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 CCl(4)-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 CCl(4), CCl(4)+GdCl(3), GdCl(3), and vehicles. CCl(4) was given orally (0.4 g 100 g(-1) body wt.) and GdCl(3) (0.20 g 100 g(-1) body wt.) was administered i.p. All the animals were killed 24 h after treatment with CCl(4) 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. CCl(4) induced significant elevations on enzyme activities and bilirubins; GdCl(3) completely prevented this effect. Liver lipid peroxidation increased 2.5-fold by CCl(4) treatment; this effect was also prevented by GdCl(3). Glycogen stores were depleted by acute intoxication with CCl(4). However, GdCl(3) 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 GdCl(3) prevented both lipid peroxidation and CCl(4)-induced liver injury.
Muriel
P
P
Sección Externa de Farmacología, CINVESTAV-I.P.N. Apdo. Postal 14-740, 07000, D.F., México, Mexico. pmuriel@mail.cinvestav.mx
Alba
N
N
Pérez-Alvarez
V M
VM
Shibayama
M
M
Tsutsumi
V K
VK
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001663:Bilirubin / Q000819:agonists / Q000097:blood; D002251:Carbon Tetrachloride; D002462:Cell Membrane / Q000201:enzymology; D005682:Gadolinium / Q000494:pharmacology*; D006003:Glycogen / Q000037:antagonists & inhibitors*; D007728:Kupffer Cells / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D017093:Liver Failure / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D005723:gamma-Glutamyltransferase / Q000097:blood / Q000187:drug effects
D006003:Glycogen; D005682:Gadolinium; D002251:Carbon Tetrachloride; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; C038958:gadolinium chloride; D001663:Bilirubin