375 Gene expression analysis of galactosamine-induced hepatotoxicity in-vivo and in-vitro

Abstract

Plasma hyaluronan (HA) concentration and the rate of HA uptake by the isolated, perfused liver were measured in rats treated with saline, D-galactosamine (GaINH2, 50 mg/100 g body wt), gadolinium chloride (GdCl3) (0.5 mg/100 g body wt), and GdCl3 + GaINH2. GdCl3 was given 24 hr before GaINH2 or saline. Plasma L-alanine:2-oxoglutarate aminotransferase (EC 2.6.1.2), a marker for hepatocyte damage, was increased by 8 hr and remained elevated for 24 hr after GaINH2 injection. GdCl3 did not affect plasma enzyme levels when given alone or in association with, but prior to, GaINH2. Plasma HA levels were increased (200%) within 2 hr GaI administration. A plateau was reached at 8 hr, which was maintained for at least 24 hr. Although GdCl3 alone did not affect plasma HA levels, it slightly delayed the increase in HA concentration in GaINH2-treated rats. Liver, isolated 24 hr after GaINH2 treatment, exhibited a severe depression (approximately 67%) of HA uptake. GdCL3 did not prevent this suppression. The data presented indicate that: (1) one of the sinusoidal endothelial cell-dependent functions of the liver, i.e. removal of HA from the blood stream, is profoundly impaired during galactosamine-induced hepatitis, and (2) the adverse effect of GaINH2 on this sinusoidal endothelial cell function may not be dependent on GdCl3-suppressible Kupffer cell functions.