Streptozotosin ile diyabet oluşturulan ratlarda alt ekstremite iskemi reperfüzyonuna karşı fullerenol C60’ın etkileri

Yıl 2020, Cilt: 4 Sayı: 6, 451 - 455, 01.06.2020

Hakan Kartal , Ayşegül Küçük , Aydan Kılıçarslan , Yücel Polat Nuran Süngü Gülay Kip Mustafa Arslan

https://doi.org/10.28982/josam.756665

Cited By: 2

Öz

Amaç: Suda çözünür bir fulleren olan Fullerenol C60'ın, serbest radikalleri in vitro ve in vivo temizleyebildiği gösterilmiştir. Çalışmanın amacı, fullerenol C60'ın iskemi reperfüzyon (I/R) sıçan modelinde alt iskelet kasları üzerindeki etkilerini araştırmaktı.
Yöntemler: Etik kurul onayı alındıktan sonra 30 Wistar Albino sıçan; 5 gruba ayrıldı (n: 6); Kontrol (C), diyabet (grup D), diyabet + fullerenol C60 grubu (DF), diyabet + I/R (grup DIR) ve diyabet I/R + fullerenol C60 (DIR-F). Diyabet için sıçanlara 55 mg / kg streptozotosin uygulandı. Diyabet oluşumundan dört hafta sonra sıçanlara 2 saatlik iskemi ve 2 saatlik reperfüzyon uygulandı. Reperfüzyon döneminin sonunda histopatolojik ve immünohistopatolojik incelemeler için tüm gruplardan alt ekstremite iskelet kası örnekleri alındı.
Bulgular: Miyozit ve endotelyal kaspaz 3 enzim aktiviteleri, özellikle DIR ve C, D, DF ve DIR-F grubunda yüksektir. Enflamasyon DIR grubunda C, DF ve DIR-F grubuna göre anlamlı olarak yüksektir (sırasıyla P<0,001, P=0,006, P<0,001). Myosit hasarı da DIR grubunda kontrol, C, DF ve DIR-F grubuna göre anlamlı derecede yüksektir (sırasıyla P<0,001, P=0,022, P<0,001). Vasküler dilatasyon ve konjesyon D, DF, DIR ve DIR-F grubunda kontrol grubuna göre anlamlı olarak yüksektir (P<0,001, tümü).
Sonuç: Sonuçlarımız, fullerenol C60'ın diyabetik sıçanlarda I/R'den kaynaklanan iskelet kası hasarına karşı koruyucu etkileri olduğunu doğrulamaktadır. Fullerenol C60'ın I/R hasarı üzerindeki etkilerini değerlendirmek için yapılacak gelecekteki çalışmalar, fullerenol C60'ın olası koruyucu etkilerini ve I/R hasarına bağlı doku hasarının altında yatan mekanizmaları anlamaya yardımcı olabilir.

Anahtar Kelimeler

İskemi reperfüzyon, Fullerenol C60, Kaspaz 3, Sıçan

Destekleyen Kurum

YOK

The effect of fullerenol C60 on skeletal muscle after lower limb ischemia reperfusion injury in streptozotocin-induced diabetic rats

Öz

Aim: Fullerenol, a water-soluble C60-fullerene, has been demonstrated to scavenge free radicals in vitro and in vivo. The aim of the study was to investigate the effects of fullerenol C60 on lower skeletal muscles in a rat model of ischemia/reperfusion (I/R).
Methods: After approval of the ethics committee, 30 Wistar Albino rat were divided into 5 groups with six animals per each as follows: Control (C), diabetes (D), diabetes+fullerenol C60 (DF), diabetes+I/R (group DIR) and diabetes I/R+fullerenol C60 (DIR-F) groups. Streptozotocin was administered to the rats to induce diabetes at a dose of 55 mg/kg. Four weeks after the onset of diabetes, rats were subjected to 2 hours of ischemia and 2 hours of reperfusion. At the end of the reperfusion period, skeletal muscle samples were taken from the lower extremity in all groups for histopathological and immunohistopathological examinations.
Results: Myositis and endothelial caspase 3 enzyme activities were high in all groups, particularly DIR. Compared to C, DF and DIR-F groups, inflammation and myositis were significantly higher in the DIR group (P=0.001, P=0.006, P=0.001, respectively, and P=0.001, P=0.022, P=0.001, respectively). Vascular dilatation and congestion were significantly more prominent in all groups compared to the control group (P=0.001 for all).
Conclusion: Our results confirm that fullerenol C60 has protective effects against skeletal muscle damage resulting from I/R in diabetic rats. Future studies conducted to evaluate these effects may help illuminate the action mechanism of fullerenol C60 and pathophysiology underlying the tissue damage related to I/R injury.

