EFFECT OF COLCHICINE ON ACETAMINOPHEN-INDUCED LIVER-DAMAGE

The effect of colchicine on liver damage induced by acetaminophen (APA P) intoxication was studied. Wistar male rats pretreated (72 h) with 3 -methylcholantrene (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 mug/ kg/day p.o.) for 7 days before APAP intoxication; group 3 was treated like group 2, but the dose of colchicine was 300 mug/kg/day; animals i n 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 i n group 6 (control) received the equivalent amount of the vehicles. An imals were sacrificed at different times after APAP administration. Re duced 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 A PAP intoxication, GSH and glycogen decreased very fast (1 h) and remai ned low for 6 h. Lipid peroxidation increased three times over control 4 h after APAP treatment. Enzyme activities increased at 18 h after i ntoxication. Pretreatment with 65 mug/kg of colchicine failed to preve nt liver damage induced by APAP. However, when a dose of 300 mug/kg of colchicine was given, levels of lipid peroxidation and serum gamma-GT P 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 a ntioxidant properties, possibly acting as a free radical scavenger.