The effects of intravenous contrast substance administration on intraocular pressure, tear amount and oxidative stress in rats

Abstract

Although iodinated radiocontrast agents, which are frequently used in radiological procedures such as indirect radiography, angiography, intravenous urography and computed tomography, are generally safe, they can cause serious side effects. In this study, it was aimed to investigate the effect of intravenous ionic high osmolar contrast agent administration on intraocular pressure, tear amount and oxidant and antioxidant parameters of eye tissue. Study groups consisted of 2 groups, Group 1 (Control) and Group 2 (Urographin), and a total of 16 Wistar albino female rats were used. On the first day of the experiment, 6 ml/kg of physiological saline was administered intravenously to the control group, and the same dose of contrast agent was administered to group 2. Intraocular pressure and tear amounts were measured at 1, 6, 12, 24 and 48 hours after intravenous administration. After measurements were made at the 48th hour of the experiment, all rats were euthanized and their eye tissues were removed. In order to reveal the oxidative damage and antioxidant activity in the eye tissue, malondialdehyde and reduced glutathione levels, catalase and glutathione peroxidase enzyme activities were measured spectrophotometrically. Schimer tear test (STT-1) strip was used for tear amount measurements, and rebound tonometer Tonovet® was used as tonometer for intraocular pressure measurements. No statistically significant difference was found between the control and urographin groups in terms of intraocular pressure and tear amounts in the measurements performed at 1,6,12,24 and 48th hours after urographin administration. It was observed that the same application significantly increased the malondialdehyde level (P<0.005) in the eye tissue. There was no significant difference between the groups in terms of reduced glutathione level and catalase and glutathione peroxidase enzyme activities in eye tissue. It was evaluated that intravenous contrast agent administration causes oxidative stress in the eye tissue and this may have a long-term ocular effect

Keywords

• Contrast agent
• eye
• oxidative stress

Ratlarda intravenöz kontrast madde uygulamasının göz içi basıncı, göz yaşı miktarı ve oksidatif stres üzerine etkileri

Öz

Endirekt radyografi, anjiyografi, intravenöz ürografi ve bilgisayarlı tomografi gibi radyolojik prosedürlerde sıklıkla kullanılmakta olan iyotlu radyo konrast ajanlar genellikle güvenli olmalarına rağmen ciddi yan etkilere sebep olabilmektedir. Bu çalışmada intravenöz iyonik yüksek ozmolar kontrast madde uygulamasının göz içi basıncı, göz yaşı miktarı ve göz dokusu oksidan ve antioksidan parametreler üzerindeki etkisinin araştırılması amaçlandı. Çalışma grupları Grup 1 (Kontrol) ve Grup 2 (Ürografin) olmak üzere 2 gruptan oluştu ve toplamda 16 adet wistar albino ırkı dişi rat kullanıldı. Denemenin ilk günü kontrol grubuna intravenöz olarak 6 ml/kg dozda serum fizyolojik, grup 2’ye ise aynı dozda kontrast madde uygulaması yapıldı. İntravenöz uygulamalardan sonraki 1, 6, 12, 24 ve 48. saatlerde göz içi basıncı ve gözyaşı miktarları ölçüldü. Denemenin 48. saatinde ölçümler yapıldıktan sonra bütün ratlar ötanazi edildi ve göz dokuları çıkarıldı. Göz dokusunda oksidatif hasar ve antioksidan aktivite durumunu ortaya koyabilmek için malondialdehit ve redükte glutatyon düzeyleri ile katalaz ve glutatyon peroksidaz enzim aktivitelerine spektrofotometrik olarak bakıldı. Göz yaşı miktarı ölçümlerinde schimer tear test (STT-1) stripi, göz içi basıncı ölçümlerinde ise tonometre olarak rebound tonometre Tonovet® kullanıldı. Ürografin uygulamasından sonraki 1, 6, 12, 24 ve 48. saatlerde yapılan ölçümlerde kontrol ve ürografin grupları arasında göz içi basıncı ve gözyaşı miktarları açısından istatistiki olarak anlamlı bir farklılık saptanmadı. Aynı uygulamanın göz dokusunda malondialdehit düzeyini (P<0,005) anlamlı şekilde arttırdığı görüldü. Göz dokusu redükte glutatyon düzeyi ile katalaz ve glutatyon peroksidaz enzim aktiviteleri açısından gruplar arasında anlamlı bir farklılık tespit edilemedi. İntarvenöz kontrast madde uygulamasının göz dokusunda oksidatif strese neden olduğu ve bunun da uzun sürede oküler etkisinin olabileceği değerlendirildi.

