Effect of colchicine on acetaminophen-induced liver damage.
The effect of colchicine on liver damage induced by acetaminophen (APAP) intoxication was studied. Wistar male rats pretreated (72 h) with 3-methylcholanthrene (3-MC) (20 mg/kg i.p.) were divided into six groups: animals in group 1 were treated with acetaminophen (APAP) (500 mg/kg p.o.); group 2 consisted of animals that received colchicine (65 micrograms/kg/day p.o.) for 7 days before APAP intoxication; group 3 was treated like group 2, but the dose of colchicine was 300 micrograms/kg/day; animals in groups 4 and 5 received the same doses of colchicine as groups 2 and 3, respectively, but received the vehicle instead of APAP; and rats in group 6 (control) received the equivalent amount of the vehicles. Animals were sacrificed at different times after APAP administration. Reduced glutathione (GSH), lipid peroxidation and glycogen were measured in liver and, gamma-glutamyl transpeptidase (gamma-GTP), and glutamic pyruvic transaminase (GPT) activities were measured in serum. After APAP intoxication, GSH and glycogen decreased very fast (1 h) and remained low for 6 h. Lipid peroxidation increased three times over control 4 h after APAP treatment. Enzyme activities increased at 18 h after intoxication. Pretreatment with 65 micrograms/kg of colchicine failed to prevent liver damage induced by APAP. However, when a dose of 300 micrograms/kg of colchicine was given, levels of lipid peroxidation and serum gamma-GTP activity remained within the control values, while GPT activity and glycogen content were only partially attenuated. It was concluded that colchicine protects against APAP intoxication, probably through its antioxidant properties, possibly acting as a free radical scavenger.
Departamento de Farmacologia y Toxicologia, Instituto Politecnico Nacional, Mexico.
P
P
Muriel
M E
ME
Quintanar
V
V
Perez-Alvarez
D000082:Acetaminophen / Q000506:poisoning*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D003078:Colchicine / Q000627:therapeutic use*; D016166:Free Radical Scavengers; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011292:Premedication; D051381:Rats; D017208:Rats, Wistar
D016166:Free Radical Scavengers; D000082:Acetaminophen; D003078:Colchicine