Metallothionein and heat shock protein expression during acute liver injury and regeneration in rats

Metallothioneins (MT) are cytosolic proteins rich in cysteine which play a physiological role in metal ion homeostasis. Heat shock proteins (HSPs) are expressed in various organs in response to different stress stimuli. The p urpose of the present study was to examine the intrahepatic distribution of MT and HSP-27, -70 and -90 in two different experimental models of acute l iver injury and regeneration, induced by either thioacetamide, or carbon te trachloride administration in male Wistar rats. Toxicological endpoints and markers of hepatocellular regeneration were assessed at various time point s following toxin administration. The enzymatic activities of aspartate and alanine aminotransferases in serum, and histological findings in the liver were used to estimate toxin-induced injury. Tritiated thymidine incorporat ion into hepatic DNA, liver thymidine kinase activity and hepatocyte mitoti c index were used to estimate liver regeneration. MT and HSPs were detected immunohistochemically. At the time of maximum liver injury, moderate MT an d intense HSPs expression was prominent in hepatocytes in the vicinity of n ecrotic areas. At the time of maximum hepatocellular proliferation, intense MT and HSP-90 staining was evident in all hepatocytes, while at the same t ime, mild HSP-27 and HSP-70 immunoreactivity was noted. Our findings indica te that the differential distribution of MT and HSPs in the liver after tox in-induced injury, in common with the observed pattern of staining, reflect liver proliferating capacity.