Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats

Taskiran, Dilek; AFRASHİ, Filiz; DEĞİRMENCİ, Cumali; Aktug, Huseyin; erbas, oytun

Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats

Cumali DEĞİRMENCİ, (Ege Üniversitesi, Tıp Fakültesi, Göz Hastalıkları, İzmir, Türkiye)

Filiz AFRASHİ, (Ege Üniversitesi, Tıp Fakültesi, Göz Hastalıkları, İzmir, Türkiye)

Oytun ERBAŞ, (İstanbul Bilim Üniversitesi, Fizyoloji, İstanbul, Türkiye)

Hüseyin AKTUĞ, (Ege Üniversitesi, Tıp Fakültesi, Histoloji ve Embriyoloji, İzmir, Türkiye)

Dilek TAŞKIRAN (Ege Üniversitesi, Tıp Fakültesi, Fizyoloji, İzmir, Türkiye)

Retina-Vitreus

1 0

Yıl: 2019 Cilt: 28 Sayı: 2 Sayfa Aralığı: 219 - 224 Metin Dili: İngilizce İndeks Tarihi: 14-10-2020

Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats

Öz:

Purpose: To investigate the possible vascular endothelial growth factor inhibition effects of edaravone and to compare bevacizumab on diabetic retinopathy in streptozotocin-induced diabetic rats.Materials and Methods: Thirty-six adult male Sprague Dawley rats were used in the study. Diabetes was induced with streptozotocin (60mg/kg). After 4 weeks of treatment, the rats were euthanized and blood samples were collected for vascular endothelial growth factor assay.Additionally, enucleation was performed for vascular endothelial growth factor immunohistochemistry and outer nuclear layer measurements.Results: Treatments with both bevacizumab and edaravone signifi cantly decreased outer nuclear layer thickness and retinal vascular endothelialgrowth factor expression compared to serum physiologic groups. In addition, plasma vascular endothelial growth factor levels were signifi cantlyreduced in both bevacizumab and edaravone treated groups compared to the serum physiologic group.Conclusions: Intraperitoneal and intravitreal bevacizumab and intraperitoneal ederavone could diminish the progression of diabetic retinopathy.These fi ndings suggest that edaravone may become one of the therapeutic candidates of diabetic retinopathy in the future.

Anahtar Kelime:

Streptozotosin ile İndüklenmiş Diyabetik Sıçanlarda Edaravonun Retinopati Üzerine Olan Terapötik Etkileri

Öz:

Amaç: Streptozotosin ile diabet oluşturulan sıçanlarda diyabetik retinopatide edaravonun olası vasküler endotelyal growth faktör inhibe edici etkisinin araştırılması ve bevacizumab ile karşılaştırılması. Materyal ve Metod: Bu çalışmada 36 adet Sprague Dawley erkek sıçan kullanılmıştır. Diyabet streptozotosin (60 mg/kg) ile oluşturuldu. Sıçanlara 6 gruba ayrılarak intravitreal veya intraperitoneal olarak edaravone, bevacizumab ve serum fi zyolojik uygulandı. Dört haftalık tedavinin ardından, sıçanlara ötenazi yapıldı ve vasküler endotelyal growth faktör değerlendirmesi için kan örnekleri alındı. Ek olarak, vasküler endotelyal growth faktörün immünhistokimyasal olarak değerlendirilmesi ve dış nükleer tabakanın değerlendirilmesi için enükleasyon yapıldı. Bulgular: Bevacizumab ve edaravone tedavileri ile dış nükleer tabaka kalınlığında ve vasküler endotelyal growth faktör immünhistokimayasal değerlendirmesinde serum fi zyolojik grubu ile karşılaştırıldığında belirgin azalma mevcuttu. Ayrıca, kan vasküler endotelyal growth faktör seviyelerinde bevacizumab ve edaravone ile tedavi edilen gruparda serum fi zyolojik ile tedavi edilen grup ile karşılaştırıldığında belirgin azalma vardı. Sonuç: İntravitreal ve intraperitoneal bevacizumab ile intraperitoneal edaravone diyabetik retinopatinin ilerlemesini yavaşlatabilirler. Bu bulgular edaravonun gelecekte diyabetik retinopati tedavisinde bir aday olabileceğini düşündürtmektedir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Bibliyografik

