Gadolinium chloride pretreatment ameliorates acute cadmium-induced hepatotoxicity.

Cadmium is a known industrial and environmental pollutant. It causes hepatotoxicity upon acute administration. Features of cadmium-induced acute hepatoxicity encompass necrosis, apoptosis, peliosis and inflammatory infiltration. Gadolinium chloride (GdCl3) may prevent cadmium-induced hepatotoxicity by suppressing Kupffer cells. The effect of GdCl3 pretreatment on a model of acute cadmium-induced liver injury was investigated. Male Wistar rats 4-5 months old were injected intraperitoneally with normal saline followed by cadmium chloride (CdCl2; 6.5 mg/kg) or GdCl3 (10 mg/kg) followed by CdCl2 (6.5 mg/kg; groups I and II, respectively). Rats of both the groups were killed at 9, 12, 16, 24, 48 and 60 h after cadmium intoxication. Liver sections were analyzed for necrosis, apoptosis, peliosis and mitoses. Liver regeneration was also evaluated by tritiated thymidine incorporation into hepatic DNA. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also determined. Hepatic necrosis, hepatocyte and nonparenchymal cell apoptosis and macroscopic and microscopic types of peliosis hepatis were minimized by gadolinium pretreatment. Serum levels of AST and ALT were also greatly diminished in rats of group II. Tritiated thymidine incorporation into hepatic DNA was increased in gadolinium pretreatment rats. Kupffer cell activation was minimal in both the groups of rats. Gadolinium pretreatment attenuates acute cadmium-induced liver injury in young Wistar rats, with mechanisms other than Kupffer cell elimination.

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.