Askorbik Asit ve Sodyum Selenitin Renal İskemi-Reperfüzyon Hasarında İnflamatuar Cevap ve Apoptoz Üzerine Etkileri

Yıl 2022, , 130 - 136, 01.03.2022

Songül Doğanay , Özcan Budak

https://doi.org/10.26453/otjhs.1056107

Öz

Amaç: Bu çalışmanın amacı, renal iskemi ve reperfüzyon (IR) hasarında askorbik asit (AA) ve sodyum selenit (SS) uygulamasının anti-inflamatuar ve anti-apoptotik etkilerini araştırmaktır.
Materyal ve Metot: Yirmi sekiz Wistar-albino sıçan dört gruba ayrıldı. Grup I; Kontrol grubu, Grup II; IR grubu, Grup III; IR+0,25mg/kg SS ve 100mg/kg AA ve Grup IV; IR+0,50mg/kg SS ve 200mg/kg AA. Kontrol grubuna sadece cerrahi stres oluşturuldu. IR grubunda, sağ nefrektomi yapıldıktan sonra sol böbrekte 60 dk iskemi ve 24 saat reperfüzyon sağlandı. Grup III ve Grup IV’e IR grubundaki işleme ek olarak IR işleminden 5 gün önce belirlenen dozlarda SS ve AA uygulandı.
Bulgular: Grup I, Grup III ve Grup IV ile karşılaştırıldığında Grup II‘de glomerulus ve renal tübüllerin morfolojik yapılarında şiddetli hasar oluştuğu görüldü (p<0,05). Grup I, Grup III ve Grup IV ile karşılaştırıldığında Grup II'de TNF-α, IL-6, Kaspaz-3 ve Bcl-2 ekspresyonu ve pozitif hücre yüzdesi istatistiksel olarak arttı (p<0,001).
Sonuç: Bu çalışma, askorbik asit ve sodyum selenit'in profilaktik olarak uygulanmasının akut böbrek hasarına karşı koruyucu etkiler gösterdiğini belirledi. 

Anahtar Kelimeler

Askorbik asit, inflamasyon, renal iskemi-reperfüzyon, sodyum selenit

Effects of Ascorbic Acid and Sodium Selenite on Inflammatory Response and Apoptosis in Renal Ischemia-Reperfusion Injury

Öz

Objective: The aim of this study is to investigate the anti-inflammatory and anti-apoptotic effects of ascorbic acid (AA) and sodium selenite (SS) administration in renal ischemia and reperfusion (IR) injury.
Materials and Methods: Twenty-eight Wistar-albino rats were divided into four groups. Group I; Control group, Group II; IR group, Group III; IR+0.25mg/kg SS and 100mg/kg AA and Group IV; IR+0.50mg/kg SS and 200mg/kg AA. In the control group, only surgical stress was created. In the IR group, 60 minutes of ischemia and 24 hours of reperfusion were applied in the left kidney after right nephrectomy. SS and AA were administered to Groups III and IV at doses determined 5 days before the IR procedure.
Results: In comparison of Group II with Group I, Group III and Group IV; severe damage was observed in the morphological structures of the glomerulus and renal tubules in Group II (p<0.05). Compared to Group I, Group III and Group IV the expression of TNF-α, IL-6, Caspase-3, and Bcl-2 and the percentage of positive cells increased statistically in Group II (p<0.001).
Conclusion: This study determined that prophylactic administration of ascorbic acid and sodium selenite showed protective effects against acute kidney injury. 

