Holt D, Harvey D, Hurley R
Karim Centre for Meningitis Research, RPMS Institute of Obstetrics and Gynaecology, Queen Charlotte's and Chelsea Hospital, London, UK.
Adverse Drug React Toxicol Rev. 1993 Summer;12(2):83-95.
Although high serum concentrations of chloramphenicol are related to toxicity, as shown experimentally and during treatment, the mechanism of toxicity remains unclear. Published work suggests that relatively minor metabolites may be causally related to toxic reactions in vitro and some of these metabolites have been detected in sera from treated patients. It is possible that all the major toxic manifestations of chloramphenicol may be explained by attack by free radicals. Depletion in compounds acting as cellular antioxidants, such as glutathione and vitamin E, may conceivably increase the vulnerability of an individual to chloramphenicol toxicity, while supplementation with an antioxidant might protect against it. Research into the metabolism of chloramphenicol and into the mechanism of its toxicity has declined since early work in the 1950s and 1960s, but its continuing use worldwide means that there is justification for renewed interest in the toxicology of this useful antibiotic.
尽管如实验及治疗过程中所示,血清中氯霉素浓度过高与毒性相关,但其毒性机制仍不清楚。已发表的研究表明,相对次要的代谢产物可能在体外与毒性反应存在因果关系,并且在接受治疗患者的血清中已检测到其中一些代谢产物。氯霉素的所有主要毒性表现都有可能是由自由基攻击所致。诸如谷胱甘肽和维生素E等作为细胞抗氧化剂的化合物的消耗,可能会增加个体对氯霉素毒性的易感性,而补充抗氧化剂或许可以起到预防作用。自20世纪50年代和60年代的早期研究以来,对氯霉素代谢及其毒性机制的研究有所减少,但由于其在全球范围内仍在持续使用,因此有理由重新关注这种有用抗生素的毒理学。