Cell death and barrier disruption by clinically used iodine concentrations

Area of Science:

• Cellular biology
• Toxicology
• Antimicrobial agents

Background:

• Povidone-iodine (PVP-I) is a widely used antiseptic with a broad spectrum of antimicrobial activity.
• Despite its long history of use, concerns regarding the safety of PVP-I persist, particularly during the SARS-CoV-2 pandemic.
• Clarifying the cellular mechanisms of PVP-I toxicity is crucial for its safe application.

Purpose of the Study:

• To investigate the cellular toxicity of Povidone-iodine (PVP-I) at a molecular and cellular level.
• To identify the specific component of PVP-I responsible for its toxicity.
• To characterize the cellular consequences and define the toxicity threshold of PVP-I.

Main Methods:

• In vitro studies using epithelial, mesothelial, endothelial, and innate immune cells.
• Kinetic analysis of diatomic iodine (I2) release from PVP-I.
• Assessment of cell viability, mitochondrial membrane potential, and oxidative phosphorylation.
• Evaluation of effects on cell membrane integrity and tight junctions.

Main Results:

• PVP-I toxicity is attributed to diatomic iodine (I2) released with first-order kinetics.
• Cellular toxicity is observed at concentrations below 0.1% PVP-I (1 mM I2).
• Above the toxicity threshold, PVP-I induces rapid cell death (iodoptosis) via membrane disruption and mitochondrial dysfunction, and compromises barrier function by affecting tight junctions.

Conclusions:

• The therapeutic window for PVP-I is narrower than previously assumed.
• Diatomic iodine (I2) is the primary toxic agent in PVP-I formulations.
• Clinical use of PVP-I warrants reappraisal to mitigate potential toxicity while preserving its antimicrobial benefits.