Anahtar Kelimeler

Ischemia reperfusion, Fullerenol C60, Caspase 3, Rat

Kaynakça

• 1. Suzuki S, Inaba K, Konno H. Ischemic preconditioning in hepatic ischemia and reperfusion. Curr Opin Organ Transplant. 2008 Apr;13(2):142-7. doi: 10.1097/MOT.0b013e3282f6a164. PMID: 18685294.
• 2. Montalvo-Jave EE, Escalante-Tattersfield T, Ortega-Salgado JA, Piña E, Geller DA. Factors in the pathophysiology of the liver ischemia-reperfusion injury. J Surg Res. 2008 Jun 1;147(1):153-9. doi: 10.1016/j.jss.2007.06.015. Epub 2007 Jul 27. PMID: 17707862; PMCID: PMC2443391.
• 3. Eltzschig HK, Collard CD. Vascular ischaemia and reperfusion injury. Br Med Bull. 2004 Oct 19;70:71-86. doi: 10.1093/bmb/ldh025. Erratum in: Br Med Bull. 2005;73-74:139. PMID: 15494470.
• 4. Gökşin İ, Akbulut M, Baltalarlı A, Saçar M, Kaya Ş, Özcan V, et al. The effect of normovolomic hemodilution on lung injury after ischemia-reperfusion of lower extremities. Turk Gogus Kalp Dama. 2006;14:54-8.
• 5. Cuzzocrea S, Riley DP, Caputi AP, Salvemini D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev. 2001 Mar;53(1):135-59. PMID: 11171943.
• 6. Amani H , Habibey R , Hajmiresmail SJ , Latifi S , Pazoki-Toroudi H , Akhavan O . Antioxidant nanomaterials in advanced diagnoses and treatments of ischemia reperfusion injuries. J Mater Chem B. 2017 Dec 28;5(48):9452-9476. doi: 10.1039/c7tb01689a. Epub 2017 Nov 24. PMID: 32264560.
• 7. Tong J, Zimmerman MC, Li S, Yi X, Luxenhofer R, Jordan R, et al. Neuronal uptake and intracellular superoxide scavenging of a fullerene (C60)-poly(2-oxazoline)s nanoformulation. Biomaterials. 2011 May;32(14):3654-65. doi: 10.1016/j.biomaterials.2011.01.068. Epub 2011 Feb 20. PMID: 21342705; PMCID: PMC3085347.
• 8. Wang IC, Tai LA, Lee DD, Kanakamma PP, Shen CK, Luh TY, et al. C(60) and water-soluble fullerene derivatives as antioxidants against radical-initiated lipid peroxidation. J Med Chem. 1999 Nov 4;42(22):4614-20. doi: 10.1021/jm990144s. PMID: 10579823.
• 9. Burlaka AP, Sidorik YP, Prylutska SV, Matyshevska OP, Golub OA, Prylutskyy YI, et al. Catalytic system of the reactive oxygen species on the C60 fullerene basis. Exp Oncol. 2004 Dec;26(4):326-7. PMID: 15627068.
• 10. Liu Q, Jin L, Shen FH, Balian G, Li XJ. Fullerol nanoparticles suppress inflammatory response and adipogenesis of vertebral bone marrow stromal cells--a potential novel treatment for intervertebral disc degeneration. Spine J. 2013 Nov;13(11):1571-80. doi: 10.1016/j.spinee.2013.04.004. Epub 2013 May 10. PMID: 23669123; PMCID: PMC3841235.
• 11. Liu Q, Jin L, Mahon BH, Chordia MD, Shen FH, Li X. Novel treatment of neuroinflammation against low back pain by soluble fullerol nanoparticles. Spine (Phila Pa 1976). 2013 Aug 1;38(17):1443-51. doi: 10.1097/BRS.0b013e31828fc6b7. PMID: 23466506; PMCID: PMC3731423.
• 12. YE S; Chen M, Jiang Y, Chen M, Zhou T, Wang Y. Polyhydroxylated fullerene attenuates oxidative stress-induced apoptosis via a fortifying Nrf2-regulated antioxidant defence system. Int J Nanomedicine. 2014; 9:2073-87.
• 13. Sayes CM., Fortner JD, Guo W, Lyon D, Boyd AM, Ausman KD, et al. The differential cytotoxicity of water-soluble fullerenes. Nano Letters. 2004; 4: 1881-7.
• 14. Prylutska SV, Matyshevska OP, Golub AA, Prylutskyy YI, Potebnya GP, Ritter U, et al. Study of С60 fullerenes and С 60-containing composites cytotoxicity in vitro. Mater Sci Eng C. 2007; 27: 1121-4.
• 15. Prylutska SV, Grynyuk II, Grebinyk SM, Matyshevska OP, Prylutskyy YuI, Ritter U, et al. Comparative study of biological action of fullerenes C60 and carbon nanotubes in thymus cells. Mat-wiss u Werkstofftech 2009; 40: 238-41.
