Mitochondrial Toxicity of Azithromycin Results in Aerobic Glycolysis and DNA Damage of Human Mammary Epithelia and Fibroblasts

Antibiotics
Xian-Peng JiangRobert L Elliott

Abstract

Mitochondria evolved from free-living bacteria via endocytosis within eukaryotic host cells millions of year ago. We hypothesized that antibiotics cause mammalian mitochondrial damage while causing bacterial lethality. Mitochondrial toxicity of azithromycin in human mammary epithelia MCF-12A and fibroblasts were tested by fluorescent and transmission electron microscopy. Gene expression and DNA damage were tested by real-time polymerase chain reaction (qPCR) and ELISA. We found azithromycin suppressed the mitochondrial membrane potential gradient of MCF-12A cells and fibroblasts. Ultrastructure exams showed that the antibiotic caused vacuolated and swollen mitochondria with disrupted cristae in MCF-12A cells and fibroblasts compared to the morphology of mitochondria in the cells without antibiotic treatment. Fluorescent microscopy also showed azithromycin-induced mitochondrial reactive oxygen species (ROS), superoxide, after 3 h of culture. The DNA oxidative damage product, 8-hydroxy-2'-deoxyguanosine (8-OHdG, significantly increased in the media after MCF-12A cells and fibroblasts were cultured in the media containing azithromycin for 24 h. Azithromycin upregulated gene expression of hypoxia inducible factor 1 alpha (HIF1a), g...Continue Reading

References

Sep 12, 1991·The American Journal of Medicine·S Hopkins
Oct 1, 1991·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·P J McDonald, H Pruul
Mar 5, 1999·Science·M W GrayB F Lang
Nov 17, 2001·International Journal of Antimicrobial Agents·W L Hand, D L Hand
Feb 19, 2004·JAMA : the Journal of the American Medical Association·Christine M VelicerStephen H Taplin
May 13, 2006·Journal of Carcinogenesis·Gulam Waris, Haseeb Ahsan
Jun 5, 2008·The Journal of Biological Chemistry·Stefan Dröse, Ulrich Brandt
Jul 25, 2008·Nature·Alberto MantovaniFrances Balkwill
Dec 9, 2008·The Biochemical Journal·Michael P Murphy
Jan 15, 2009·Nature Reviews. Cancer·Nicholas C Denko
Dec 29, 2009·Current Opinion in Genetics & Development·Sergei I Grivennikov, Michael Karin
Oct 12, 2010·Biochimica Et Biophysica Acta·Richard C Scarpulla
May 23, 2012·Antimicrobial Agents and Chemotherapy·Alison E BarnhillSteve A Carlson
Jun 7, 2012·Journal of the Neurological Sciences·Antonio FedericoElena Radi
Sep 7, 2012·Cold Spring Harbor Perspectives in Biology·Michael W Gray
Jan 30, 2013·Antimicrobial Agents and Chemotherapy·P MatznellerM Zeitlinger
Jul 5, 2013·Science Translational Medicine·Sameer KalghatgiJames J Collins
Dec 10, 2013·Free Radical Biology & Medicine·Rob van ZwietenDirk Roos
Feb 27, 2014·American Journal of Physiology. Endocrinology and Metabolism·Yogeshwar MakanjiTeresa K Woodruff
Jun 13, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Ahmad SalimiJalal Pourahmad
Dec 1, 2015·BioMed Research International·Bolan Yu, Zhaofeng Huang
Jan 4, 2017·Oncotarget·Míriam Tarrado-CastellarnauMarta Cascante
Jul 26, 2018·Molecular Cancer Research : MCR·Tsutomu ShimuraNaoki Kunugita
Aug 8, 2018·Therapeutic Advances in Ophthalmology·Kostas A KagkelarisGeorge D Panayiotakopoulos

❮ Previous
Next ❯

Methods Mentioned

BETA
transmission electron microscopy
Polymerase Chain Reaction
PCR
PCRs
Assay
ELISA

Software Mentioned

Cellsens
RQ Manager

Related Concepts