Ulrich R G, Petrella D K, Larsen E R, Cox J W, Cramer C T, Piper R C, Gray J E
Department of Pathology, Upjohn Company, Kalamazoo, Michigan 49001.
Fundam Appl Toxicol. 1990 Jan;14(1):60-70. doi: 10.1016/0272-0590(90)90231-8.
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.
本文所述研究旨在表征肝脏对一种新型氨基环醇抗生素硫酸妥布霉素的反应，该抗生素通过静脉注射（比格犬）或皮下注射（斯普拉格 - 道利大鼠）给予不同剂量水平，以研究观察到的变化的可逆性，并记录硫酸妥布霉素亚慢性给药的任何不良影响。在较高剂量组中，两个物种的血清丙氨酸和天冬氨酸转氨酶水平均显著升高。仅在犬中，较高剂量组还观察到短暂的神经肌肉阻滞。未观察到其他功能、形态或血清化学变化。通过电子显微镜检查肝脏发现存在细胞质层状包涵体，集中在肝细胞的胆小管区域。发现层状体的出现和转氨酶同时升高在停止治疗后是可逆的（在犬中研究）。大鼠酸性磷酸酶细胞化学的电子显微镜检查表明，大多数但并非所有层状体都含有这种酶。这一观察结果表明它们可能源自溶酶体，或者一旦形成就变成溶酶体。
