Cell death and barrier disruption by clinically used iodine concentrations.

Autor: Steins A; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Australian National University, Acton, Australia.; College of Health and Medicine, Australian National University, Acton, Australia., Carroll C; College of Health and Medicine, Australian National University, Acton, Australia., Choong FJ; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Australian National University, Acton, Australia., George AJ; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Australian National University, Acton, Australia.; ANU Centre for Therapeutic Discovery, Australian National University, Acton, Australia., He JS; Division of Immunology and Infectious Disease, The John Curtin School of Medical Research, Australian National University, Acton, Australia., Parsons KM; Division of Immunology and Infectious Disease, The John Curtin School of Medical Research, Australian National University, Acton, Australia., Feng S; Division of Immunology and Infectious Disease, The John Curtin School of Medical Research, Australian National University, Acton, Australia., Man SM; Division of Immunology and Infectious Disease, The John Curtin School of Medical Research, Australian National University, Acton, Australia., Kam C; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Australian National University, Acton, Australia., van Loon LM; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Australian National University, Acton, Australia.; College of Health and Medicine, Australian National University, Acton, Australia., Poh P; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Australian National University, Acton, Australia., Ferreira R; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Australian National University, Acton, Australia., Mann GJ; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Australian National University, Acton, Australia.; College of Health and Medicine, Australian National University, Acton, Australia., Gruen RL; College of Health and Medicine, Australian National University, Acton, Australia., Hannan KM; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Australian National University, Acton, Australia.; College of Health and Medicine, Australian National University, Acton, Australia., Hannan RD; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Australian National University, Acton, Australia.; College of Health and Medicine, Australian National University, Acton, Australia., Schulte KM; Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Australian National University, Acton, Australia km.schulte@anu.edu.au.; College of Health and Medicine, Australian National University, Acton, Australia.; Department of Endocrine Surgery, King's College Hospital NHS Foundation Trust, London, UK.
Jazyk: angličtina
Zdroj: Life science alliance [Life Sci Alliance] 2023 Mar 21; Vol. 6 (6). Date of Electronic Publication: 2023 Mar 21 (Print Publication: 2023).
DOI: 10.26508/lsa.202201875
Abstrakt: 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 (I 2 ), 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 I 2 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.
(© 2023 Steins et al.)
Databáze: MEDLINE
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