Yunis A A
Department of Medicine, University of Miami School of Medicine, Florida 33101.
Am J Med. 1989 Sep;87(3N):44N-48N.
Significant progress has been made in recent years in the understanding of the pathogenesis of the two types of hematologic toxicity from chloramphenicol. The common, dose-dependent, reversible bone marrow suppression from chloramphenicol is a consequence of mitochondrial injury. The greater erythroid susceptibility to chloramphenicol appears to be a function of the endogenous mitochondrial amino acid pools. The pathogenesis of aplastic anemia from chloramphenicol treatment remains uncertain. A large body of indirect evidence favors a complex mechanism involving metabolic transformation of the p-NO2 group of chloramphenicol by the predisposed subject, leading to the production of a toxic intermediate causing stem cell damage. A concept is presented wherein metabolites of chloramphenicol generated by intestinal bacteria undergo further metabolic transformation in the bone marrow with in situ production of toxic intermediate. This concept of the marrow being both the metabolic site for the offending agent as well as the target for its toxic metabolites will likely apply to other potential myelotoxins.
近年来，在理解氯霉素引起的两种血液学毒性的发病机制方面取得了重大进展。氯霉素常见的、剂量依赖性的、可逆性骨髓抑制是线粒体损伤的结果。红细胞对氯霉素的易感性较高似乎是内源性线粒体氨基酸池的作用。氯霉素治疗引起再生障碍性贫血的发病机制仍不确定。大量间接证据支持一种复杂机制，即易感个体对氯霉素的对硝基（p-NO2）基团进行代谢转化，导致产生有毒中间体，从而造成干细胞损伤。本文提出了一个概念，即肠道细菌产生的氯霉素代谢产物在骨髓中进一步代谢转化，同时原位产生有毒中间体。骨髓既是致病因子的代谢场所，又是其有毒代谢产物的靶器官，这一概念可能适用于其他潜在的骨髓毒素。
