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© 1990 Oxford University Press

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Hepatic Changes Produced by 30-Day Administration of a Novel Aminocyclitol Antibiotic, Trospectomycin Sulfate, to Laboratory Animals

ROGER G. ULRICH, DIANE K. PETRELLA, ERIK R. LARSEN, JEFFREY W. COX*, CLAY T. CRAMER, RICHARD C. PIPER and JACK E. GRAY

Departments of Pathology and Toxicology Research Kalamazoo, Michigan 49001 *Drug Metabolism Research, The Upjohn Company Kalamazoo, Michigan 49001

Received January 16, 1989; accepted June 15, 1989

Hepatic Changes Produced by 30-Day Administration of a Novel Aminocyclitol Antibiotic, Trospectomycin Sulfate, to Laboratory Animals. ULRICH, R. G., PETRELLA, D. K., LARSEN, E. R., COX, J. W., CRAMER, C. T., PIPER, R. C, AND GRAY, J. E. (1990). Fundam. Appl. Toxi-col. 14, 60–70. The studies described here were done to characterize the hepatic response to a new aminocyclitol antibiotic, trospectomycin sulfate, administered intravenously (beagle dog) or subcutaneously (Sprague-Dawley rat) at a variety of dose levels, to investigate reversibility of observed changes, and to document any untoward effects of subchronic trospectomycin sulfate administration. Both species showed significant elevations in serum levels of alanine and aspartate transaminases in higher dose groups. In the dog only, a transient neuromuscular blockade was also observed within higher dose groups. No other functional, morphological, or serum chemical changes were observed. Examination of liver by electron microscopy revealed the presence of cytoplasmic lamellar inclusion bodies, concentrated in the bile canalicular region of the hepatocytes. Occurrence of the lamellar bodies and coincident transaminase increases were found to be reversible upon discontinuance of treatment (studied in the dog). Electron microscopy of acid phosphatase cytochemistry in the rat indicated that most, but not all, of the lamellar bodies contained this enzyme. This observation suggests that they may be derived from the lysosome, or once formed become lysosomal.


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