• 16. Tolkachov M, Sokolova V, Loza K, Korolovych V, Prylutskyy Y, Epple M, et al. Study of biocompatibility effect of nanocarbon particles on various cell types in vitro. Mat-wiss u Werkstofftech 2016; 47: 216-21.
• 17. Eken H, Kurnaz E. (2019). Biochemical and histopathological evaluation of taxifolin: An experimental study in a rat model of liver ischemia reperfusion injury. J Surg Med. 2019;3(7): 494-7. DOI: 10.28982/josam.587598
• 18. Teoh NC, Farrell GC. Hepatic ischemia reperfusion injury: pathogenic mechanisms and basis for hepatoprotection. J Gastroenterol Hepatol. 2003 Aug;18(8):891-902. doi: 10.1046/j.1440-1746.2003.03056.x. PMID: 12859717.
• 19. Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000 Feb;190(3):255-66. doi: 10.1002/(SICI)1096-9896(200002)190:3<255::AID-PATH526>3.0.CO;2-6. PMID: 10685060.
• 20. Oyar EÖ, Kiriş I, Gülmen S, Ceyhan BM, Cüre MC, Delibaş N, et al. The protective effect of adrenomedullin on renal injury, in a model of abdominal aorta cross-clamping. Thorac Cardiovasc Surg. 2012 Feb;60(1):5-10. doi: 10.1055/s-0031-1293607. Epub 2012 Jan 5. PMID: 22222684.
• 21. Williams P, Lopez H, Britt D, Chan C, Ezrin A, Hottendorf R. Characterization of renal ischemia-reperfusion injury in rats. J Pharmacol Toxicol Methods. 1997 Feb;37(1):1-7. doi: 10.1016/s1056-8719(96)00141-4. PMID: 9086282.
• 22. Gu J, Sun P, Zhao H, Watts HR, Sanders RD, Terrando N, et al. Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice. Crit Care. 2011 Jun 24;15(3):R153. doi: 10.1186/cc10283. PMID: 21702944; PMCID: PMC3219027.
• 23. Yamamoto K, Wilson DR, Baumal R. Outer medullary circulatory defect in ischemic acute renal failure. Am J Pathol. 1984 Aug;116(2):253-61. PMID: 6465286; PMCID: PMC1900543.
• 24. Arendshorst WJ, Finn WF, Gottschalk CW. Pathogenesis of acute renal failure following temporary renal ischemia in the rat. Circ Res. 1975 Nov;37(5):558-68. doi: 10.1161/01.res.37.5.558. PMID: 1192555.
• 25. Katz MA. The expanding role of oxygen free radicals in clinical medicine. West J Med. 1986 Apr;144(4):441-6. PMID: 3521094; PMCID: PMC1306655.
• 26. Tüfek A, Tokgöz O, Aliosmanoglu I, Alabalik U, Evliyaoglu O, Çiftçi T, et al. The protective effects of dexmedetomidine on the liver and remote organs against hepatic ischemia reperfusion injury in rats. Int J Surg. 2013;11(1):96-100. doi: 10.1016/j.ijsu.2012.12.003. Epub 2012 Dec 20. PMID: 23261946.
• 27. Wang Y, Ji M, Chen L, Wu X, Wang L. Breviscapine reduces acute lung injury induced by left heart ischemic reperfusion in rats by inhibiting the expression of ICAM-1 and IL-18. Exp Ther Med. 2013 Nov;6(5):1322-1326. doi: 10.3892/etm.2013.1287. Epub 2013 Sep 4. PMID: 24223666; PMCID: PMC3820788.
• 28. Weiser MR, Williams JP, Moore FD Jr, Kobzik L, Ma M, Hechtman HB, et al. Reperfusion injury of ischemic skeletal muscle is mediated by natural antibody and complement. J Exp Med. 1996 May 1;183(5):2343-8. doi: 10.1084/jem.183.5.2343. PMID: 8642343; PMCID: PMC2192547.
• 29. Chan RK, Austen WG Jr, Ibrahim S, Ding GY, Verna N, Hechtman HB, et al. Reperfusion injury to skeletal muscle affects primarily type II muscle fibers. J Surg Res. 2004 Nov;122(1):54-60. doi: 10.1016/j.jss.2004.05.003. PMID: 15522315.
• 30. Andrade-Silva AR, Ramalho FS, Ramalho LN, Saavedra-Lopes M, Jordão AA Jr, Vanucchi H, et al. Effect of NFkappaB inhibition by CAPE on skeletal muscle ischemia-reperfusion injury. J Surg Res. 2009 May 15;153(2):254-62. doi: 10.1016/j.jss.2008.04.009. Epub 2008 May 7. PMID: 18755481.