Anahtar Kelimeler

Ascorbic acid, inflammation, renal ischemia-reperfusion, sodium selenite

Kaynakça

• Cheng Z, Guo C. Pemafibrate pretreatment attenuates apoptosis and autophagy during hepatic ischemia-reperfusion injury by modulating jak2/stat3β/pparα pathway. PPAR Research. 2021;2021:1-15. doi:10.1155/2021/6632137
• Yamaguchi M, Okamoto K, Kusano T, et al. The effects of xanthine oxidoreductase inhibitors on oxidative stress markers following global brain ischemia reperfusion injury in C57BL/6 mice. PLoS One. 2015;10(7):e0133980. doi:10.1371/journal. pone.0133980
• Basile DP, Yoder MC. Renal endothelial dysfunction in acute kidney ischemia reperfusion injury. Cardiovascular & Haematological Disorders-Drug Targets. 2014; 14(1):3-14.
• Bhogal RH, Sutaria R, Afford SC. Hepatic liver ischemia/reperfusion injury: processes in inflammatory networks-a review. Liver Transpl. 2011;17:95. doi:10.1002/lt.22205
• Ma M, Ma ZH. Effect of tumor necrosis factor-alpha in rats with hepatic ischemia-reperfusion injury. Hepatobiliary&Pancreatic Diseases International. 2008;7:296-299.
• Dai J, Chen Q, Huang W, et al. Liver kinase B1 attenuates liver ischemia/reperfusion injury via inhibiting the NLRP3 inflammasome. Acta Biochimica et Biophysica Sinica. 2021;53:601-611.
• Kezić A, Stajic N, Thaiss F. Innate immune response in kidney ischemia/reperfusion injury: potential target for therapy. Journal of immunology research. 2017;2017:1-10. doi:10.1155/2017/6305439
• Pefanis A, Ierino FL, Murphy JM, Cowan PJ. Regulated necrosis in kidney ischemia-reperfusion injury. Kidney international. 2019;96:291-301. doi:10.1016/j.kint.2019.02.009
• Ahmadiasl N, Banaei S, Alihemmati A. Combination antioxidant effect of erythropoietin and melatonin on renal ischemia-reperfusion injury in rats. Iranian journal of basic medical sciences. 2013;16(12):1209-1216.
• Asgharpour M, Tolouian AC, Bhaskar LV, Tolouian R, Massoudi N. Herbal antioxidants and renal ischemic-reperfusion injury; an updated review. Journal of Nephropharmacology. 2020;10(1):e03. doi:10.34172/npj.2021.03
• Erkut B, Özyazicioğlu A, Karapolat BS, et al. Effects of ascorbic acid, alpha-tocopherol and allopurinol on ischemia-reperfusion injury in rabbit skeletal muscle: an experimental study. Drug Target Insights. 2007;2:DTI-S303. doi:10.4137/DTI.S303
• Sandhi J, Singh JP, Kaur T, Ghuman SS, Singh AP. Involvement of progesterone receptors in ascorbic acid–mediated protection against ischemia-reperfusion–induced acute kidney injury. Journal of Surgical Research. 2014;187:278-288. doi:10.1016/j.jss.2013.10.025
• Ahmadvand H, Babaeenezhad E, Nayeri H, Nezhad ZZ. Selenium effects on antioxidant and inflammatory indices in renal ischemia-reperfusion injury in rats. Journal of Renal Injury Prevention. 2019;8(2):71-77. doi:10.15171/jrip.2019.14
• Leskovec J, Levart A, Nemec Svete A, et al. Effects of supplementation with α-tocopherol, ascorbic acid, selenium, or their combination in linseed oil-enriched diets on the oxidative status in broilers. Poultry Science. 2018;97:1641-1650.
• Irmak MK, Koltuksuz U, Kutlu NO, et al. The effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in comparison with α-tocopherol in rat kidneys. Urological Research. 2001;29:190-193. doi:10.1007/s002400100185
• Zeng J, Tang ZH, Liu S, Guo SS. Clinicopathological significance of overexpression of interleukin-6 in colorectal cancer. World Journal of Gastroenterology. 2017;23(10):1780-1786. doi:10.3748/wjg.v23.i10.1780
• Pektaş A, Gemalmaz H, Balkaya M, et al. Renal iskemi/reperfüzyon hasarı oluşturulan ratlarda likopenin kısa dönemdeki koruyucu etkisi. Turkish Journal of Urology. 2014;40(1):46-51. doi:10.5152/tud.2014.53765
• Boozari M, Hosseinzadeh H. Natural medicines for acute renal failure: A review. Phytotherapy Research. 2017;31(12):1824-1835. doi:10.1002/ptr.5943
• Golab F, Kadkhodaee M, Zahmatkesh M, et al. Ischemic and non-ischemic acute kidney injury cause hepatic damage. Kidney International. 2009;75(8):783-792. doi:10.1038/ki.2008.683
• Liu L, Liu C, Hou L, et al. Protection against ischemia/reperfusion‑induced renal injury by co‑treatment with erythropoietin and sodium selenite. Molecular Medicine Reports. 2015;12(6):7933-7940. doi:10.3892/mmr.2015.4426
• Park SW, Ghim W, Oh S, et al. Association of vitreous vitamin C depletion with diabetic macular ischemia in proliferative diabetic retinopathy. PLoS One. 2019;14(6): e0218433. doi:10.1371/journal.pone.0218433
• Seo MY, Lee SM. Protective effect of low dose of ascorbic acid on hepatobiliary function in hepatic ischemia/reperfusion in rats. Journal of Hepatology. 2002;36(1):72-77. doi:10.1016/S0168-8278(01)00236-7
• Hasanvand A, Abbaszadeh A, Darabi S, Nazari A, Gholami M, Kharazmkia A. Evaluation of selenium on kidney function following ischemic injury in rats; protective effects and antioxidant activity. Journal of Renal Injury Prevention. 2017;6(2):93-98. doi:10.15171/jrip.2017.18
• Ostróżka-Cieślik A, Dolińska B, Ryszka F. Therapeutic potential of selenium as a component of preservation solutions for kidney transplantation. Molecules. 2020;25(16):3592. doi:10.3390/molecules25163592
• Aboutaleb N, Jamali H, Abolhasani M, Toroudi H. Lavender oil (Lavandula angustifolia) attenuates renal ischemia/reperfusion injury in rats through suppression of inflammation, oxidative stress and apoptosis. Biomedicine&Pharmacotherapy. 2019;110:9-19. doi:10.1016/j.biopha.2018.11.045
• Yaribeygi H, Farrokhi FR, Rezaee R, Sahebkar A. Oxidative stress induces renal failure: A review of possible molecular pathways. Journal of Cellular Biochemistry 2018;119(4):2990-2998. doi:10.1002/jcb.26450
• Kunak CS, Ugan RA, Cadirci E, et al. Nephroprotective potential of carnitine against glycerol and contrast-induced kidney injury in rats through modulation of oxidative stress, proinflammatory cytokines, and apoptosis. The British Journal of Radiology. 2016;89:105820140724. doi:10.1259/bjr.20140724
• Lakhani SA, Masud A, Kuida K, et al. Caspases 3 and 7: key mediators of mitochondrial events of apoptosis. Science. 2006;311(5762):847-851. doi:10.1126/science.1115035
• Jafari Anarkooli I, Sankian M, Ahmadpour S, Varasteh AR, Haghir H. Evaluation of Bcl-2 family gene expression and Caspase-3 activity in hippocampus STZ-induced diabetic rats. Experimental Diabetes Research. 2008;2008:1-6. doi:10.1155/2008/638467
• Yang B, Johnson TS, Thomas GL, et al. A shift in the Bax/Bcl-2 balance may activate caspase-3 and modulate apoptosis in experimental glomerulonephritis. Kidney International. 2002;62(4):1301-1313. doi:10.1111/j.1523-1755.2002.kid587.x