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The effects of riboflavin on ischemia/reperfusion induced renal injury: Role on caspase-3 expression

Yıl 2019, Cilt: 23 Sayı: 3, 379 - 386, 27.06.2025

Betül Ayaz Adakul Büşra Ertaş , Zatiye Ayça Çevikelli Dilek Özbeyli , Feriha Ercan Cansu Kandemir , Ozge Cevik , Tarık Şener , Göksel Şener

Öz

Reactive oxygen metabolites play important roles in ischemia/reperfusion (I/R) injury in several organ systems. Riboflavin has been shown to exert antioxidant and/or anti-inflammatory activities in several experimental models. The aim of this study was to investigate the role of riboflavin against I/R injury in the rat kidney. Wistar albino rats 200-300 g weighing were divided into 3 groups. One week after unilateral nephrectomy, the IR procedure was applied to the rats. To induce I/R injury renal pedicle was clamped for 45 minutes and then rats were allowed reperfusion for 6 hours. Riboflavin (25 mg/kg, orally) or vehicle was administered for one week as pretreatment. After decapitation, kidney tissue samples were taken for the evaluation of malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and 8-hydroxydeoxyguanosine (8-OHdG), a specific marker of oxidative DNA damage. Furthermore, myeloperoxidase (MPO) and caspase-3 activities were also examined together with histological analysis. Ischemia/reperfusion induced significant increases in MDA and 8-OHdG levels and MPO and caspase- 3 activities, and decrese in GSH levels. In the riboflavin treatment these indices were found to be reversed back to control levels. The present data demonstrated that riboflavin, through its antioxidant effect, attenuates I/R induced acute renal injury in rats.