• 31. Baumeister SP, Ofer N, Kleist C, Rebel M, Dohler B, Terness P, et al. Comparison of six methods for the assessment of ischemia-reperfusion injury in skeletal muscle following composite tissue allotransplantation. J Reconstr Microsurg. 2004 Apr;20(3):253-9. doi: 10.1055/s-2004-823113. PMID: 15088210.
• 32. McCormack MC, Kwon E, Eberlin KR, Randolph M, Friend DS, Thomas AC, et al. Development of reproducible histologic injury severity scores: skeletal muscle reperfusion injury. Surgery. 2008 Jan;143(1):126-33. doi: 10.1016/j.surg.2007.06.005. Epub 2007 Dec 3. PMID: 18154940.
• 33. Carmo-Araújo EM, Dal-Pai-Silva M, Dal-Pai V, Cecchini R, Anjos Ferreira AL. Ischaemia and reperfusion effects on skeletal muscle tissue: morphological and histochemical studies. Int J Exp Pathol. 2007 Jun;88(3):147-54. doi: 10.1111/j.1365-2613.2007.00526.x. PMID: 17504444; PMCID: PMC2517305.
• 34. Vignaud A, Hourde C, Medja F, Agbulut O, Butler-Browne G, Ferry A. Impaired skeletal muscle repair after ischemia-reperfusion injury in mice. J Biomed Biotechnol. 2010;2010:724914. doi: 10.1155/2010/724914. Epub 2010 May 9. PMID: 20467471; PMCID: PMC2866363.
• 35. Keskin D, Unlu RE, Orhan E, Erkilinç G, Bogdaycioglu N, Yilmaz FM. Effects of Remote Ischemic Conditioning Methods on Ischemia-Reperfusion Injury in Muscle Flaps: An Experimental Study in Rats. Arch Plast Surg. 2017 Sep;44(5):384-389. doi: 10.5999/aps.2017.44.5.384. Epub 2017 Sep 15. PMID: 28946719; PMCID: PMC5621827.
• 36. Lai YL, Murugan P, Hwang KC. Fullerene derivative attenuates ischemia-reperfusion-induced lung injury. Life Sci. 2003 Jan 31;72(11):1271-8. doi: 10.1016/s0024-3205(02)02374-3. PMID: 12570927.
• 37. Lai YL, Chiang LY. Water-soluble fullerene derivatives attenuate exsanguination-induced bronchoconstriction of guinea pigs. J Auton Pharmacol 1997; 17:229-3.
• 38. Pun PB, Lu J, Moochhala S. Involvement of ROS in BBB dysfunction. Free Radic Res. 2009 Apr;43(4):348-64. doi: 10.1080/10715760902751902. Epub 2009 Feb 24. PMID: 19241241.
• 39. Yin JJ, Lao F, Fu PP, Wamer WG, Zhao Y, Wang PC, Qiu Y, Sun B, Xing G, Dong J, Liang XJ, Chen C. The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials. Biomaterials. 2009 Feb;30(4):611-21. doi: 10.1016/j.biomaterials.2008.09.061. Epub 2008 Nov 4. PMID: 18986699.
• 40. Sarami Foroshani M, Sobhani ZS, Mohammadi MT, Aryafar M. Fullerenol nanoparticles decrease blood-brain barrier interruption and brain edema during cerebral ischemia-repurfusion injury probably by reduction of Interleukin-6 and matrix metalloproteinase-9 transcription. J Strok Cerebrovasc Dis. 2018;27:3053-65.
• 41. Zavodovskyi DO, Zay SY, Matvienko TY, Prylutskyy YI, Nurishchenko NY, Paradizova SS, et al. Influence of C(60) fullerene on the ischemia-reperfusion injury in the skeletal muscle of rat limb: mechanokinetic and biochemical analysis. Ukr Biochem J. 2018;90:70-81.
• 42. Erer D, Dursun AD, Oktar GL, Iriz E, Zor MH, Elmas C, et al. The effects of iloprost on lung injury induced by skeletal muscle ischemia-reperfusion. Bratisl Lek Listy. 2014;115(7):405-10. doi: 10.4149/bll_2014_080. PMID: 25077362.
• 43. Darabi S, Mohammadi MT. Fullerenol nanoparticles decrease ischaemia-induced brain injury and oedema through inhibition of oxidative damage and aquaporin-1 expression in ischaemic stroke. Brain Inj. 2017;31(8):1142-50. doi: 10.1080/02699052.2017.1300835. Epub 2017 May 16. PMID: 28506130.