https://doi.org/10.31288/oftalmolzh201448087

Effect of the preservative benzalkonium chloride eye drops on the state of mitochondrial enzymes tissues of the anterior eye

Senishin VI1, Rafalyuk SY2

1Lviv Regional Hospital

2Lviv National Medical University named after Danila Galitsky, Lviv (Ukraine)

Introduction. Despite the proven side effects caused by benzalkonium chloride (BAC), the worldwide most glaucoma patients continue to use eye drops containing this preservative, so the investigation by studying the effect of benzalkonium chlo­ride on the condition of the tissues of the anterior eye is important. Purpose. To study the effect of the preservative benzalkonium chloride eye drops on the state of mitochondrial enzymes tissues of the anterior eye. 

Material and methods. 34 rabbits were used for the experiment, they were divided into 3groups: group 1 — control (10 rabbits), group 2 — investigated (12 rabbits), treated with instillation of 0.02 % solution of BAC, group 3 — investigated (12 rabbits) which received 0.1 % solution of BAC. The cornea, conjunctiva and tear fluid were studied. The activity of mitochondrial enzymes (malate dehydrogenase, hlutamatdehidrohenazy, succinate dehydrogenase and cytochrome oxidase) was determined in the cornea, conjuctiva and tear fluid.

Results. The analysis of the results presented suggest that benzalkonium chloride in low (0.02 % solution) and higher (0.1 % solution) concentration cause expressive disturbance of oxidation of the biological substrates in the mitochondria tissues of the anterior eye. However, a clear dose-dependent effect of BAC was found only in relation to cytochrome oxidase — an enzyme localized outside the inner mitochon-drial membrane. At the same time, there was found no statistically significant dose dependence of enzymes that are localized at inside of the mitochondrial matrix (malate dehydrogenase, hlutamatdehidrohenazy, succinate dehydrogenase).

Conclusions. 1. Preservative eye drops BAC at the concentration of 0.02 and 0.1 % causes severe damage of the mitochondrial oxidative function of tissues of the anterior eye: the cornea, conjunctiva. 2. There was revealed a clear dose-dependentinhibitory effect on the enzyme BAC of the inner mitochondrial membrane — cyto-chrome oxidase.The enzyme activity in using higher concentrations of BAC in the cornea and conjunctiva decreased by 39.6 and 46.5 %, respectively.

Key words. Cornea, conjunctiva,  tear fluid, mitochondria enzymes   

References

1.     Gaidamaka TB, Senishin VI, Veliksar TA, Rafalyuk SYa.Study of pathochemical influence of contact lenses and eye drops preservatives on the structure of the anterior segment eye. Proceedings of XIII Ukrainian Congress of Ophthal­mologists, 21-23 May. Odessa; 2014. 9-10.

2.     Gaidamaka TB, Senishin VI. Influence of benzalconium chloride on activity of the oxidation-reduction enzymes in the tissues of the anterior eye. Oftalmol Zh. 2013;5:62-7. Russian.

3.     Ivanova NV. Preservatives in topic therapy of eye diseases: advantages and disadvantages. Oftalmologiia. Vostochnaia Evropa. 2013.1(6):2-7. Russian.

4.     Nasledov A. SPSS computer data analysis in psychology and social sciences. Spb.: Piter; 2005. 416 p.

5.     New methods of biochemical analysis. Izd. Leningradsk-ogo univer. 1991. 395 p.

6.     Petrov SYu, Safonova DM. Preservatives in ophthalmic preparations; from benzalconium chloride to polyquaternium. M.: Glaukoma. 2013;4:92-6. Russian.

7.     Ammar D. A, Noecker R. J, Kahook MY. Effects of benzalkonium chloride-preserved, polyquad-preserved, and sofZia-preserved topical glaucoma medications on human ocular epithelial cells. Adv. Ther. 2010;27:1-9.

8.     Ayaki M, Yaguchi S, Iwasawa A. Cytotoxicity of ophthalmic solution with and without preservatives to human corneal endothelial cells, epithelial cells and conjunctival epithelial cells. Clin. Exp. Ophthalmol. 2008;36:553-9.

9.     Barki WH, Tahir M. Effects of topical benzalkonium chlo­ride on corneal epithelium. Biomedica. 2007;23:65- 70.

10.  Baudouin C, Labbe A, Liang H. Preservatives in eyedrops: the good, the bad and the ugly. Prog. Retin. Eye Res.2010;29:312-34.

11.  Bergmeyer HV. Metoden der enzymatischen Analyse. Herausgegeben von H. U. Bergmeyer. Berlin;1986. 2220 p.

12.  De Saint Jean M, Brignole F, Bringuier A. Effects ofbenzalkonium chloride on growth and survival of Chang conjunctival cells. Invest. Ophthalmol. Vis. Sci. 1999;40:619-30.

13.  Hopes M, Broadway DC. Preservative-free Treatment in Glaucoma Is a Sensible and Realistic Aim for the Future.Europ. Ophthalmic. Review. 2010;4:23-8.

14.  Hughes EH, Pretorius M, Eleftheriadis H. Long-term recovery of the human corneal endothelium after toxic injury by benzalkonium chloride. Br. J. Ophthalmol. 2007;91:1460- 3.

15.  Khot-Reiter S, Jessen BA. Evaluation of the cytotoxic effects of ophthalmic solutions containing benzalkonium chloride on corneal epithelium using an organotypic 3-D model. BMC Ophthalmol. 2009;9:1471-5.

16.  Kim JR, Oh TH, Kim HS. Effect of benzalkonium chloride on the ocular surface of the rabbit. Jpn. J. Ophthalmol.2011;55:283-93.

17.  Lemp MA, Zimmerman LE. Toxic endothelial degeneration in ocular surface disease treated with topical medications containing benzalkonium chloride. Am. J. Ophthalmol. 1988;105:670-3.

18.  Liang H, Baudouin C, Pauly A. Conjunctival and corneal reactions in rabbits following short- and repeated exposure to preservative-free tafluprost, commercially avail­able latanoprost and 0,02 % benzalkonium chloride. Br.J. Ophthalmol. 2008;92:1275-82.

19.  Lin Z, Liu X, Zhou T. A mouse dry eye model induced by topical administration of benzalkonium chloride. Mol.Vis. 2011;17:257-64.

20.  Majumdara S, Hippalgaonkara K, Repka M. A. Effect of chitosan, benzalkonium chloride and ethylendiaminetet-raacetic acid on permeation of acyclovir across isolated rabbit cornea. Int. J. Pharm. 2008;348:175-8.

21.  Trocme S, Hwang L-J, Bean GW. The role of benzalkonium chloride in the occurrence of punctate keratitis: a meta-analysis of randomized, controlled clinical trials. Ann. Pharmacother. 2010;44:1914-21.

22.  Whitson JT, Cavanagh HD, Lakshman N. Assessment of corneal epithelial integrity after acute exposure to ocular hypotensive agents preserved with and without benzalkonium chloride. Adv. Ther. 2006;23:663-71.

23.  Wilson FM. Adverse external ocular effects of topical ophthalmic therapy: an epidemiologic, laboratory, and clinical study. Tr. Am. Ophth. Soc. 1983;19:854-8.

24.  Xiong C, Chen D, Liu J. A rabbit dry eye model induced by topical medication of a preservative benzalkonium chloride. Invest. Ophthalmol. Vis. Sci. 2008;49:1850-6.

25.  Ye J, Wu H, Zhang H. Role of benzalkonium chloride in DNA strand breaks in human corneal epithelial cells. Graefes Arch. Clin. Exp. Ophthalmol. 2011;249: 1681-7.