RT Journal Article
SR Electronic
T1 Cell death and barrier disruption by clinically used iodine concentrations
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201875
DO 10.26508/lsa.202201875
VO 6
IS 6
A1 Steins, Anne
A1 Carroll, Christina
A1 Choong, Fui Jiun
A1 George, Amee J
A1 He, Jin-Shu
A1 Parsons, Kate M
A1 Feng, Shouya
A1 Man, Si Ming
A1 Kam, Cathelijne
A1 van Loon, Lex M
A1 Poh, Perlita
A1 Ferreira, Rita
A1 Mann, Graham J
A1 Gruen, Russell L
A1 Hannan, Katherine M
A1 Hannan, Ross D
A1 Schulte, Klaus-Martin
YR 2023
UL http://www.life-science-alliance.org/content/6/6/e202201875.abstract
AB Povidone-iodine (PVP-I) inactivates a broad range of pathogens. Despite its widespread use over decades, the safety of PVP-I remains controversial. Its extended use in the current SARS-CoV-2 virus pandemic urges the need to clarify safety features of PVP-I on a cellular level. Our investigation in epithelial, mesothelial, endothelial, and innate immune cells revealed that the toxicity of PVP-I is caused by diatomic iodine (I2), which is rapidly released from PVP-I to fuel organic halogenation with fast first-order kinetics. Eukaryotic toxicity manifests at below clinically used concentrations with a threshold of 0.1% PVP-I (wt/vol), equalling 1 mM of total available I2. Above this threshold, membrane disruption, loss of mitochondrial membrane potential, and abolition of oxidative phosphorylation induce a rapid form of cell death we propose to term iodoptosis. Furthermore, PVP-I attacks lipid rafts, leading to the failure of tight junctions and thereby compromising the barrier functions of surface-lining cells. Thus, the therapeutic window of PVP-I is considerably narrower than commonly believed. Our findings urge the reappraisal of PVP-I in clinical practice to avert unwarranted toxicity whilst safeguarding its benefits.