A Comparison of the Effects of Benzalkonium Chloride on Ocular Surfaces between C57BL/6 and BALB/c Mice

Yang, Qian; Zhang, Yafang; Liu, Xiuping; Wang, Nan; Song, Zhenyu; Wu, Kaili

doi:10.3390/ijms18030509

Cited by 37 publications

(33 citation statements)

References 35 publications

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“…It was assumed that the precipitate was formed because of the interaction between the protein in USL and benzalkonium chloride used as a protein precipitation agent [37]. Also, benzalkonium chloride had high cytotoxicity to conjunctival epithelial cells [38,39]. When conjunctival epithelial cells were incubated with 0.01%, 0.0033%, 0.0011%, 0.00037%, 0.00012%, and 0.000041% benzalkonium chloride for 12 h, cell viability was 7.7% ± 0.1%, 7.3% ± 0.4%, 10.3% ± 3.9%, 41.0% ± 7.4%, 79.0% ± 8.3%, and 93.8% ± 4.4%, respectively, and thus benzalkonium chloride was not considered as an additive in this study ( Figure S4).…”

Section: Long-term and Accelerated Testmentioning

confidence: 99%

Achyranthis radix Extract-Loaded Eye Drop Formulation Development and Novel Evaluation Method for Dry Eye Treatment

et al. 2020

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Recently, Achyranthis radix extract has been studied as a therapeutic agent for dry eye disease that occurs from fine dust. The aim of this study was the development of Achyranthis radix extract-loaded eye drop formulations using lubricants, generally used for artificial tear eye drops. Ecdysterone was used as a marker compound for Achyranthis radix extract and 1% Achyranthis radix extract solution contained 14.37 ± 0.04 μg/mL of ecdysterone. Before formulation studies, a new method was performed to evaluate pigmentation, which might be caused by eye drops of herbal extract. A comparative study of the water retention ability of each formulation and ability to prevent the death of conjunctival epithelial cells in dry conditions was conducted. Moreover, treatment of Achyranthis radix extract (USL) eye drop formulation exhibited a significant inhibitory effect on inflammation in a concentration-dependent manner. The long-term and accelerated stability tests showed that lubricants could contribute to the stability of herbal extracts in solution. In conclusion, hyaluronic acid showed a good effect on the development of eye drop formulation using Achyranthis radix extracts for treating dry eye disease.

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Section: Long-term and Accelerated Testmentioning

confidence: 99%

Achyranthis radix Extract-Loaded Eye Drop Formulation Development and Novel Evaluation Method for Dry Eye Treatment

et al. 2020

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“…15 Pharmacological intervention using topical atropine or benzalkonium chloride has been widely used with markedly varying results even between different rodent strains in the case of benzalkonium chloride. 16 The molecule causes corneal epithelial disruption, stromal neovascularisation, and infiltration of inflammatory cells that mimic those changes caused in dry eye but not through the same mechanisms. The muscarinic antagonist atropine sulphate does cause tear reduction in several laboratory animal models that have then been used to evaluate the efficacy of topical tear replacement.…”

Section: Models Of the Tear Film In Health And Diseasementioning

confidence: 99%

Optimising tear replacement rheology in canine keratoconjunctivitis sicca

Williams

2018

Eye

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Dry eye is a substantial problem in a large number of human and canine patients. Numerous laboratory models for tear deficiency exist using genetically predisposed rodent models, animals treated with topical anti-muscarinics, or those kept in environments with increased air flow to produce the ocular surface changes seen in human patients. Canine keratoconjunctivitis sicca, seen in many thousands of dogs kept as companion animals, can provide a valuable spontaneous model for testing tear replacement medications that might better model disease in human patients, existing as it does in an outbred population that live in the same environments as their owners. Here the development of a crosslinked hyaluronic acid topical drop is described together with the results of trials on dogs with spontaneous keratoconjunctivitis sicca. Although hyaluronic acid in its native form in tear replacement drops shows a Newtonian rheology, the crosslinked product described here behaves in a non-Newtonian manner, with the same shear thinning shown by the tear film itself. The crosslinked product thus shows itself as a potentially valuable tear replacement medication for the human dry eye population as well as for dogs with the same condition.

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“…Although BAC provides excellent antimicrobial properties in ophthalmic preparations, a large number of clinical and experimental investigations using in vitro or animal models suggested cytotoxic effects of even low BAC concentrations on several components of the eye (see [18]). The topical administration of BAC-containing eye drops may cause a variety of ocular surface changes, from ocular discomfort, redness, dryness, and tear film instability [19][20][21][22][23][24][25][26] to allergic, immune, inflammatory reactions [27][28][29], ocular irritation, scarring of the ocular surface with irreversible vision impairment [21,30,31], disruption of the blood-aqueous barrier inducing cystoid macular edema following cataract surgery [32,33], loss of goblet cells (see [27,34]) and, at higher concentrations, to the disruption of the corneal epithelium, induction of apoptosis or necrosis of Chang's conjunctival cells [31-33, 35, 36]. The proapoptotic effects were seen at very low concentrations of BAC with a threshold of toxicity found at about 0.005% (i.e., below the usual concentration used in most eye drops).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Dysfunctions May Be One of the Major Causative Factors Underlying Detrimental Effects of Benzalkonium Chloride

Рогов

Goleva

Sukhanova

et al. 2020

Oxidative Medicine and Cellular Longevity

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Benzalkonium chloride (BAC) is currently the most commonly used antimicrobial preservative in ophthalmic solutions, nasal sprays, and cosmetics. However, a large number of clinical and experimental investigations showed that the topical administration of BAC-containing eye drops could cause a variety of ocular surface changes, from ocular discomfort to potential risk for future glaucoma surgery. BAC-containing albuterol may increase the risk of albuterol-related systemic adverse effects. BAC, commonly present in personal care products, in cosmetic products can induce irritation and dose-dependent changes in the cell morphology. The cationic nature of BAC (it is a quaternary ammonium) suggests that one of the major targets of BAC in the cell may be mitochondria, the only intracellular compartment charged negatively. However, the influence of BAC on mitochondria has not been clearly understood. Here, the effects of BAC on energy parameters of rat liver mitochondria as well as on yeast cells were examined. BAC, being a "weaker" uncoupler, potently inhibited respiration in state 3, diminished the mitochondrial membrane potential, caused opening of the Ca2+/Pi-dependent pore, blocked ATP synthesis, and promoted H 2 O 2 production by mitochondria. BAC triggered oxidative stress and mitochondrial fragmentation in yeast cells. BAC-induced oxidative stress in mitochondria and yeast cells was almost totally prevented by the mitochondria-targeted antioxidant SkQ1; the protective effect of SkQ1 on mitochondrial fragmentation was only partial. Collectively, these data showed that BAC acts adversely on cell bioenergetics (especially on ATP synthesis) and mitochondrial dynamics and that its prooxidant effect can be partially prevented by the mitochondria-targeted antioxidant SkQ1.

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A Comparison of the Effects of Benzalkonium Chloride on Ocular Surfaces between C57BL/6 and BALB/c Mice

Cited by 37 publications

References 35 publications

Achyranthis radix Extract-Loaded Eye Drop Formulation Development and Novel Evaluation Method for Dry Eye Treatment

Achyranthis radix Extract-Loaded Eye Drop Formulation Development and Novel Evaluation Method for Dry Eye Treatment

Optimising tear replacement rheology in canine keratoconjunctivitis sicca

Mitochondrial Dysfunctions May Be One of the Major Causative Factors Underlying Detrimental Effects of Benzalkonium Chloride

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