Anahtar Kelimeler

Antioxidants ischemia reperfusion riboflavin caspase

Kaynakça

  • [1] Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011; 17: 1391-401. [CrossRef]
  • [2] Şener G, Sehirli AO, Keyer-Uysal M, Arbak S, Ersoy Y, Yegen BC. The protective effect of melatonin on renal ischemia-reperfusion injury in the rat. J Pineal Res. 2002; 32: 120-6. [CrossRef]
  • [3] Parks DA, Bulkley GB, Granger DA, Hamilton SR, Mccord JM. Ischemic injury in the cat small intestine: Role of superoxide radicals. Gastroenterology. 1982; 82: 9-15.
  • [4] Sutton TA. Alteration of microvascular permeability in acute kidney injury. Microvasc Res. 2009; 77: 4-7. [CrossRef]
  • [5] Kettle AJ, Winterbourn CC. Myeloperoxidase: A key regulator of neutrophil oxidant production. Redox Rep. 1997; 3: 3-15. [CrossRef]
  • [6] Singh D, Kaur R, Chander V, Chopra K. Antioxidants in the prevention of renal disease. J Med Food. 2006; 9: 443-50. [CrossRef]
  • [7] Powers HJ. Riboflavin (vitamin B-2) and health. Am J Clin Nutr. 2003; 77: 1352-1360. [CrossRef]
  • [8] Ashoori M, Saedisomeolia A. Riboflavin (vitamin B2) and oxidative stress: A review. Br J Nutr. 2014; 111: 1985-1991. [CrossRef]
  • [9] Sanches SC, Ramalho LN, Mendes-Braz M, Terra VA, Cecchini R, Augusto MJ, Ramalho FS. Riboflavin (vitamin B-2) reduces hepatocellular injury following liver ischaemia and reperfusion in mice. Food Chem Toxicol. 2014; 67: 65–71. [CrossRef]
  • [10] Betz AL, Ren XD, Ennis SR, Hultquist DE. Riboflavin reduces edema in focal cerebral ischemia. Acta Neurochir Suppl (Wien). 1994; 60: 314-317. [CrossRef]
  • [11] Seekamp A, Hultquist DE, Till GO. Protection by vitamin B2 against oxidant-mediated acute lung injury. Inflammation. 1999; 23: 449-460. [CrossRef]
  • [12] Kotegawa M, Sugiyama M, Haramaki N. Protective effects of riboflavin and its derivatives against ischemic reperfused damage of rat heart. Biochem Mol Biol Int. 1994; 34: 685-691.
  • [13] García JJ, Reiter RJ, Guerrero JM, Escames G, Yu BP, Oh CS, Muñoz-Hoyos A. Melatonin prevents changes in microsomal membrane fluidity during induced lipid peroxidation. FEBS Lett. 1997; 408: 297-300. [CrossRef]
  • [14] Sehirli AO, Sener G, Satıroglu H, Ayanoglu-Dulger G. Protective effect of N-acetylcysteine on the renal ischemia/reperfusion injury in the rat. J Nephrol. 2003; 16: 75–80.
  • [15] Aragno M, Cutrin JC, Mastrocola R, Perrelli MG, Restivo F, Poli G, Danni O, Boccuzzi G. Oxidative stress and kidney dysfunction due to ischemia/reperfusion in rat: attenuation by dehydroepiandrosterone. Kidney Int. 2003; 64: 836-843. [CrossRef]
  • [16] Al-Harbi NO, Imam F, Nadeem A, Al-Harbi MM, Iqbal M, Ahmad SF. Carbon tetrachloride-induced hepatotoxicity in rat is reversed by treatment with riboflavin. Int Immunopharmacol. 2014; 21: 383-388. [CrossRef]
  • [17] Franca CF, Vianna LM. Effectiveness of B vitamins on the control of hypertension and stroke events of SHRSP rats. J Diet Suppl. 2010; 7: 71-77. [CrossRef]
  • [18] Al-Harbi NO, Imam F, Nadeem A, Al-Harbi MM, Korashy HM, Sayed-Ahmed MM, Hafez MM, Al-Shabanah OA, Nagi MN, Bahashwan S. Riboflavin attenuates lipopolysaccharide-induced lung injury in rats. Toxicol Mech Methods. 2015; 25: 417-423. [CrossRef]
  • [19] Szabo S, Nagy L, Plebani M. Glutathione, protein sulfhydryls and cysteine proteases in gastric mucosal injury and protection. Clin Chim Acta. 1992; 206: 95-105. [CrossRef]
  • [20] Zimmerman BJ, Grsham MB, Granger DN. Role of oxidants in ischemia/reperfusion induced granulocyte infiltration. Am J Physiol. 1990; 258: G185-190. [CrossRef]
  • [21] Karakoyun B, Ertaş B, Yüksel M, Akakın D, Çevik Ö, Şener G. Ameliorative effects of riboflavin on acetic acid induced colonic injury in rats. Clin Exp Pharmacol Physiol. 2018; 45: 563-572. [CrossRef]
  • [22] Tekin G, İsbir S, Şener G, Çevik Ö, Çetinel Ş, Dericioğlu O, Arsan S, Çobanoğlu A. The preventive and curative effects of melatonin against abdominal aortic aneurysm in rats. J Vasc Surg. 2018; 67: 1546-1555. [CrossRef]
  • [23] Grunenfelder J, Miniati DN, Murata S, Falk V, Hoyt EG, Kown M, Koransky ML, Robbins RC. Upregulation of Bcl-2 through caspase-3 inhibition ameliorates ischemia/reperfusion injury in rat cardiac allografts. Circulation. 2001; 104: I202-206.
  • [24] Sener TE, Tavukcu HH, Atasoy BM, Cevik O, Kaya OT, Cetinel S, Dagli Degerli A, Tinay I, Simsek F, Akbal C, Butticè S, Sener G. Resveratrol treatment may preserve the erectile function after radiotherapy by restoring antioxidant defence mechanisms, SIRT1 and NOS protein expressions. Int J Impot Res. 2018; 30: 179-188. [CrossRef]
  • [25] Sener G, Sehirli O, Velioglu Ogunc A, Cetinel S, Gedik N, Caner M, Sakarcan A, Yeğen BC. Montelukast protects against renal ischemia/reperfusion injury in rats. Pharmacol Res. 2006; 54: 65–71. [CrossRef]
  • [26] Yu Z, Morimoto K, Yu J, Bao W, Okita Y, Okada K. Endogenous superoxide dismutase activation by oral administration of riboflavin reduces abdominal aortic aneurysm formation in rats. J Vasc Surg. 2016; 64: 737-745. [CrossRef]
  • [27] Beuge JA, Aust SD. Microsomal lipid peroxidation. Meth Enzymol. 1978; 52: 302-311. [CrossRef]
  • [28] Beutler E. Glutathione in red blood cell metabolism. A Manuel of Biochemical Methods. Grune & Stratton, New York, 1975; pp. 112-114.
  • [29] Hillegass LM, Griswold DE, Brickson B, Albrightson-Winslow C. Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods. 1990; 24: 285-295. [CrossRef]
  • [30] Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72: 248–254. [CrossRef]

