Corneal epithelial cellular dysfunction from benzalkonium chloride (BAC) <i>in vitro</i>

Cha，Seung-Heon,; Lee, Jong-Soo; Oum, Boo Sup; Kim, Chi-Dae

doi:10.1111/j.1442-9071.2004.00782.x

Cited by 151 publications

(101 citation statements)

References 10 publications

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“…Its cytotoxic effect to corneal and conjunctival cells had been established in earlier studies. 30,31 To further support our studies, we used HCECs cultured in different concentrations of BAC to compare HCECs in FQ and in gentamicin solutions. In the first 30 min, the commercial ciprofloxacin and gentamicin solutions showed greater cytotoxicity than 0.005% BAC alone.…”

Section: Discussionmentioning

confidence: 99%

Comparison of fluoroquinolones: cytotoxicity on human corneal epithelial cells

Tsai

Chen

2009

Eye

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Purpose To compare the cytotoxicity of different fluoroquinolones (FQs) towards human corneal epithelial cells (HCECs). Methods HCECs were incubated with FQs (norfloxacin, ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, and gatifloxacin), both as commercial ophthalmic formulations and as unpreserved solutions. Cells incubated in different formulations of gentamicin, cefazolin, and benzalkonium chloride (BAC) were also compared. A cell viability assay, using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, was used to evaluate the drug effects on cell viability after five incubation times (30 min, 1 h, 4 h, 8 h, and 24 h). Transepithelial electrical resistance (TEER) was measured with a voltohmmeter to help understand changes in paracellular permeability at five time points (4 h, 8 h, 12 h, 24 h, and 48 h). Cell morphology was observed with an inverted fluorescence microscope, with multiple stage position and in time-lapse mode. Results The preserving solutions and BAC at concentrations above 0.005% significantly decreased cell viability, when assayed by MTS. Increased paracellular permeability and decreased membrane integrity were also observed by TEER measurements and inverted fluorescence microscopy. Ofloxacin and levofloxacin were both free of preservatives and showed the least cytotoxicity towards HCECs in commercial FQ eye drops. Conclusions The cytotoxicity observed with FQ eye drops seems to be caused mainly by the preservative, which induced a significant decrease in membrane integrity and increased paracellular permeability. We found the new generation of FQs (moxifloxacin and gatifloxacin) no less cytotoxic towards HCECs than the old generation ones.

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Section: Discussionmentioning

confidence: 99%

Comparison of fluoroquinolones: cytotoxicity on human corneal epithelial cells

Tsai

Chen

2009

Eye

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“…Benzalkonium chloride (BAK) is one of the most potent preservatives and a component of most eye drops, (Kaur et al 2009) because of its strong beneficial effect on microbacterial protection and solvent. On the other hand, BAK induces cytotoxic effects on cultured keratoconjunctival epithelial cells (Burstein 1980;De Saint Jean et al 2000;Cha et al 2004;Guenoun et al 2005;Leung et al 2008). The introduction of BAKcontaining eye drops was associated Effects of SofZia-preserved travoprost and benzalkonium chloride-preserved latanoprost on the ocular surface -a multicentre randomized single-masked study…”

Section: Introductionmentioning

confidence: 99%

Effects of SofZia‐preserved travoprost and benzalkonium chloride‐preserved latanoprost on the ocular surface – a multicentre randomized single‐masked study

Aihara

Oshima

Araie

2012

Acta Ophthalmologica

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ABSTRACT.Purpose: To assess the effect of SofZia-preserved travoprost on ocular surface conditions in comparison with benzalkonium chloride (BAK)-preserved latanoprost. Methods: A prospective randomized multicentre single-masked comparative study. Patients with open-angle glaucoma or ocular hypertension who had been treated with BAK-preserved latanoprost 0.005% (Xalatan Ò ) monotherapy for at least 3 months. Patients were enrolled at 23 facilities. Patients were randomly divided into the X-X group, continuous use of Xalatan Ò , or the X-T group, switching from Xalatan Ò to SofZia-preserved travoprost 0.004% (TravatanZ Ò ), and followed for 3 months. The superficial punctate keratopathy (SPK), conjunctival epitheliopathy, hyperaemia, tear break-up time (TBUT) and intraocular pressure (IOP) were examined for each patient in a masked manner. Changes in the frequency of keratoconjunctival epitheliopathy were evaluated 3 months after study initiation. Intra-and intergroup comparisons of changes in SPK, conjunctival epitheliopathy, hyperaemia, TBUT and IOP were also carried out. Results: Two hundred twenty patients participated and 215 completed the 3-month study. The frequency of keratoconjunctival epitheliopathy significantly decreased in the X-T group (p = 0.036) and the intergroup difference was also significant (p = 0.001). SPK scores and TBUT were significantly improved in the X-T group (p = 0.034, 0.049), also with significant intergroup differences in the cornea excluding the inferior area and TBUT. There were no significant intergroup differences in changes of the hyperaemia scores and the IOP reduction. Conclusion: Switching to SofZia-preserved travoprost after BAK-preserved latanoprost resulted in a lower incidence of keratoconjunctival epitheliopathy, especially in the cornea, with no clinically relevant changes in hyperaemia and IOP.

