An ultrastructural and histochemical study of the prominent inflammatory response in D(+)-galactosamine hepatotoxicity

Abstract

The biochemical basis of the hepatitis-like liver injury produced by D(+)-galactosamine in rats is well-established and is linked to depletion of uridine nucleotides within parenchymal cells. However, the prominent inflammatory response that accompanies this lesion in vivo has been largely overlooked as a component of the hepatic damage. This study examines the cellular components of the inflammatory infiltrate of galactosamine-induced liver injury over time using histochemical and ultrastructural techniques. By 12 h after toxin administration, the infiltrate consisted largely of neutrophils and recently-mobilized monocytes. By 24 to 48 h after the toxin, when hepatocellular necrosis was maximal, few neutrophils were found in the infiltrate. At these times, the infiltrate consisted almost exclusively of large phagocytic cells, histochemically and morphologically consistent with active tissue macrophages apparently derived from circulating monocytes. The extent of the inflammatory response to this experimental hepatotoxin suggests that effects on the generation and development of the inflammatory response should be considered for treatments reported to alter the intrinsic hepatotoxicity of galactosamine.