TY - JOUR T1 - Cell death and barrier disruption by clinically used iodine concentrations JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202201875 VL - 6 IS - 6 SP - e202201875 AU - Anne Steins AU - Christina Carroll AU - Fui Jiun Choong AU - Amee J George AU - Jin-Shu He AU - Kate M Parsons AU - Shouya Feng AU - Si Ming Man AU - Cathelijne Kam AU - Lex M van Loon AU - Perlita Poh AU - Rita Ferreira AU - Graham J Mann AU - Russell L Gruen AU - Katherine M Hannan AU - Ross D Hannan AU - Klaus-Martin Schulte Y1 - 2023/06/01 UR - https://www.life-science-alliance.org/content/6/6/e202201875.abstract N2 - 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. ER -