Peliosis hepatis: microscopic and macroscopic type, time pattern, and correlation with liver cell apoptosis in a model of toxic liver injury.

Macroscopic and microscopic types of peliosis hepatis, time pattern, and correlation with hepatocyte and sinusoidal cell apoptosis were investigated. Male Wistar rats were injected with a dose of cadmium (6.5 mg CdCl(2)/kg body weight, intraperitoneally; group I). Putrescine (300 micromol/kg body weight, intraperitoneally; group II) was injected at 2, 5, and 8 hours and vascular endothelial growth factor (VEGF; 400 ng/animal, intravenously; group III) at 2 hours. Animals from each group were humanely killed 0, 6, 12, 24, 48, or 60 hours after cadmium intoxication. Liver tissue was histologically assessed for necrosis, apoptosis, and peliosis. Apoptosis was also quantified by the TUNEL assay for hepatocytes and nonparenchymal liver cells. The discrimination between hepatic cell subpopulations was done histochemically. Sinusoidal cell apoptosis and macroscopic peliosis hepatis evolved in a monophasic pattern and correlated closely. Putrescine or VEGF administration totally reversed macroscopic peliosis. Putrescine exerted a major protective effect on hepatocytes, whereas the protective effect of VEGF was more pronounced for nonparenchymal liver cells. Microscopic peliosis also evolved in a monophasic pattern preceding macroscopic type. The extent of the lesion was reduced by putrescine and almost totally reversed by VEGF. Macroscopic peliosis progresses as a compound lesion closely correlating with nonparenchymal cell apoptosis. Both hepatocyte and nonparenchymal cell injury are prerequisites for the genesis of the lesion. Microscopic peliosis precedes macroscopic peliosis and up to a degree seems to be independent of initial hepatocyte injury, but it seems to depend on nonparenchymal cell injury.

The hepatoprotective effect of putrescine against cadmium-induced acute liver injury.

The hepatoprotective effect of putrescine against cadmium liver injury was investigated. Male Wistar rats were injected with a dose of cadmium (6.5 mg CdCl(2)/kg bodyweight, intraperitoneally). Normal saline (group I) or putrescine (300 micro mol/kg bodyweight; group II) were injected 2, 5 and 8 h later. A number of animals of both groups were killed 0, 12, 16, 24, 48 or 60 h after cadmium intoxication. Liver tissue was histologically assessed for necrosis, apoptosis, peliosis, mitoses, and inflammatory infiltration. Apoptosis was also quantified by the TUNEL assay for hepatocytes and nonparenchymal liver cells. The discrimination between hepatic cell subpopulations was achieved histochemically. The mitotic index in hematoxylin-eosin-stained sections and by the immunochemical detection of Ki67 nuclear antigen, (3)H-thymidine incorporation into hepatic DNA, and hepatic thymidine kinase activity were all used as indices of liver regeneration. Both hepatocyte apoptosis and liver necrosis evolved in a biphasic temporal pattern. Nonparenchymal cell apoptosis and peliosis hepatis evolved in a monophasic pattern and were correlated closely. Putrescine administration totally reversed liver necrosis and hepatocyte apoptosis. The time profile of nonparenchymal apoptosis was altered and peliosis hepatis was also totally attenuated. In conclusion, putrescine protected hepatocytes and modulated the mechanism of cadmium-induced acute hepatotoxicity.