Colchicine prevents D-galactosamine-induced hepatitis.
The hepatoprotective effect of colchicine in a model of liver intoxication with galactosamine (GalN), 375 mg/kg, i.p., was studied in rats. At 0.5, 1, 3, 6, 18 and 24 h after GalN intoxication the following markers of liver damage were measured: serum activity of alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, hepatic calcium and glycogen contents, liver lipoperoxidation, and liver plasma membrane activity of alkaline phosphatase, gamma-glutamyltranspeptidase and high-affinity Ca2+-ATPase. 24 h after GalN intoxication increases in serum levels of alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase were observed along with decreases in plasma membrane activities of alkaline phosphatase, gamma-glutamyltranspeptidase, and high-affinity Ca2+-ATPase. A sharp increase of lipoperoxidative processes measured as malondialdehyde production was also observed. Pretreatment of rats with colchicine 10 micrograms/rat/day p.o. for 7 days before GalN injection prevented partially the toxic effects of GalN. When a dose of 50 micrograms/rat/day for 7 days was given the drug prevented almost completely the damage induced by galactosamine, with the exception of glycogen and serum alkaline phosphatase that remained different from controls. Time-course experiments showed that malondialdehyde formation increased 30 min after intoxication while all other changes became apparent from 6 h after treatment, suggesting that lipoperoxidation may be a prerequisite for galactosamine-induced damage. The protection offered by colchicine was related to its capacity to inhibit lipoperoxidation. Histochemical findings paralleled the biochemical results. The possible role of lipoperoxidation in galactosamine-induced liver damage is discussed.
Mourelle
M
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Pharmacology and Toxicology Department, CINVESTAV-IPN, Mexico City, Mexico.
Meza
M A
MA
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D003078:Colchicine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005688:Galactosamine / Q000037:antagonists & inhibitors*; D006003:Glycogen / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000097:blood
D005688:Galactosamine; D006003:Glycogen; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D000252:Calcium-Transporting ATPases; D003078:Colchicine; D002118:Calcium