Comparison of Effectiveness Ascorbic Acid and Magnesium on Renal Ischemia-Reperfusion Model in Rats

Year 2025, Volume: 9 Issue: 1, 10 - 22, 31.01.2025

Ural Can Ekmekçi , Deniz Özzeybek , Şule Özbilgin , Mücahit Özdemir , Tuğba Erkmen , Semra Koçtürk , Hatice Efsun Kolatan , Gökçen Bilici , Güven Erbil

Abstract

Project Number

2019.KB.SAG.019

Comparison of Effectiveness Ascorbic Acid and Magnesium on Renal Ischemia-Reperfusion Model in Rats

Abstract

ABSTRACT
Background: This study aims to determine the effectiveness of ascorbic acid and magnesium administration separately or combined before ischemia in the rat renal ischemia and reperfusion damage of the model.
Materials and methods: Thirty-five Wistar rats were randomized into five groups of seven animals each. Group1 only underwent laparotomy, followed for 285min until sacrification. Group2 45min ischemia; 240min reperfusions, no drugs were applied. Group 3 250mg/kg ascorbic acid was applied 60min before ischemia-reperfusion, Group4 200mg/kg magnesium sulfate was applied 60min before ischemia-reperfusion, Group5 both drugs were applied at the same doses 60min before ischemia-reperfusion. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the renal tissues received, serum blood urea nitrogen (BUN) and creatinine levels were measured in blood samples. H&E and PAS paintings for histological examinations. TUNEL immunohistochemical staining for apoptotic cell examinations.
Results: Oxidative stress parameter MDA value was found significantly lower in Group3 (p:0.034) and Group5 (p<0.001) compared to Group2. Endogen antioxidant parameter GSH value of Group 4 (p<0.001) and Group 5 (p<0,001) were significantly higher than the other groups. TUNEL counts of the Group5 was significantly lower than the countsGroup2 (p:0,005).
Conclusion: It was concluded that before ischemia, ascorbic acid and magnesium sulfate combination reduce the kidney damage in the rat renal IR model

Keywords

Kidney, Ischemia-Reperfusion Injury, Ascorbic Acid, Magnesium, Rat

Ethical Statement

This research was approved by Dokuz Eylul University Ethics Committee (no: 47/2018, decision date: 31.10.2018)

Supporting Institution

This work was supported by Dokuz Eylul University Scientific Research Coordinator (project number: 2019.KB.SAG.019).