Yıl 2019, Cilt: 23 Sayı: 3, 379 - 386, 27.06.2025

Betül Ayaz Adakul Büşra Ertaş , Zatiye Ayça Çevikelli Dilek Özbeyli , Feriha Ercan Cansu Kandemir , Ozge Cevik , Tarık Şener , Göksel Şener

Öz

Kaynakça

  • [1] Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011; 17: 1391-401. [CrossRef]
  • [2] Şener G, Sehirli AO, Keyer-Uysal M, Arbak S, Ersoy Y, Yegen BC. The protective effect of melatonin on renal ischemia-reperfusion injury in the rat. J Pineal Res. 2002; 32: 120-6. [CrossRef]
  • [3] Parks DA, Bulkley GB, Granger DA, Hamilton SR, Mccord JM. Ischemic injury in the cat small intestine: Role of superoxide radicals. Gastroenterology. 1982; 82: 9-15.
  • [4] Sutton TA. Alteration of microvascular permeability in acute kidney injury. Microvasc Res. 2009; 77: 4-7. [CrossRef]
  • [5] Kettle AJ, Winterbourn CC. Myeloperoxidase: A key regulator of neutrophil oxidant production. Redox Rep. 1997; 3: 3-15. [CrossRef]
  • [6] Singh D, Kaur R, Chander V, Chopra K. Antioxidants in the prevention of renal disease. J Med Food. 2006; 9: 443-50. [CrossRef]
  • [7] Powers HJ. Riboflavin (vitamin B-2) and health. Am J Clin Nutr. 2003; 77: 1352-1360. [CrossRef]
  • [8] Ashoori M, Saedisomeolia A. Riboflavin (vitamin B2) and oxidative stress: A review. Br J Nutr. 2014; 111: 1985-1991. [CrossRef]
  • [9] Sanches SC, Ramalho LN, Mendes-Braz M, Terra VA, Cecchini R, Augusto MJ, Ramalho FS. Riboflavin (vitamin B-2) reduces hepatocellular injury following liver ischaemia and reperfusion in mice. Food Chem Toxicol. 2014; 67: 65–71. [CrossRef]
  • [10] Betz AL, Ren XD, Ennis SR, Hultquist DE. Riboflavin reduces edema in focal cerebral ischemia. Acta Neurochir Suppl (Wien). 1994; 60: 314-317. [CrossRef]
  • [11] Seekamp A, Hultquist DE, Till GO. Protection by vitamin B2 against oxidant-mediated acute lung injury. Inflammation. 1999; 23: 449-460. [CrossRef]
  • [12] Kotegawa M, Sugiyama M, Haramaki N. Protective effects of riboflavin and its derivatives against ischemic reperfused damage of rat heart. Biochem Mol Biol Int. 1994; 34: 685-691.
  • [13] García JJ, Reiter RJ, Guerrero JM, Escames G, Yu BP, Oh CS, Muñoz-Hoyos A. Melatonin prevents changes in microsomal membrane fluidity during induced lipid peroxidation. FEBS Lett. 1997; 408: 297-300. [CrossRef]
  • [14] Sehirli AO, Sener G, Satıroglu H, Ayanoglu-Dulger G. Protective effect of N-acetylcysteine on the renal ischemia/reperfusion injury in the rat. J Nephrol. 2003; 16: 75–80.
  • [15] Aragno M, Cutrin JC, Mastrocola R, Perrelli MG, Restivo F, Poli G, Danni O, Boccuzzi G. Oxidative stress and kidney dysfunction due to ischemia/reperfusion in rat: attenuation by dehydroepiandrosterone. Kidney Int. 2003; 64: 836-843. [CrossRef]
  • [16] Al-Harbi NO, Imam F, Nadeem A, Al-Harbi MM, Iqbal M, Ahmad SF. Carbon tetrachloride-induced hepatotoxicity in rat is reversed by treatment with riboflavin. Int Immunopharmacol. 2014; 21: 383-388. [CrossRef]
