Induction of metallothionein in the liver of carbon tetrachloride intoxicated rats: an immunohistochemical study

Metallothioneins (MTs), are low molecular weight proteins, mainly implicate d in metal ion detoxification. In the present study, we investigated the ex pression of hepatic MT in a rat model of injury and regeneration, induced b y carbon tetrachloride (CCI4) administration. A single intraperitoneal inje ction of 1 mi CCl4/kg body weight was performed in male Wistar rats, killed at different time points post-administration. The enzymatic activities of aspartate and alanine aminotransferases in serum were determined, in additi on to the liver histological findings, to estimate hepatotoxicity. The rate of tritiated thymidine incorporation into hepatic DNA, the enzymatic activ ity of thymidine kinase in liver tissue and the assessment of the mitotic i ndex in hepatocytes, were used as indices of regeneration. MT was detected immunohistochemically in liver tissue sections. CCl4 administration caused severe hepatic injury, followed by regeneration. MT expression became promi nent as early as 12 h after the administration of CCl4, in the nuclei of he patocytes, while at 24 and 36 h intense cytoplasmic staining for MT appeare d in the hepatocytes in the vicinity of necrotic areas. The peak of hepatoc yte proliferative capacity, occurring at 48 h post-CCl4 administration coin cides with the maximum nuclear and cytoplasmic MT expression. At further ti me points MT expression presented a decreasing trend. Induction of MT expre ssion was observed in the liver after a single administration of CCl4, bein g more prominent at the time of maximum hepatocellular proliferation, parti cipating actively in the replication of hepatocytes. (C) 2001 Elsevier Scie nce Ireland Ltd. All rights reserved.