Anahtar Kelimeler

• Kontrast madde
• göz
• oksidatif stres.

References

1. Aebi, H. E. (1983). Catalase. Methods of enzymatic analysis. 673-686.
2. Agmon, Y., Peleg, H., Greenfeld, Z., Rosen, S., & Brezis, M. (1994). Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat. The Journal of Clinicial Investigation, 94(3), 1069-1075.
3. Akyol, S., Ugurcu, V., Altuntas, A., Hasgul, R., Cakmak, O., & Akyol, O. (2014). Caffeic acid phenethyl ester as a protective agent against nephrotoxicity and/or oxidative kidney damage: a detailed systematic review. The Scientific World Journal, 2014, 561971. doi: 10.1155/2014/561971. Epub 2014 Jun 3.
4. Başarslan, F., Yilmaz, N., Davarci, I., Akin, M., Ozgur, M., Yilmaz, C., & Ulutas, K. T. (2013). Effects of ebselen on radiocontrast media-induced hepatotoxicity in rats. Toxicology and İndustrial Health, 29(8), 746-752. doi: 10.1177/0748233712442730.
5. Baudouin, C., Irkec, M., Messmer, E. M., Benitez, Del Castillo, J. M., Bonini, S., Figueiredo, F. C., Geerling, G., Labetoulle, M., Lemp, M., Rolando, M., Setten, G. V., Aragona, P., & Odissey, E. C. G. (2018). Clinical impact of inflammation in dry eye disease: proceedings of the oddisey group meeting. Acta Ophthalmol, 96(2), 111-119.
6. Choi, W., Lian, C., Ying, L., Kim, G. E., You, I. C., Park, S. H., & Yoon, K. C. (2016). Expression of lipid peroxidation markers in the tear film and ocular surface of patients with non-Sjogren syndrome: potential biomarkers for dry eye disease. Current Eye Reearch, 41(9), 1143–1149.
7. Cintaş, D., İlem Özdemir, D., & Aşıkoğlu, M. (2019). Kontrast maddeler. Türk Farmakope Dergisi, 4(3), 129-138.
8. Dogru, M., Kojima, T., Simsek, C., & Tsubota, K. (2018). Potential role of oxidative stress in ocular surface inflammation and dry eye disease. Investigative Ophthalmol & Visula Science, 59(14), 163-168.

