Abstract
In a recent human study, we observed that amoxicillin treatment decreased HDL-C concentration. We hypothesize that antibiotics lower the transcription and secretion of ApoA-I, the responsible protein for HDL production. HepG2 and Caco-2 cells were exposed to increasing dose of amoxicillin, penicillin, and streptomycin. Secreted ApoA-I protein and mRNA transcripts were analyzed using ELISA and qPCR, respectively. To unravel underlying mechanisms, KEAP1, CPT1, and CHOP mRNA expressions were determined as well as PPARα transactivation. In HepG2 and Caco-2, amoxicillin decreased ApoA-I transcription and secretion. Effects on ApoA-I expression were clearly there for amoxicillin while no effects were observed for penicillin or streptomycin. KEAP1, CPT1, and CHOP mRNA expressions were reduced by amoxicillin treatments. Moreover, a significant correlation between ApoA-I and CPT1 mRNA expressions was found. Furthermore, amoxicillin lowered PPARα transactivation. All together, these data suggest that inhibited PPARα transactivation is involved in the effects of amoxicillin on ApoA-I. In conclusion, the direct effect of amoxicillin in treated HepG2 and Caco-2 cells was a lower ApoA-I secretion and transcription. Based on evaluating alterations in KEAP1, CPT1, and CHOP mRNA expressions plus PPARα transactivation, we suggest that a reduced PPARα activation is a potential mechanism behind the observed amoxicillin effects on ApoA-I expression.
Highlights
Used antibiotics such as amoxicillin, penicillin, and streptomycin have been classified as essential drugs to treat many types of bacterial infections [1,2]
We focused on amoxicillin and penicillin, which both belong to the beta-lactams, and on streptomycin, which belongs to the aminoglycosides class
Regarding cardiovascular disease (CVD), we show here that one of these frequently used antibiotics, amoxicillin, had in vitro a direct negative effect on ApoA-I transcription and secretion by enterocytes and hepatocytes
Summary
Used antibiotics such as amoxicillin, penicillin, and streptomycin have been classified as essential drugs to treat many types of bacterial infections [1,2]. Besides treatment of bacterial infections, antibiotics influence the quantity and composition of the natural microbiota, which may be involved in a wide variety of physiological processes [3]. The question is whether antibiotics might affect CVD biomarkers, independent of effects on microbiota composition. The clinical relevance of this reduction as related to CVD is questionable since HDL functionality seems more important than HDL cholesterol concentrations [9]. HDL functionality has been attributed to its main structural protein, ApolipoproteinA-I (ApoA-I), which amongst other effects mediates the process of cholesterol efflux. We hypothesized that the reduction in serum HDL cholesterol concentrations as observed after amoxicillin treatment is related to a reduced ApoA-I transcription. We examined here the effects of different antibiotics, including amoxicillin, on ApoA-I transcription and secretion in hepatocytes and enterocytes. To understand the underlying mechanism, we addressed the potential involvement of BET inhibition [12], PPARα transactivation [13,14], or ER stress [15] on the antibiotic-induced changes in ApoA-I transcription
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