  • [17] Franca CF, Vianna LM. Effectiveness of B vitamins on the control of hypertension and stroke events of SHRSP rats. J Diet Suppl. 2010; 7: 71-77. [CrossRef]
  • [18] Al-Harbi NO, Imam F, Nadeem A, Al-Harbi MM, Korashy HM, Sayed-Ahmed MM, Hafez MM, Al-Shabanah OA, Nagi MN, Bahashwan S. Riboflavin attenuates lipopolysaccharide-induced lung injury in rats. Toxicol Mech Methods. 2015; 25: 417-423. [CrossRef]
  • [19] Szabo S, Nagy L, Plebani M. Glutathione, protein sulfhydryls and cysteine proteases in gastric mucosal injury and protection. Clin Chim Acta. 1992; 206: 95-105. [CrossRef]
  • [20] Zimmerman BJ, Grsham MB, Granger DN. Role of oxidants in ischemia/reperfusion induced granulocyte infiltration. Am J Physiol. 1990; 258: G185-190. [CrossRef]
  • [21] Karakoyun B, Ertaş B, Yüksel M, Akakın D, Çevik Ö, Şener G. Ameliorative effects of riboflavin on acetic acid induced colonic injury in rats. Clin Exp Pharmacol Physiol. 2018; 45: 563-572. [CrossRef]
  • [22] Tekin G, İsbir S, Şener G, Çevik Ö, Çetinel Ş, Dericioğlu O, Arsan S, Çobanoğlu A. The preventive and curative effects of melatonin against abdominal aortic aneurysm in rats. J Vasc Surg. 2018; 67: 1546-1555. [CrossRef]
  • [23] Grunenfelder J, Miniati DN, Murata S, Falk V, Hoyt EG, Kown M, Koransky ML, Robbins RC. Upregulation of Bcl-2 through caspase-3 inhibition ameliorates ischemia/reperfusion injury in rat cardiac allografts. Circulation. 2001; 104: I202-206.
  • [24] Sener TE, Tavukcu HH, Atasoy BM, Cevik O, Kaya OT, Cetinel S, Dagli Degerli A, Tinay I, Simsek F, Akbal C, Butticè S, Sener G. Resveratrol treatment may preserve the erectile function after radiotherapy by restoring antioxidant defence mechanisms, SIRT1 and NOS protein expressions. Int J Impot Res. 2018; 30: 179-188. [CrossRef]
  • [25] Sener G, Sehirli O, Velioglu Ogunc A, Cetinel S, Gedik N, Caner M, Sakarcan A, Yeğen BC. Montelukast protects against renal ischemia/reperfusion injury in rats. Pharmacol Res. 2006; 54: 65–71. [CrossRef]
  • [26] Yu Z, Morimoto K, Yu J, Bao W, Okita Y, Okada K. Endogenous superoxide dismutase activation by oral administration of riboflavin reduces abdominal aortic aneurysm formation in rats. J Vasc Surg. 2016; 64: 737-745. [CrossRef]
  • [27] Beuge JA, Aust SD. Microsomal lipid peroxidation. Meth Enzymol. 1978; 52: 302-311. [CrossRef]
  • [28] Beutler E. Glutathione in red blood cell metabolism. A Manuel of Biochemical Methods. Grune & Stratton, New York, 1975; pp. 112-114.
  • [29] Hillegass LM, Griswold DE, Brickson B, Albrightson-Winslow C. Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods. 1990; 24: 285-295. [CrossRef]
  • [30] Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72: 248–254. [CrossRef]
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Temel Farmakoloji
Bölüm Articles
Yazarlar

