TY - JOUR
T1 - Clarithromycin, trimethoprim, and penicillin and oxidative nucleic acid modifications in humans
T2 - randomised, controlled trials
AU - Larsen, Emil List
AU - Cejvanovic, Vanja
AU - Kjaer, Laura Kofoed
AU - Pedersen, Morten Thorup
AU - Popik, Sara Daugaard
AU - Hansen, Lina Kallehave
AU - Andersen, Jon Traerup
AU - Jimenez-Solem, Espen
AU - Broedbaek, Kasper
AU - Petersen, Morten
AU - Weimann, Allan
AU - Henriksen, Trine Brink
AU - Lykkesfeldt, Jens
AU - Torp-Pedersen, Christian
AU - Poulsen, Henrik Enghusen
N1 - This article is protected by copyright. All rights reserved.
PY - 2017
Y1 - 2017
N2 - AIMS: In vitro studies have demonstrated that formation of reactive oxygen species (ROS) contributes to the effect of bactericidal antibiotics. The formation of ROS is not restricted to bacteria, but also occurs in mammalian cells. Oxidative stress is linked to several diseases. This study investigates whether antibiotic drugs induce oxidative stress in healthy humans as a possible mechanism for adverse reactions to the antibiotic drugs.METHODS: This study contains information from two randomised, controlled trials. Participants underwent one-week treatment with clarithromycin, trimethoprim, phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-hour urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde (MDA) before and after treatment as a measurement of DNA oxidation, RNA oxidation, and lipid peroxidation, respectively.RESULTS: Clarithromycin significantly increased urinary excretion of 8-oxodG by 22.0 % (95% CI: 3.6-40.4 %) and 8-oxoGuo by 14.9 % (95% CI: 3.7-26.1 %), which could be a possible mechanism to some of its adverse reactions. Further, we demonstrated that trimethoprim significantly lowered urinary excretion of 8-oxodG by 21.7 % (95% CI: 5.8-37.6 %), but did not influence urinary excretion of 8-oxoGuo. Penicillin V did not influence urinary excretion of 8-oxodG or 8-oxoGuo. None of the antibiotic drugs influenced plasma levels of MDA.CONCLUSION: Clarithromycin significantly increases oxidative nucleic acid modifications. Increased oxidative modifications might explain some of clarithromycin's known adverse reactions. Trimethoprim significantly lowers DNA oxidation but not RNA oxidation. Penicillin V had no effect on oxidative nucleic acid modifications.
AB - AIMS: In vitro studies have demonstrated that formation of reactive oxygen species (ROS) contributes to the effect of bactericidal antibiotics. The formation of ROS is not restricted to bacteria, but also occurs in mammalian cells. Oxidative stress is linked to several diseases. This study investigates whether antibiotic drugs induce oxidative stress in healthy humans as a possible mechanism for adverse reactions to the antibiotic drugs.METHODS: This study contains information from two randomised, controlled trials. Participants underwent one-week treatment with clarithromycin, trimethoprim, phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-hour urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde (MDA) before and after treatment as a measurement of DNA oxidation, RNA oxidation, and lipid peroxidation, respectively.RESULTS: Clarithromycin significantly increased urinary excretion of 8-oxodG by 22.0 % (95% CI: 3.6-40.4 %) and 8-oxoGuo by 14.9 % (95% CI: 3.7-26.1 %), which could be a possible mechanism to some of its adverse reactions. Further, we demonstrated that trimethoprim significantly lowered urinary excretion of 8-oxodG by 21.7 % (95% CI: 5.8-37.6 %), but did not influence urinary excretion of 8-oxoGuo. Penicillin V did not influence urinary excretion of 8-oxodG or 8-oxoGuo. None of the antibiotic drugs influenced plasma levels of MDA.CONCLUSION: Clarithromycin significantly increases oxidative nucleic acid modifications. Increased oxidative modifications might explain some of clarithromycin's known adverse reactions. Trimethoprim significantly lowers DNA oxidation but not RNA oxidation. Penicillin V had no effect on oxidative nucleic acid modifications.
U2 - 10.1111/bcp.13261
DO - 10.1111/bcp.13261
M3 - Journal article
C2 - 28185274
SN - 0306-5251
VL - 83
SP - 1643
EP - 1653
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
IS - 8
ER -