Colchicine prevents d-galactosamine-induced hepatitis

Abstract

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, γ-glutamyltranspeptidase, hepatic calcium and glycogen contents, liver lipoperoxidation, and liver plasma membrane activity of alkaline phosphatase, γ-glutamyltranspeptidase and high-affinity Ca 2+-ATPase. 24 h after GalN intoxication increases in serum levels of alanine aminotransferase, alkaline phosphatase and γ-glutamyltranspeptidase were observed along with decreases in plasma membrane activities of alkaline phosphatase, γ-glutamyltranspeptidase, and high-affinity Ca 2+-ATPase. A sharp increase of lipoperoxidative processes measured as malondialdehyde production was also observed. Pretreatment of rats with colchicine 10 μg/rat/day p.o. for 7 days before GalN injection prevented partially the toxic effects of GalN. When a dose of 50μg/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 ihat 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.