Cellular Injury Induced by Reactive Cefaclor Metabolites: Absence of Apoptosis as a Mechanism of Cell Death

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Differential cellular toxicity to reactive cefaclor metabolites appears to be a key element in the pathogenesis of cefaclor-induced serum sickness-like reactions (SSLR). Currently the mechanism(s) of cell death are unknown. Given the involvement of the immune system in SSLR, apoptosis may be involved in the pathogenesis of these reactions. Cefaclor reactive metabolites were generated by a horseradish peroxidase (HRP) system and incubated with peripheral blood mononuclear cells. The development of apoptosis was studied using: 1) DNA fragmentation and 2) the Apoalert Annexin V Apoptosis assay which detects the externalization of membrane phosphatidylserine on apoptotic cells. Dose-dependent toxicity was demonstrated by drug activation with the HRP system; significantly more cell death was seem among cells incubated with drug and activating system versus a drug alone control (3% ± 2% for control concentration of 62.5 mM versus 12.4 ± 5.5% at a concentration of 62.5 mM plus activating system, p<0.05). There was no evidence of apoptosis at 6, 12, 24 and 36 hours after incubation with drug and activating system. This data was consistent with both the DNA fragmentation and Apoalert assays. Thus, although the development of SSLR is clearly mediated at least in part by the immune system, apoptosis does not appear to be involved in the pathogenesis of cefaclor-induced SSLR.

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Tschen, A., Wijsman, J., Matsui, D. et al. Cellular Injury Induced by Reactive Cefaclor Metabolites: Absence of Apoptosis as a Mechanism of Cell Death. Pediatr Res 45, 71 (1999). https://doi.org/10.1203/00006450-199904020-00426

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