Faculty Bibliography

Troleandomycin, a macrolide antibiotic, has been shown to be demethylated and oxidized into a metabolite which forms an inactive complex with the iron(II) of cytochrome P-450. The role of glutathione in the metabolism of troleandomycin was investigated. Administration of troleandomycin (1 mmol X kg-1 p.o.) decreased the concentration of glutathione in the liver. The depletion of glutathione was increased in rats pretreated with phenobarbital and decreased in rats pretreated with CoCl2. In vitro, an inverse relationship was found between the concentration of glutathione in the incubation mixture and the appearance of the cytochrome P-450-troleandomycin metabolite complex. Glutathione, however, did not inhibit the demethylation of troleandomycin and did not destroy the cytochrome P-450-troleandomycin metabolite complex. The in vitro protective effect of glutathione was reproduced by cysteine but not by glycine. In vivo, decreasing the concentration of glutathione in the liver by food deprivation or by the administration of diethylmaleate increased the formation of the cytochrome P-450-troleandomycin metabolite complex. These results indicate that glutathione is depleted by a troleandomycin metabolite in vivo, whereas glutathione protects against the formation of the inactive cytochrome P-450-troleandomycin metabolite complex in vitro and in vivo

Liver histology was normal 24 h after the administration of trichloroethylene (1 ml . kg-1) in rats. It was normal, or showed necrosis of a few hepatocytes, after the administration of carbon tetrachloride (64 microliters . kg-1). In rats receiving both solvents, there was extensive centrilobular necrosis. In vitro, trichloroethylene did not initiate lipid peroxidation but potentiated that initiated by carbon tetrachloride; a similar potentiating effect was observed for a wide range of trichloroethylene concentrations (0.19-12 mM). In vivo, a wide range of trichloroethylene doses (0.064-1 ml . kg-1) similarly potentiated the hepatotoxicity of carbon tetrachloride. Administration of trichloroethylene (1 ml . kg-1), 5 h earlier, increased carbon tetrachloride-induced lipid peroxidation in vitro, and increased the hepatotoxicity of a subsequent dose of carbon tetrachloride (64 microliters . kg-1). Previous administration of carbon tetrachloride failed to modify lipid peroxidation and to increase the hepatotoxicity of trichloroethylene. We conclude that trichloroethylene potentiates the hepatotoxicity of carbon tetrachloride, possibly by increasing carbon tetrachloride-induced lipid peroxidation

The Hermansky-Pudlak syndrome consists of tyrosine-positive albinism, a defect in the second phase of platelet aggregation, and widespread accumulation of a ceroidlike pigment in tissue. Pulmonary fibrosis has also been reported. In this paper, we describe two families with documented Hermansky-Pudlak syndrome in which four members, two from each family, developed granulomatous colitis. This adds another disease entity to those associated with this syndrome. We discuss possible connecting links between these disease expressions