9. Draper, C. E., Adeghate, E., Lawrence, P. A., Pallot, D. J., Garner, A., & Singhet, J. (1998). Age-related changes in morphology and secretory responses of male rat lacrimal gland. Jurnal of the Automic Nervous System, 69(2-3), 173–183.
10. Fahy, E. T., Chrysostomou, V., & Crowston, J. G. (2016). Mini-review: impaired axonal transport and glaucoma. Current Eye Research, 41(3), 273–283.
11. Fine, H. F., Biscette, O., Chang, S., & Schiff, W. M. (2007). Ocular hypotony: a review. Comprehensive Ophthalmol Uptade, 8(1), 29–37.
12. Ghaffari, M. S., Malmasi, A., & Bokaie, S. (2010). Effect of acepromazine or xylazine on tear production as measured by Schirmer tear test in normal cats. Veterinary Ophthalmology, 13(1), 1-3.
13. Goel, M., Picciani, R. G., Lee, R. K., & Bhattacharya, S. K. (2010). Aqueous humor dynamics: a review. Open Ophthalmology Journal, 4, 52-59. doi: 10.2174/1874364101004010052.
14. İşler, C. T., Altuğ M. E., Kılıç, S. (2013). Evaluation of tear fluid secretion and intraocular pressure in normal merinos sheepand saanen goats. Revue de Medecine Veterinaire, 5, 278-282.
15. Jabbehdari, S., Chen, J. L., & Vajaranant, T. S. (2021). Effect of dietary modification and antioxidant supplementation on intraocular pressure and open-angle glaucoma. European Journal of Ophthalmol, 31(4), 1588-1605. doi: 10.1177/1120672120960337.
16. Jensen, S. J. K. (2003). Oxidative stress and free radicals. Journal of Molecular Structure: THEOCHEM, 666, 387-392.
17. Johnson, M. (2006). What controls aqueous humour outflow resistance? Experimental Eye Research, 82(4), 545–557.
18. Kanda, T., Kajiyama, A., Morimitsu, W., Nishino, Y., Oishi, Y., Shimizu, Y., Maeta, N., Furumoto, K., Itoh, Y., & Furukawa, T. (2019). Effect of medetomidine on tear flow measured by Schirmer tear test I in normal pigs. Journal of Veterinary Medical Science, 81(4), 538–540. https://doi.org/10.1292/jvms.18-0660.
19. Kepner, A. M., Bacasnot, J. V., & Stahlman, B. A. (2012). Intravenous contrast alone vs intravenous and oral contrast computed tomography for the diagnosis of appendicitis in adult ED patients. The American Journal of Emergency Medicine, 30(9), 1765-1773. doi: 10.1016/j.ajem.2012.02.011.
20. Kim, J., Kim, N. S., Lee, K. C., Lee, H. B., Kim, M. S., & Kim, H. S. (2013). Effect of topical anesthesia on evaluation of corneal sensitivity and intraocular pressure in rats and dogs. Veterinary Ophthalmology, 16(1), 43-46.
21. Knox, D. L., Eagle Jr, R. C., & Green, W. R. (2007). Optic nerve hydropic axonal degeneration and blocked retrograde axoplasmic transport: histopathologic features in human high-pressure secondary glaucoma. Archives of Ophthalmology, 125(3), 347–353.
22. Lawrence, R. A., & Burk, R. F. (1976). Glutathione peroxidase activity in selenium-deficient rat liver. Biochemical and Biophysical Research Communications,71(4), 952-958.
23. Leonardi, F., Costa, G. L., Dubau, M., Sabbioni, A., Simonazzi, B., & Angelone, M. (2020). Effects of intravenous romifidine, detomidine, detomidine combined with butorphanol, and xylazine on tear production in horses. Equine Veterinary Education, 32, 53-57.
24. Lightfoot, C. B., Abraham, R. J., Mammen, T., Abdolell, M., Kapur, S., & Abraham, R. J. (2009). ‘Survey of radiologists’ knowledge regarding the management of severe contrast material-induced allergic reactions, Radiology, 251(3), 691–696.
25. Lowry, O., Rosebrough, N., Farr, A. L., & Randall, R. (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193(1), 265-275.
