Abstract
Eye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers (IL-1α, IL-1β, IL-8 and TNF-α) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenario.
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Hopkins, G.A. and Lyle, W.M. (1977) Potential systemic effects of six common ophthalmic drugs. J. Am. Optom. Assoc., 48, 1241–1245.
Leader, B.J. and Calkwood, J.C. (1996) Peril to the nerveglaucoma and clinical neuro-opthalmology. Kugler publications, New Orleans, pp. 65–70.
Gray, C. (2006) Systemic toxicity with topical ophthalmic medications in children. Paediatr. Perinat. Drug Ther., 7, 23–29.
Salminen, L. (1990) Review: systemic absorption of topically applied ocular drugs in humans. J. Ocul. Pharmacol. Ther., 6, 243–249.
Draize, J.H., Woodard, G. and Calvery, H.O. (1944) Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J. Pharmacol. Exp. Ther., 82, 377–390.
Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951) Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193, 265–275.
Okhawa-Matsumoto, A. and Fridovich, I. (2001) Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu-, Zn-SOD in mitochondria. J. Biol. Chem., 276, 38388–38393.
Moron, M.S., Depierre, J.W. and Mannervik, B. (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim. Biophys. Acta, 582, 67–78.
Mize, C.E. and Langdon, R.G. (1962) Hepatic glutathione reductase: purification and general kinetic properties. J. Biol. Chem., 237, 1589–1595.
Rotruck, J.T., Pope, A.L., Ganther, H.E., Swanson, A.B., Hafeman, D.G. and Hoekstra, W.G. (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science, 179, 588–590.
Marklund, S. and Marklund, G. (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem., 47, 469–474.
Kim, Y.C., Chiang, B., Wu, X. and Prausnitz, M.R. (2014) Ocular delivery of macromolecules. J. Controlled Release, 190, 172–181.
Urtti, A. (2006) Challenges and obstacles of ocular pharmaco-kinetics and drug delivery. Adv. Drug Delivery Rev., 58, 1131–1135.
Yi, X., Wang, Y. and Yu, F.S. (2000) Corneal epithelial tight junctions and their response to lipopolysaccharide challenge. Invest. Ophthalmol. Visual Sci., 41, 4093–4100.
Green, K., Bowman, K.A., Elijah, R.D., Mermelstein, R. and Kilpper, R.W. (1985) Dose-effect response of the rabbit eye to cetylpyridinium chloride. Cutaneous Ocul. Toxicol., 4, 13–26.
Takahashi, Y., Koike, M., Honda, H., Ito, Y., Sakaguchi, H., Suzuki, H. and Nishiyama, N. (2008) Development of the short time exposure (STE) test: An in vitro eye irritation test using SIRC cells. Toxicol. In Vitro, 22, 760–770
Spielmann, H., Kalweit, S., Liebsch, M., Wirnsberger, T., Gerner, I., Bertram-Neis, E. Krauser, K., Kreiling, R., Miltenburger, H.G., Pape, W. and Steiling, W. (1993) Validation study of alternatives to the Draize eye irritation test in Germany: Cytotoxicity testing and HET-CAM test with 136 industrial chemicals. Toxicol. In Vitro, 7, 505–510.
Bagley, D.M., Gardner, J.R., Holland, G., Lewis, R.W., Vrijhof, H. and Walker, A.P. (1999) Eye Irritation: Updated reference chemicals data bank. Toxicol. In Vitro, 13, 505–510.
Wang, F.H., Chen, M., Liu, T., Zang, X.J., Gong, H.Q. and Shi, W.Y. (2012) Lymphocyte infiltration and activation in iris-ciliary body and anterior chamber of mice in corneal allograft rejection. Int. J. Ophthalmol., 5, 681–686.
Weng, J., Mohan, R.R., Li, Q. and Wilson, S.E. (1997) IL-1 upregulates keratinocyte growth factor and hepatocyte growth factor mRNA and protein production by cultured stromal fibroblast cells: Interleukin-1 beta expression in the cornea. Cornea, 16, 465–471.
Wilson, S.E., Mohan, R.R., Mohan, R.R., Ambrósio, R. Jr., Hong, J. and Lee, J. (2001) The corneal wound healing response: cytokine-mediated interaction of the epithelium, stroma, and inflammatory cells. Prog. Retinal Eye Res., 20, 625–637.
Ferrick, M.R., Thurau, S.R., Oppenheim, M.H., Herborf, C.P., Ni, M., Zachariae, C.O., Marsushima, K. and Chan, C.C. (1991) Ocular inflammation stimulated by intravitreal interleukin-8 and interleukin-1. Invest. Ophthalmol. Visual Sci., 32, 1534–1539.
Miller, M.D. and Krangel, M.S. (1992) Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit. Rev. Immunol., 12, 17–46.
Reddy, M.P., Webb, E.F., Cassatt, D., Maley, D., Lee, J.C., Griswold, D.E. and Truneh, A. (1994) Pyridinyl imidazoles inhibit the inflammatory phase of delayed type hypersensitivity reactions without affecting T-dependent immune responses. Int. J. Immunopharmacol., 16, 795–804.
Melo, A., Monteiro, L., Lima, R.M., Oliveira, D.M., Cerqueira, M.D. and El-Bachá, R.S. (2011) Oxidative stress in neurodegenerative diseases: mechanisms and therapeutic perspectives. Oxid. Med. Cell. Longevity, 2011, 467180.
Reuter, S., Gupta, S.C., Chaturvedi, M.M. and Aggarwal, B.B. (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Radical Biol. Med., 49, 1603–1616.
Yin, H., Xu, L. and Porter, N.A. (2011) Free radical lipid peroxidation: mechanisms and analysis. Chem. Rev., 111, 5944–5972.
Circu, M.L. and Aw, T.Y. (2010) Reactive oxygen species, cellular redox systems and apoptosis. Free Radical Biol. Med., 48, 749–762.
Rall, T.W. and Lehninger, A.L. (1952) Glutathione reductase of animal tissues. J. Biol. Chem., 194, 119–130.
Sastre, J., Palladro, F.V. and Viña, J. (2005) Glutathione. Handb. Environ. Chem., 20, 91–108.
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Reshma, C.S., Sruthi, S., Syama, S. et al. Assessing the Systemic Toxicity in Rabbits after Sub Acute Exposure to Ocular Irritant Chemicals. Toxicol Res. 31, 49–59 (2015). https://doi.org/10.5487/TR.2015.31.1.049
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DOI: https://doi.org/10.5487/TR.2015.31.1.049