation was found between the degree of necrosis in individual animals and value of the clearance. The extent of the damage was positively correlated with liver transfer rate of 99mTc-MBF. Plasma activity of ALAT, TG, GGTP and AspAT were higher in the poisoned animals, however, only increments of activity of GGTP, ALAT and LDH showed statistically significant correlation with the individually assessed damage (necrosis).

Experimental toxic liver damage and hepatic plasma clearance of 99mTc-mebrofenin (iminodiacetate derivative). II. Recovery from the acute, CCl4-induced liver damage.

Liver parenchyma damage was induced in rabbits by the administration of carbon tetrachloride. The animals were serially sacrificed 3, 10, 17 and 31 days post intoxication and examined morphometrically for the extent of necrosis, steatosis and balloon degeneration of hepatocytes. Biochemical indices of the liver damage were studied as well as hepatic clearance of blood plasma from Tc-99m complex of an IDA derivative Tc99m complex (99mTc-mebrofenin--99mTc-MBF) and its uptake and liver transfer characterizing parameters. It was found that toxic effects of CCl4 were conspicuous up to 10 days after administration of carbon tetrachloride. In that period elevated activity of AspAT, ALAT, GGTP and elevated cholesterol and triglycerides were found in the plasma. As in the first paper of this series of works there has been a highly significant statistical association between the Tc-MBF plasma clearance, the uptake and liver transfer of the compound and parenchyma damage in the organ.