26. Lozano, D. C., Hartwick, A. T., & Twa, M. D. (2015). Circadian rhythm of intraocular pressure in the adult rat. Chronobiol International, 32(4), 513–523.
27. Margadant, D. L., Kirkby, K., Andrew, S. E., & Gelatt, K. N. (2003). Effect of topical tropicamide on tear production as measured by Schirmer’s tear test in normal dogs and cats. Veterinary Ophthalmology, 6(4), 315–320.
28. Mermoud, A., Baerveldt, G., Minckler, D. S., Lee, M. B., & Rao, N. A. (1994). Intraocular pressure in Lewis rats. Investigative ophthalmology & Visual Science, 35(5), 2455-60.
29. Modi, N., Jain, S., Tilkar, M. & Sarkar, N. C. (2016). Ocular myasthenia gravis: Side effect of urografin. Heart India, 4(1), 29.
30. Morita, J., Yamashita, H., Sugihara, K., Wakamatsu, M., & Sasaki, M. (2020). Spontaneous ocular abnormalities in sprague–dawley rats. Comparative Medicine, 70(2), 140-144.
31. Morrison, J. C., Guo, W. O. C. Y., & Johnson, E. C. (2011). Pathophysiology of human glaucomatous optic nerve damage: insights from rodent models of glaucoma. Exp. Eye Research, 93(2), 156–164.
32. Myers, S. I., Wang, L., Liu, F., & Bartula, L. L. (2006). Iodinated contrast induced renal vasoconstriction is due in part to the downregulation of renal cortical and medullary nitric oxide synthesis. Journal of Vascular Surgery, 44(2), 383-91.
33. Nazzaro, P., Baranello, S., Corvinelli, M., Di Cienzo, G., Salvatore, A. M., & Brigante, M. (2013). Iodide mumps following low-osmolarity contrast medium use in haemodialysis patients. Giornale Italliano Nefrologia. 30(1).
34. Özbek, K., Ceyhan, K., Koç, F., Söğüt, E., Altunkaş, F., Karayakalı, M., Çelik, A., Kadı, H., Köseoğlu R. D., & Önalan O. (2015). The protective effect of single dose tadalafil in contrast-induced nephropathy: An experimental study. Anatolian Journal of Cardiology, 15(4), 306-310. DOI:10.5152/akd.2014.5380.
35. Pease, M. E., McKinnon, S. J., Quigley, H. A., Kerrigan Baumrind, L. A., & Zack, D. J. (2000). Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma. Investigative Ophthalmology & Visual Science, 41(3), 764–774.
36. Persson, P. B. (2005). Contrast medium-induced nephropathy. Nephrology Dialysis Transplantation, 20(1), i1.
37. Pinazo Duran, M. D., Gallego Pinazo, R., Garcia-Medina, J. J., Zanon Moreno, V., Nucci, C., Dolz Marco, R., Martinez Castillo, S., Galbis Estrada, C., Marco Ramirez, C., Lopez Galvez, M. I., Galarreta, D. J., & Diaz Lopis, M. (2014). Oxidative stress and its downstream signaling in aging eyes. Clinicial Interventions in Aging, 9, 637–652.
38. Placer, Z. A., Cushman, L. L., & Johnson, B. C. (1966). Estimation of product of lipid peroxidation (malonyldialdehyde) in biochemical systems. Analytical Biochemistry, 16(2), 359–364.
39. Reuter, S., Gupta, S. C., Chaturvedi, M. M., & Aggarwal, B. B. (2010). Oxidative stress, inflammation, and cancer: how are they linked? Free Radical Biology Medicine, 49(11), 16031616.
40. Rios, J. D., Horikawa, Y., Chen, L. L., Kublin, C. L., Hodges, R. R., Dartt, D. A., & Zoukhri, D. (2005). Agedependent alterations in mouse exorbital lacrimal gland structure, innervation and secretory response. Experimental Eye Res, 80(4), 477–491.
41. Rodrigues, B. D., Montiani-Ferreira, F., Bortolini, M., Somma, A. T., Komáromy, A. M, & Dornbusch, P. T. (2021). Intraocular pressure measurements using the TONOVET rebound tonometer: Influence of the probe-cornea distance. Veterinary Ophthalmology, 24, 175-185. https://doi.org/10.1111/vop.12832.