Project Number

2019.KB.SAG.019

Thanks

None

References

• Collard CD, Gelman S. Prevention of Ischaemia –Reperfusion Injury. Anesthesiology 2001;94(6):1133-1138.
• Akan M, Ozbilgin S, Boztas N, et al. Effect of magnesium sulfate on renal ischemia-reperfusion
• Wever KE, Menting TP, Rovers M, et al. Ischaemic preconditioning in the animal kidney, a systematic review and meta-analysis. PLoS One 2012;7(2):1-10.
• Carden DL, Granger DN. Pathophysiology of ischemia–reperfusion injury. J Pathol 2000;190(3):255-266.
• Khajuria A, Tay C, Shi J, et al. Anesthetics attenuate ischemia-reperfusion induced renal injury: Effects and mechanisms. Acta Anaesthesiol Taiwanica 2014;52(4):176-184.
• Shokeir AA, Hussein AM, Awadalla A, et al. Protection against renal ischemia/reperfusion injury: A comparative experimental study of the effect of ischemic preconditioning vs. postconditioning. Arab J Urol 2012;10(4):418-424.
• Bagcik E, Ozkardesler S, Boztas N, et al. Effects of dexmedetomidine in conjunction with remote ischemic preconditioning on renal ischemia–reperfusion injury in rats. Brazilian J Anesthesiol (English Ed) 2014;64(6):382-390.
• Ergin B, Zuurbier CJ, Bezemer R, et al. Ascorbic acid improves renal microcirculatory oxygenation in a rat model of renal I/R injury. J Transl Intern Med 2016;3(3):116-125.
• Azari O, Kheirandish R, Azizi S, et al. Protective Effects of Hydrocortisone, Vitamin C and E Alone or in Combination against Renal İschaemia-Reperfusion Injury in Rat. Iran J Pathol 2015;10(4):272-280.
• Mohamed AEHA, Lasheen NN. Comparative study on the protective role of vitamin C and L-arginine in experimental renal ischemia reperfusion in adult rats. Int J Physiol Pathophysiol Pharmacol 2014;6(3):153-165.
• Oudemans-van Straaten HM, Spoelstra-de Man AME, de Waard MC. Vitamin C revisited. Crit Care 2014;18(4):1-13.
• Zhu Y Bin, Zhang YP, Zhang J, et al. Evaluation of Vitamin C supplementation on kidney function and vascular reactivity following renal ischemic injury in mice. Kidney Blood Press Res 2016;41(4):460-470.
• Korkmaz A, Kolankaya D. The protective effects of ascorbic acid against renal ischemia-reperfusion injury in male rats. Ren Fail 2009;31(1):36-43.
• Seo MY, Lee SM. Protective effect of low dose of ascorbic acid on hepatobiliary function in hepatic ischemia/reperfusion in rats. J Hepatol 2002;36(1):72-77.
• Pundir M, Arora S, Kaur T, et al. Effect of modulating the allosteric sites of N-methyl-D-aspartate receptors in ischemia-reperfusion induced acute kidney injury. J Surg Res 2013;183(2):668-677.
• Gröber U, Schmidt J, Kisters K. Magnesium in prevention and therapy. Nutrients 2015;7(9):8199-8226.
• Kavak EC, Bulmus FG, Bulmus O, et al. Magnesium: Does it reduce ischemia/reperfusion injury in an adnexal torsion rat model? Drug Des Devel Ther 2018;12:409-415.
• Kao MC, Jan WC, Tsai PS, et al. Magnesium sulfate mitigates lung injury induced by bilateral lower limb ischemia-reperfusion in rats. J Surg Res 2011;171(1):e97-e106.
• Marques dos Santos CH, Dourado DM, Kato da Silva BA, et al. Atorvastatin Protects Kidney from Remote Reperfusion Injury. Ann Vasc Surg 2018.
• Wietzikoski EGG, Foiatto JC, Czeczko NG, et al. Tadalafil protector effect during ischemia-reperfusion in rats. Acta Cir Bras 2017.
• Tsutsui H, Shimokawa T, Miura T, et al. Effect of monoamine oxidase inhibitors on ischemia/reperfusion-induced acute kidney injury in rats. Eur J Pharmacol 2018;818:38-42.
• Si Y, Bao H, Han L, et al. Dexmedetomidine protects against renal ischemia and reperfusion injury by inhibiting the JAK/STAT signaling activation. J Transl Med 2013.
• Özlülerden Y, Toktaş C, Aybek H, et al. The renoprotective effects of mannitol and udenafil in renal ischemia-reperfusion injury model. Investig Clin Urol 2017.
