title: Polyoxyethylene hydrogenated castor oil modulates benzalkonium chloride toxicity: comparison of acute corneal barrier dysfunction induced by travoprost Z and travoprost.
abstract: OBJECTIVE
  To determine the element that modulates benzalkonium chloride (BAC) toxicity by using a new electrophysiological method to evaluate acute corneal barrier dysfunction induced by travoprost Z with sofZia (Travatan Z(®)), travoprost with 0.015% BAC (Travatan(®)), and its additives.
  
  
  METHODS
  Corneal transepithelial electrical resistance (TER) was measured in live white Japanese rabbits by 2 Ag/AgCl electrodes placed in the anterior aqueous chamber and on the cornea. We evaluated corneal TER changes after a 60-s exposure to travoprost Z, travoprost, and 0.015% BAC. Similarly, TER changes were evaluated after corneas were exposed for 60 s to the travoprost additives ethylenediaminetetraacetic acid disodium salt, boric acid, mannitol, trometamol, and polyoxyethylene hydrogenated castor oil 40 (HCO-40) with or without BAC. Corneal damage was examined after exposure to BAC with or without travoprost additives using scanning electron microscopy (SEM) and a cytotoxicity assay.
  
  
  RESULTS
  Although no decreases of TER were noted after exposure to travoprost Z with sofZia and travoprost with 0.015% BAC, a significant decrease of corneal TER was observed after 0.015% BAC exposure. With the exception of BAC, no corneal TER decreases were observed for any travoprost additives. After corneal exposure to travoprost additives with BAC, HCO-40 was able to prevent the BAC-induced TER decrease. SEM observations and the cytotoxicity assay confirmed that there was a remarkable improvement of BAC-induced corneal epithelial toxicity after addition of HCO-40 to the BAC.
  
  
  CONCLUSIONS
  Travoprost Z with sofZia and travoprost with BAC do not induce acute corneal barrier dysfunction. HCO-40 provides protection against BAC-induced corneal toxicity.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. uematsu-ngs@umin.ac.jp
authors.forename: Masafumi
authors.initials: M
authors.lastname: Uematsu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kumagami
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Shimoda
authors.forename: Mao
authors.initials: M
authors.lastname: Kusano
authors.forename: Mugen
authors.initials: M
authors.lastname: Teshima
authors.forename: Hideto
authors.initials: H
authors.lastname: To
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitaoka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D001548:Benzalkonium Compounds / Q000633:toxicity*; D002368:Castor Oil / Q000031:analogs & derivatives* / Q000494:pharmacology; D003008:Cloprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D017097:Electric Impedance; D004594:Electrophysiology; D005079:Excipients / Q000633:toxicity; D008297:Male; D008855:Microscopy, Electron, Scanning; D011310:Preservatives, Pharmaceutical / Q000633:toxicity; D011817:Rabbits; D000069557:Travoprost
chemical_list: D001548:Benzalkonium Compounds; D005079:Excipients; D011310:Preservatives, Pharmaceutical; D003008:Cloprostenol; C023040:polyethoxylated castor oil; D002368:Castor Oil; D000069557:Travoprost