42. Salinas-Navarro, M., Alarcon-Martinez, L., Valiente-Soriano, F. J., Jiménez-López, M., Mayor-Torroglosa, S., Avilés-Trigueros, M., Villegas-Pérez, M. P., & Vidal-Sanz, M. (2010). Ocular hypertension impairs optic nerve axonal transport leading to progressive retinal ganglion cell degeneration. Experimental Eye Reseach, 90, 168–183. doi: 10.1016/j.exer.2009.10.003. Epub 2009 Oct 14.
43. Sanchez, R. F., Mellor, D., & Mould, J. (2006). Effects of medetomidine and medetomidine‐butorphanol combination on Schirmer tear test 1 readings in dogs. Veterinary Ophthalmology, 9(1), 33-37.
44. Sedlak, J., & Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Analytical Biochemistry, 25, 192-205.
45. Sharma, S., Kaul, U., & Rajani M. (1990). The spectrum of isolated ocular reactions following intravascular contrast administration. Indian Heart Journal, 42(6), 455-456.
46. Sheriff, M. H., Abas A. M., & Zaitoun, L. A. (2018). Protective effect of ginger extract against contrast media-induced nephrotoxicity in rats. Biochemistry letters, 14(1), 202-222.
47. Sies, H. (2018). On the history of oxidative stress: Concept and some aspects of current development. Current Opinion in Toxicology, 7,122-126.
48. Sies, H., Berndt, C., & Jones, D. P. (2017). Oxidative stress. Annual Review of Biochemistry, 86, 715–748.
49. Sutcuoglu, O., Derici, M. K., Pasaoglu, O. T., Dumludağ, B., Helvacı, O., Öğüt, B., Gönül, I. I., & Derici, U. (2019). Is it possible to prevent contrast-induced nephropathy with dexpanthenol? International Urology and Nephrology, 51(8), 1387–1394. https://doi.org/10.1007/s11255-019-02194-2.
50. Tangvarasittichai, O., & Tangvarasittichai, S. (2018). Oxidative stress, ocular disease and diabetes retinopathy. Current Pharmaceutial Design, 24(40), 4726-4741.
51. Thomson, K. R., & Varma, D. K. (2010). Safe use of radiographic contrast media. Australian Prescriber, 33(1), 19–22.
52. Ung, L., Pattamatta, U., Carnt, N., Wilkinson-Berka, J. L., Liew, G., & White, A. J. R. (2017). Oxidative stress and reactive oxygen species: a review of their role in ocular disease. Clinicial Science, 131(24), 2865-2883.
53. Valderram, C. M., Li, R., & Liu, J. H. (2008). Direct effect of light on 24h variation of aqueous humor protein concentration in sprague dawley rats. Experimental Eye Research, 87(5), 487–491.
54. Wu, Y. W., Leow, K. S., Zhu, Y., & Tan, C. H. (2016). Prevention and management of adverse reactions induced by iodinated contrast media. Annals Academy of Medicine Singapore, 45(4), 157-164.
55. Yakan, S., İşler, C. T., & Denk, H. (2021). determination of ıntraocular pressure in clinically healthy Turkish eastern anatolian red cattle of different age groups using rebound tonometry. Israel Journal of Veterinary Medicine, 76 (4), 8-13.
56. Yarosz, E. L., & Chang, C. H. (2018). The role of reactive oxygen species in regulating T cell-mediated immunity and disease. Immune Netw, 18, e14.
57. Yesildağ, A., Ozden, A., Yilmaz, H. R., Uz, E., Ağackiran, Y., Mihrican, Yesildağ, M., Yilmaz, N., Sirmali, R., Vural, H., & Naziroğlu, M. (2009). Erdosteine modulates radiocontrast-induced hepatotoxicity in rat. Cell Biochemistry and Function, 27, 142-147.
58. Zhao, Q., Yin, J., Lu, Z., Kong, Y., Zhang, G., Zhao, B., & Wang, F. (2016). Sulodexide protects contrast-induced nephropathy in sprague dawley rats. Cellular Physiology and Biochemistry, 40(3-4), 621–632.