Cytotoxicity of contact lens multipurpose solutions: role of oxidative stress, mitochondrial activity and P2X7 cell death receptor activation.
OBJECTIVE
To investigate the cytotoxicity of multipurpose solutions used for contact lens disinfection.


METHODS
Four multipurpose solutions (Optifree containing quaternary ammonium as preservative, Renu, Solocare and Complete containing polyhexamethylene biguanide as preservative) were incubated on a conjunctival cell line to evaluate their capacity to induce necrosis (neutral red test), intracellular redox status alteration (Alamar Blue test), reactive oxygen species overproduction (DCFH-DA and dihydroethidium tests), mitochondrial alterations (NonylAcridine Orange and JC-1 tests) and to activate P2X7 cell death receptor (YO-PRO-1 test). Tests were performed using cytofluorometry and inverted fluorescence microscopy.


RESULTS
Our results showed that multipurpose solutions induced necrosis, in addition to oxidative stress. Optifree induced oxidative stress with increased mitochondrial mass, Renu, Solocare and Complete induced whether a decrease in reactive oxygen species production with mitochondrial alterations, or an increase in reactive oxygen species production, but each solution stimulated P2X7 cell death receptor activation. Early stimulation of P2X7 cell death receptor, prior to any superoxide production, demonstrated the possible involvement of this receptor in the oxidative stress process.


CONCLUSIONS
These new findings suggest that most of multipurpose solutions are toxic with oxidative stress and apoptosis induction.
Dutot
Mélody
M
Laboratoire de Toxicologie, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Paris 75006, France.
Warnet
Jean-Michel
JM
Baudouin
Christophe
C
Rat
Patrice
P
D017209:Apoptosis / Q000187:drug effects*; D001645:Biguanides / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003228:Conjunctiva / Q000166:cytology; D018639:Contact Lens Solutions / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009336:Necrosis / Q000139:chemically induced; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D013481:Superoxides / Q000378:metabolism
D001645:Biguanides; D018639:Contact Lens Solutions; C546468:P2RX7 protein, human; C546470:P2rx7 protein, rat; D011310:Preservatives, Pharmaceutical; D000644:Quaternary Ammonium Compounds; D017382:Reactive Oxygen Species; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D013481:Superoxides; C031233:polihexanide; D006861:Hydrogen Peroxide