Effect of hepatic stimulator substance (HSS) on cadmium-induced acute hepatotoxicity in the rat liver.

The hepatoprotective effect of HSS against cadmium-induced liver injury was investigated. Rats were intoxicated with a dose of cadmium (3.5 mg/kg b.w.). The rats were treated with normal saline (group I) or HSS (100 mg protein/kg b.w.; group II) 2 hr later and killed at different time points. Hematoxylin-eosin (HE) sections were assessed for necrosis, apoptosis, peliosis, mitoses, and inflammatory infiltration. Serum enzyme activities were assayed. Apoptosis was quantified by the Tunel technique. Thymidine kinase activity and the rate of [3H]thymidine incorporation into DNA were also assayed. Necrosis, hepatocyte apoptosis, and peliosis were minimized in HSS-treated rats (group II). Nonparenchymal cell apoptosis and liver regeneration were not quantitively altered in the HSS-treated group, though the time profile was different. HSS protects hepatocytes against cadmium-induced necrosis, apoptosis, and peliosis. Apoptosis was the major type of cell death for nonparenchymal liver cells and strongly correlated with the extent of peliosis. Interactions between hepatocytes and nonparenchymal liver cells seem to be important for the genesis of hepatic trauma in acute cadmium hepatotoxicity.