Liver metallothionein expression in thioacetamide-intoxicated rats

Metallothioneins (MT, a group of ubiquitous low molecular weight proteins, implicated primarily in metal ion detoxification, are known to be expressed during hepatocellular proliferation after partial hepatectomy ill rats. In the present study, we investigated the expression of MT in a rat model of liver injury and regeneration, induced by intraperitoneal administration of ee thioacetamide (TAA), The animals were killed at 0, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 hours after TAA administration. The rate of tritiat ed thymidine incorporation into hepatic DNA, the enzymatic activity of thym idine kinase, and the assessment of the mitotic index in hepatocytes were u sed as indices of liver regeneration. Liver MTs were detected immunohistoch emically. TAA administration caused severe hepatic injury, followed by rege neration, MT expression became prominent in hepatocytes as early as 12 hour s post-TAA administration, At 24 and 36 hours post-TAA administration inten se nuclear and cytoplasmic staining of hepatocytes was found in the vicinit y of necrotic areas. The maximal nuclear and cytoplasmic MT expression coin cides with the peak of hepatocyte proliferative capacity, occurring at 48 a nd 60 hours post-TAA administration. MT expression correlated positively wi th the Zn content of liver tissue, but negatively with serum one, at the ti me of maximum hepatocyte proliferative capacity. This study suggests that M T participates in hepatocyte replication after toxin-induced liver injury.