title: Gadolinium chloride pretreatment ameliorates acute cadmium-induced hepatotoxicity.
abstract: 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.
authors.affiliation: Department of Experimental Pharmacology, Medical School, Athens University, Athens, Greece.
authors.forename: Loukas G
authors.initials: LG
authors.lastname: Kyriakou
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Tzirogiannis
authors.forename: Maria D
authors.initials: MD
authors.lastname: Demonakou
authors.forename: Kalliopi T
authors.initials: KT
authors.lastname: Kourentzi
authors.forename: Michael G
authors.initials: MG
authors.lastname: Mykoniatis
authors.forename: Georgios I
authors.initials: GI
authors.lastname: Panoutsopoulos
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D002104:Cadmium / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D005682:Gadolinium / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D009336:Necrosis / Q000139:chemically induced; D010382:Peliosis Hepatis / Q000139:chemically induced / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020011:Protective Agents; D002104:Cadmium; D005682:Gadolinium; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C038958:gadolinium chloride