1. Kowluru RA, Chan P-S. Oxidative stress and diabetic retinopathy. Exp Diabetes Res. 2007;2007:43603.
2. Madsen-Bouterse SA, Kowluru RA. Oxidative stress and diabetic retinopathy: pathophysiological mechanisms and treatme nt perspectives. Rev Endocr Metab Disord. 2008; 9:315-27.
3. Scott IU, Edwards AR, Beck RW et al. Network DRCR. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthal mology. 2007; 114:1860-7.
4. Yuan D, Xu Y, Hang H et al. Edaravone protect against retinal damage in streptozotocin-induced diabetic mice. PLoS One. 2014; 9:e99219.
5. Lu F, Adelma n RA. Are intravitreal bevacizumab and ranibizumab effective in a rat model of choroidal neovascularization? Graefes Arch Clin Exp Ophthalm ol. 2009; 247:171-7.
6. Maeno T, Tano R, Takenaka H et al. Edaravone (MCI-186) is effective as a free radical scavenger following arteriovenous sheathotomy for treatment of ma cular oedema associated with branch retinal vein occlusion. Br J of Ophthalmol. 2009; 93:1479- 82.
7. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010; 107:1058-70.
8. Toyoda K, Fujii K, Kamouchi M et al.Free radical s cavenger, edaravone, in stroke with internal carotid artery occlusion. J Neurol Sci. 2004; 221:11-17.
9. Uchiyama M, Tojo K, Yazawa T et al. Edaravone prevents lung injury induced by hepatic ischemia-reperfusion. J Surg Res. 2015; 194:551-7.
10. Shang H, Cui D, Yang D et al. The radical scavenger edaravone improves neurologic function and perihematomal glucose metabolism after acute intracereb ral hemorrhage. J Stroke Cerebrovasc Dis. 2015; 24:215-22.
11. Zhang T, Li Z, Dong J et al. Edaravone promotes functional recovery after mechanical peripheral nerve injury. Neural Regen Res. 2014; 9:1709-15.
12. Higashi Y, Jitsuiki D, Chayama K et al. Edaravone (3-methyl1-phenyl-2-pyrazolin-5-one), a novel free radical scavenger, for treatment of cardiovascular diseases. Recent Pat Cardiovasc Drug Discov. 2006; 1:85-93.
13. Mancino R, Di Pierro D, Varesi C et al. Lipid peroxidation and total antioxidant capacity in vitreous, aqueous humor, and blood samples from patients with diabetic retinopathy. Mol Vis. 2011; 17:1298-304.
14. Kowluru RA, Kanwar M, Chan PS et al. Inhibition of retinopathy and retinal metabolic abnormalities in diabetic rats with AREDSbased micronutrients. Arch Ophthalmol. 2008; 126:1266-72.
15. Semeraro F, Cancarini A, dell’Omo R et al. Diabetic Retinopathy: Vascular and Infl ammatory Disease. J Diabetes Res. 2015; 2015:582060.
16. Caldwell RB, Bartoli M, Behzadian MA et al. Vascular endothelial growth factor and diabetic retinopathy: role of oxidative stress. Curr Drug Targets. 2005; 6:511-24.
17. Lu M, Kuroki M, Amano S et al. Advanced glycation end products increase retinal vascular endothelial growth factor expression. J Clin Invest. 1998; 101:1219-24.
18. Clarke M, Dodson PM. PKC inhibition and diabetic microvascular complications. Best Pract Res Clin Endocrinol Metab. 2007; 21:573-86.
19. Stitt AW, Bhaduri T, McMullen CB et al. Advanced glycation end products induce blood-retinal barrier dysfunction in normoglycemic rats. Mol Cell Biol Res Commun. 2000;3:380-8.
20. Yamagishi S, Nakamura K, Matsui T et al. Pigment epitheliumderived factor inhibits advanced glycation end product-induced retinal vascular hyperpermeability by blocking reactive oxygen species-mediated vascular endothelial growth factor expression. J Biol Chem. 2006;281:20213-20.
21. Kikuchi K, Tancharoen S, Takeshige N et al. The effi cacy of edaravone (radicut), a free radical scavenger, for cardiovascular disease. Int J Mol Sci. 2013;14:13909-30.
22. Zhang N, Komine-Kobayashi M, Tanaka R et al. Edaravone reduces early accumulation of oxidative products and sequential infl ammatory responses after transient focal ischemia in mice brain. Stroke. 2005;36:2220-5.
23. Song Y, Gong YY, Xie ZG et al. Edaravone (MCI-186), a free radical scavenger, attenuates retinal ischemia/reperfusion injury in rats. Acta Pharmacol Sin. 2008;29:823-8.
24. Niiya Y, Abumiya T, Yamagishi S et al. Advanced glycation end products increase permeability of brain microvascular endothelial cells through reactive oxygen species-induced vascular endothelial growth factor expression. J Stroke Cerebrovasc Dis. 2012; 21:293- 8.
25. Zhang P, Li W, Li L et al. Treatment with edaravone attenuates ischemic brain injury and inhibits neurogenesis in the subventricular zone of adult rats after focal cerebral ischemia and reperfusion injury. Neuroscience. 2012; 201:297-306.
26. Masuda T, Shimazawa M, Hara H. Retinal Diseases Associated with Oxidative Stress and the Effects of a Free Radical Scavenger (Edaravone). Oxid Med Cell Longev. 2017;2017:9208489.
27. Inokuchi Y, Imai S, Nakajima Yet al. Edaravone, a free radical scavenger, protects against retinal damage in vitro and in vivo. J Pharmacol Exp Ther. 2009;329:687-98.