• Orvieto MA, Zorn KC, Mendiola F, et al. Recovery of Renal Function After Complete Renal Hilar Versus Artery Alone Clamping During Open and Laparoscopic Surgery. J Urol 2007;177(6):2371-2374.
• Simmons MN, Schreiber MJ, Gill IS. Surgical Renal İschaemia: A Contemporary Overview. J Urol 2008;180(1):19-30.
• Kocoglu H, Ozturk H, Ozturk H, et al. Effect of dexmedetomidine on ischemia-reperfusion injury in rat kidney: A histopathologic study. Ren Fail 2009;31(1):70-74.
• Fouad AA, Al-Mulhim AS, Jresat I, Morsy MA. Protective effects of captopril in diabetic rats exposed to ischemia/reperfusion renal injury. J Pharm Pharmacol 2013;65(2):243-252.
• Williams P, Lopez H, Britt D, et al. Characterization of Renal Ischaemia-Reperfusion Injury in Rats. J Pharmacol Toxicol Methods 1997;Feb:37(1):1-7.
• Singbartl K, Ley K. Protection from Ischaemia-Reperfusion Induced Severe Acute Renal Failure by Blocking E-Selectin. Crit Care Med 2000:28;2507-2514
• Hammad FT, Ojha S, Azimullah S, et al. Does β-Caryophyllene Protect against Renal Dysfunction Following İschaemia-Reperfusion Injury in the Rat? Int J Physiol Pathophysiol Pharmacol 2018;10(6):163–171.
• Yang S, Chou WP, Pei L. Effects of propofol on renal ischemia/reperfusion injury in rats. Exp Ther Med 2013;6(5):1177-1183.
• Li YW, Zhang Y, Zhang L, et al. Protective effect of tea polyphenols on renal ischemia/reperfusion injury via suppressing the activation of TLR4/NF-κB p65 signal pathway. Gene 2014;542(1):46-51.
• Yamaki VN, Goncalves TB, Coelho JV. et al.Protective effect of remote ischemic per-conditioning in the ischemia and reperfusion-induce renal injury in rats. Rev Col Bras Cir 2012;39:529-533.
• Yılmaz Selçuk N, Yakan B, San A, et al. Deneysel sıcak renal iskemi ve reperfüzyonda lipid peroksidasyonu ve alpha-tocopherol tedavisinin değerlendirilmesi. Türk Nefroloji Diyaliz ve Transplantasyon Dergisi Vol 1.; 1996.
• Luo LN, Xie DQ, Zhang XG, et al. Osthole decreases renal ischemia-reperfusion injury by suppressing JAK2/STAT3 signaling activation. Exp Ther Med 2016;12(4):2009-2014.
• Zhang J, Tang L, Li G Sen, Wang J. The anti-inflammatory effects of curcumin on renal ischemia-reperfusion injury in rats. Ren Fail 2018;40(1):680-686.
• Cochrane J, Williams BT, Banerjee A, et al. Ischaemic preconditioning attenuates functional, metabolic, and morphologic injury from ischemic acute renal failure in the rat. Ren Fail 1999;21(2):135-145.
• JI Xiang, MA Lu-Lin, LU Jian. Expression of kidney injury molecule-1 in renal ischemic postconditioning and its protective effect against renal ischemia-reperfusion injury in rats. J Peking Univ 2012;44:511-517.
• Zhao Z, Tang Z, Zhang W, et al. Magnesium isoglycyrrhizinate protects against renal-ischemia-reperfusion injury in a rat model via anti-inflammation, anti-oxidation and anti-apoptosis. Mol Med Rep 2017;16(3):3627-3633.
• Kozin S, Kravtsov A, Ivashchenko L, et al. Study of the Magnesium Comenate Structure, Its Neuroprotective and Stress-Protective Activity. Int J Mol Sci 2023;24(9):8046.
• Chen S da, Chen Y bin, Peng Y, et al. Role of PI3K/Akt signaling in the protective effect of magnesium sulfate against ischemia-perfusion injury of small intestine in rats. Chin Med J (Engl) 2010;123(11):1447-1452.
• Kressel M, Groscurth P. Distinction of apoptotic and necrotic cell death by in situ labelling of fragmented DNA. Cell Tissue Res 1994;278(3):549-556.
• Chang YK, Choi H, Jeong JY, et al. Dapagliflozin, SGLT2 Inhibitor, Attenuates renal ischemia-reperfusion injury. PLoS One 2016;11(7):1-14.
• Yang K, Li WF, Yu JF, et al. Diosmetin protects against ischemia/reperfusion-induced acute kidney injury in mice. J Surg Res 2017;214(86717):69-78.
• Herrera K, Cahoon RE, Kumaran S, Jez JM. Reaction mechanism of glutathione synthetase from Arabidopsis thaliana: Site-directed mutagenesis of active site residues. J Biol Chem 2007;282(23):17157-17165.