Clarithromycin, trimethoprim, and penicillin and oxidative nucleic acid modifications in humans: randomised, controlled trials
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Clarithromycin, trimethoprim, and penicillin and oxidative nucleic acid modifications in humans : randomised, controlled trials. / Larsen, Emil List; Cejvanovic, Vanja; Kjær, Laura Kofoed; Pedersen, Morten Thorup; Popik, Sara Daugaard; Hansen, Lina Kallehave; Andersen, Jon Thor Trærup; Solem, Espen Victor Jimenez; Broedbaek, Kasper; Petersen, Morten; Weimann, Allan; Henriksen, Trine; Lykkesfeldt, Jens; Torp-Pedersen, Christian; Poulsen, Henrik Enghusen.
In: British Journal of Clinical Pharmacology, Vol. 83, No. 8, 08.2017, p. 1643-1653.Research output: Contribution to journal › Journal article › Research › peer-review
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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 - Kjær, Laura Kofoed
AU - Pedersen, Morten Thorup
AU - Popik, Sara Daugaard
AU - Hansen, Lina Kallehave
AU - Andersen, Jon Thor Trærup
AU - Solem, Espen Victor Jimenez
AU - Broedbaek, Kasper
AU - Petersen, Morten
AU - Weimann, Allan
AU - Henriksen, Trine
AU - Lykkesfeldt, Jens
AU - Torp-Pedersen, Christian
AU - Poulsen, Henrik Enghusen
PY - 2017/8
Y1 - 2017/8
N2 - AimsIn 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.MethodsThis study contains information from two randomised, controlled trials. Participants underwent 1 week treatment with clarithromycin, trimethoprim, phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-h urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde before and after treatment as a measurement of DNA oxidation, RNA oxidation, and lipid peroxidation, respectively.ResultsClarithromycin significantly increased urinary excretion of 8-oxodG by 22.0% (95% confidence interval (CI): 3.6–40.4%) and 8-oxoGuo by 14.9% (95% CI: 3.7–26.1%). 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 malondialdehyde.ConclusionClarithromycin 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 - AimsIn 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.MethodsThis study contains information from two randomised, controlled trials. Participants underwent 1 week treatment with clarithromycin, trimethoprim, phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-h urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde before and after treatment as a measurement of DNA oxidation, RNA oxidation, and lipid peroxidation, respectively.ResultsClarithromycin significantly increased urinary excretion of 8-oxodG by 22.0% (95% confidence interval (CI): 3.6–40.4%) and 8-oxoGuo by 14.9% (95% CI: 3.7–26.1%). 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 malondialdehyde.ConclusionClarithromycin 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.
KW - antibiotics
KW - oxidative stress
KW - 8-oxo-7
KW - 8-dihydro-2-deoxyguanosine
KW - 8-dihydroguanosine
KW - DNA oxidation
KW - RNA oxidation
U2 - 10.1111/bcp.13261
DO - 10.1111/bcp.13261
M3 - Journal article
C2 - 28185274
VL - 83
SP - 1643
EP - 1653
JO - British Journal of Clinical Pharmacology, Supplement
JF - British Journal of Clinical Pharmacology, Supplement
SN - 0264-3774
IS - 8
ER -
ID: 182122640