APA	DEĞİRMENCİ C, AFRASHİ F, erbas o, Aktug H, Taskiran D (2019). Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats. , 219 - 224.
Chicago	DEĞİRMENCİ Cumali,AFRASHİ Filiz,erbas oytun,Aktug Huseyin,Taskiran Dilek Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats. (2019): 219 - 224.
MLA	DEĞİRMENCİ Cumali,AFRASHİ Filiz,erbas oytun,Aktug Huseyin,Taskiran Dilek Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats. , 2019, ss.219 - 224.
AMA	DEĞİRMENCİ C,AFRASHİ F,erbas o,Aktug H,Taskiran D Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats. . 2019; 219 - 224.
Vancouver	DEĞİRMENCİ C,AFRASHİ F,erbas o,Aktug H,Taskiran D Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats. . 2019; 219 - 224.
IEEE	DEĞİRMENCİ C,AFRASHİ F,erbas o,Aktug H,Taskiran D "Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats." , ss.219 - 224, 2019.
ISNAD	DEĞİRMENCİ, Cumali vd. "Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats". (2019), 219-224.

APA	DEĞİRMENCİ C, AFRASHİ F, erbas o, Aktug H, Taskiran D (2019). Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats. Retina-Vitreus, 28(2), 219 - 224.
Chicago	DEĞİRMENCİ Cumali,AFRASHİ Filiz,erbas oytun,Aktug Huseyin,Taskiran Dilek Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats. Retina-Vitreus 28, no.2 (2019): 219 - 224.
MLA	DEĞİRMENCİ Cumali,AFRASHİ Filiz,erbas oytun,Aktug Huseyin,Taskiran Dilek Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats. Retina-Vitreus, vol.28, no.2, 2019, ss.219 - 224.
AMA	DEĞİRMENCİ C,AFRASHİ F,erbas o,Aktug H,Taskiran D Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats. Retina-Vitreus. 2019; 28(2): 219 - 224.
Vancouver	DEĞİRMENCİ C,AFRASHİ F,erbas o,Aktug H,Taskiran D Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats. Retina-Vitreus. 2019; 28(2): 219 - 224.
IEEE	DEĞİRMENCİ C,AFRASHİ F,erbas o,Aktug H,Taskiran D "Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats." Retina-Vitreus, 28, ss.219 - 224, 2019.
ISNAD	DEĞİRMENCİ, Cumali vd. "Therapeutic Effects of Edaravone on Retinopathy in Streptozotocin-Induced Diabetic Rats". Retina-Vitreus 28/2 (2019), 219-224.