Kupffer cells inhibition prevents hepatic lipid peroxidation and damage induced by carbon tetrachloride

The aim of this work was to determine if the action mechanism of gadolinium on CCl4-induced liver damage is by preventing lipid peroxidation (that may be induced by Kupffer cells) and its effects on liver carbohydrate metabolism. Four groups of rats were treated with CCl4, CCl4 + GdCl3, GdCl3, and vehicles. CCl4 was given orally (0.4 g 100 g(-1) body wt.) and GdCl3 (0.20 g 100 g(-1) body wt.) was administered i.p. All the animals were killed 24 h after treatment With CCl4 or vehicle. Glycogen and lipid peroxidation were measured in liver. Alkaline phosphatase, gamma -glutamyl transpeptidase, alanine amino transferase activities and bilirubins were measured in rat serum. A liver histological analysis was performed. CO, induced significant elevations on enzyme activities and bilirubins; GdCl3 completely prevented this effect. Liver lipid peroxidation increased 2.5-fold by CCl4 treatment; this effect was also prevented by GdCl3. Glycogen stores were depleted by acute intoxication with CCl4. However, GdCl3 did not prevent this effect. The present study shows that Kupffer cells may be responsible for liver damage induced by carbon tetrachloride and that lipid peroxidation is produced or stimulated by Kupffer cells, since their inhibition with GdCl3 prevented both lipid peroxidation and CCl4-induced liver injury. (C) 2001 Elsevier Science Inc. All rights reserved.