LIVER PARENCHYMAL CELL INJURY

Abstract

Iodoform, a relatively water-insoluble yellow solid, chemically reactive in free-radical reactions, produces early hepatocellular injury qualitatively similar to that of carbon tetrachloride. 2 hr after administration of radioactively labeled iodoform, nonvolatile 14C is preferentially recovered in microsomal lipid and protein. By 30 min microsomal properties are profoundly affected: oxidative demethylation decreases abruptly; increased lipoperoxide decomposition products are detected; and amino acid incorporation into liver protein is depressed. By 1 hr glucose-6-phosphatase is suppressed centrolobularly and increased stainable calcium is present in the midzone. Increased cell sap RNA contents are observed by 2 hr. Morphologically, the biochemical and histochemical changes are associated with progressive dispersion, vacuolation, and degranulation of the granular endoplasmic reticulum. Calcium-associated masses accumulate within the mitochondrial matrix, and mitochondria become progressively pleomorphic. Golgi components dilate and disperse. Membranous components of the cytoplasm of parenchymal cells conglomerate into labyrinthine tubular aggregates. Lipid accumulates in cytoplasmic droplets. Ultimately, centrolobular necrosis ensues. The close cytochemical and morphological similarities between the cellular injury produced in the liver by iodoform and that produced by carbon tetrachloride suggest common pathogenetic mechanisms associated with damage to membranes.