Betül Ayaz Adakul

Büşra Ertaş

Zatiye Ayça Çevikelli

Dilek Özbeyli

Feriha Ercan

Cansu Kandemir

Ozge Cevik

Tarık Şener

Göksel Şener

Yayımlanma Tarihi 27 Haziran 2025
Yayımlandığı Sayı Yıl 2019 Cilt: 23 Sayı: 3

Kaynak Göster

APA Ayaz Adakul, B., Ertaş, B., Çevikelli, Z. A., Özbeyli, D., vd. (2025). The effects of riboflavin on ischemia/reperfusion induced renal injury: Role on caspase-3 expression. Journal of Research in Pharmacy, 23(3), 379-386.
AMA Ayaz Adakul B, Ertaş B, Çevikelli ZA, Özbeyli D, Ercan F, Kandemir C, Cevik O, Şener T, Şener G. The effects of riboflavin on ischemia/reperfusion induced renal injury: Role on caspase-3 expression. J. Res. Pharm. Haziran 2025;23(3):379-386.
Chicago Ayaz Adakul, Betül, Büşra Ertaş, Zatiye Ayça Çevikelli, Dilek Özbeyli, Feriha Ercan, Cansu Kandemir, Ozge Cevik, Tarık Şener, ve Göksel Şener. “The Effects of Riboflavin on ischemia/Reperfusion Induced Renal Injury: Role on Caspase-3 Expression”. Journal of Research in Pharmacy 23, sy. 3 (Haziran 2025): 379-86.
EndNote Ayaz Adakul B, Ertaş B, Çevikelli ZA, Özbeyli D, Ercan F, Kandemir C, Cevik O, Şener T, Şener G (01 Haziran 2025) The effects of riboflavin on ischemia/reperfusion induced renal injury: Role on caspase-3 expression. Journal of Research in Pharmacy 23 3 379–386.
IEEE B. Ayaz Adakul, B. Ertaş, Z. A. Çevikelli, D. Özbeyli, F. Ercan, C. Kandemir, O. Cevik, T. Şener, ve G. Şener, “The effects of riboflavin on ischemia/reperfusion induced renal injury: Role on caspase-3 expression”, J. Res. Pharm., c. 23, sy. 3, ss. 379–386, 2025.
ISNAD Ayaz Adakul, Betül vd. “The Effects of Riboflavin on ischemia/Reperfusion Induced Renal Injury: Role on Caspase-3 Expression”. Journal of Research in Pharmacy 23/3 (Haziran 2025), 379-386.
JAMA Ayaz Adakul B, Ertaş B, Çevikelli ZA, Özbeyli D, Ercan F, Kandemir C, Cevik O, Şener T, Şener G. The effects of riboflavin on ischemia/reperfusion induced renal injury: Role on caspase-3 expression. J. Res. Pharm. 2025;23:379–386.
MLA Ayaz Adakul, Betül vd. “The Effects of Riboflavin on ischemia/Reperfusion Induced Renal Injury: Role on Caspase-3 Expression”. Journal of Research in Pharmacy, c. 23, sy. 3, 2025, ss. 379-86.
Vancouver Ayaz Adakul B, Ertaş B, Çevikelli ZA, Özbeyli D, Ercan F, Kandemir C, Cevik O, Şener T, Şener G. The effects of riboflavin on ischemia/reperfusion induced renal injury: Role on caspase-3 expression. J. Res. Pharm. 2025;23(3):379-86.