To elucidate the mechanism by which dietary amino acids suppress the D-galactosamine (D-GalN)-induced hepatitis, we examined the involvement of Kupffer cells, tumor necrosis factor-alpha (TNF-alpha) and apoptosis in the mechanism. In experiment 1, the rats were fed with 10% L-glutamine or 5% glycine diet injected with D-GalN with or without gadolinium chloride (GdCl3)-pretreatment. The results indicated that these amino acids suppressed the D-GalN-induced elevation of serum transaminase activities, irrespective of GdCl3-pretreatment. In experiment 2, rats were fed with 10% of L-glutamine, L-serine, L-alanine or L-glutamic acid diets injected with D-GalN. The results demonstrated that all these amino acids suppressed the D-GalN-induced elevation of serum transaminase activities, but that serum TNF-alpha concentrations and hepatic caspase-3 activities in the rats were not appreciably changed. In conclusion, the suppressive effects of amino acids on D-GalN-induced hepatitis were suggested not to be always mediated by the inhibition of Kupffer cells --> TNF-alpha --> apoptosis pathway.
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