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“…BAK-containing vehicle also did not cause histopathological changes in the eyeball, its accessory organs, and the nasal cavity with repeated applications up to 52 weeks and up to 8 times/day, and using concentrations up to 0.01%. There are several reasons why the concentration of 0.01%, at which BAK was deleterious in previous studies about the BAK-induced toxicity (Pfister and Burstein, 1976;Burstein, 1980;Tripathi and Tripathi, 1989;Tripathi et al, 1992;Becquet et al, 1998;De Saint Jean et al, 1999;Debbasch et al, 2000aDebbasch et al, , 2000bCha et al, 2004;Brasnu et al, 2008aBrasnu et al, , 2008bLi and Yan, 2008;Epstein et al, 2009;Pauly et al, 2009;Ammar et al, 2011;Ayaki and Iwasawa, 2011;Liang et al, 2011), was non-toxic in this study. One of the reasons could be because the concentration of the drug in the tear film following ocular application can be greatly affected by several factors.…”

Section: Discussionmentioning

confidence: 65%

“…Benzalkonium chloride (BAK) is the most widely used preservative in ophthalmic solutions. Ocular toxicity of BAK has been investigated by many in vitro experiments using cell culture systems, such as human corneal cell lines (Tripathi and Tripathi, 1989;Tripathi et al, 1992;Li and Yan, 2008;Epstein et al, 2009;Ammar et al, 2011), human conjunctival cell lines (De Saint Jean et al, 1999;Debbasch et al, 2000aDebbasch et al, , 2000bBrasnu et al, 2008aBrasnu et al, , 2008bEpstein et al, 2009;Ammar et al, 2011;Ayaki and Iwasawa, 2011), a three-dimensional model of human corneal epithelium (Pauly et al, 2009;Liang et al, 2011), rabbit corneal cell lines (Cha et al, 2004;Ayaki and Iwasawa, 2011), and bovine corneal cell lines (Ayaki and Iwasawa, 2011). In addition, the ocular toxicity of BAK has been investigated by several in vivo experiments following application on the ocular surface of rats (Becquet et al, 1998), rabbits (Pfister and Burstein, 1976;Burstein, 1980), and cats (Burstein, 1980).…”

Section: Introductionmentioning

confidence: 99%

Local toxicity of benzalkonium chloride in ophthalmic solutions following repeated applications

Okahara

Kawazu

2013

J. Toxicol. Sci.

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-We performed repeated toxicity studies of benzalkonium chloride (BAK)-containing vehicles of ophthalmic solutions in monkeys and rabbits to assess the local toxicity of BAK after repeated applications on the ocular surface. Local toxicity of BAK was evaluated by toxicity studies in which a 0.01% BAK-containing vehicle was applied twice/day for 52 weeks, 4 times/day for 39 weeks, or 6 times/day for 13 weeks, or in which a 0.005% BAK-containing vehicle was applied 6 times/day for 52 weeks or twice/day for 4 weeks in monkeys. Local toxicity of BAK was also evaluated where a 0.01% BAK-containing vehicle was applied 6 times/day for 6 weeks, or a 0.005% BAK-containing vehicle was applied twice/day for 39 weeks or 8 times/day for 4 weeks in rabbits. These doses were chosen because BAK is generally used at concentrations up to 0.01% in ophthalmic solutions. The BAK-containing vehicle did not cause ophthalmological changes suggestive of irritation, allergy, or corneal damage. We also did not observe any histopathological changes in the eyeball, eyelid, lacrimal gland, and nasal cavity, with repeated applications of BAK for up to 52 weeks, up to 8 times/day, or at concentrations up to 0.01%, in monkeys and rabbits. Our results suggest that BAK in concentrations up to 0.01% in ophthalmic solution is non-toxic to the eyeball, its accessory organs, and the nasal cavity after long repeated applications.

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Corneal epithelial cellular dysfunction from benzalkonium chloride (BAC) in vitro

Abstract: BAC can induce corneal epithelial dysfunction, which can damage the corneal epithelial barrier. This effect occurs when BAC is used frequently or for periods over 30 min, even when the BAC concentration is low (0.001%).

Cited by 151 publications

References 10 publications

Comparison of fluoroquinolones: cytotoxicity on human corneal epithelial cells

Comparison of fluoroquinolones: cytotoxicity on human corneal epithelial cells

Effects of SofZia‐preserved travoprost and benzalkonium chloride‐preserved latanoprost on the ocular surface – a multicentre randomized single‐masked study

Local toxicity of benzalkonium chloride in ophthalmic solutions following repeated applications

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