Evaluation of the protective role of antioxidants: α-tocopherol, vitamin C, and quercetin, against ibuprofen-induced renal damage in male Wistar rats
Keywords:Ibuprofen, Antioxidants, α-tocopherol, Vitamin C, Urea, Creatinine
Background: Ibuprofen, commonly used in management of pains and inflammatory conditions, has been associated with renal damage. The protective role of antioxidants against Ibuprofen-induced renal damage in wistar rats were investigated in this study.
Methods: The study was designed in two parts; first, to induce kidney damage and secondly, to determine protective role of antioxidants against ibuprofen-induced kidney injury. In the first phase, two groups of animals were used; one group treated with 120mg/kg ibuprofen daily for 14 days, while the other served as control and had distilled water. Serum malondialdehyde and kidney parameters were estimated after treatment and kidneys harvested for histology. In the protection study, animals were divided into five groups, with groups 1-4 having three sub-groups treated with 120mg/kg Ibuprofen and graded doses of vitamin E, vitamin C and quercetin respectively, while group five served as control. After 14days, antioxidant enzymes and kidney parameters were estimated, and the kidneys harvested for histology.
Results: Showed significant (p<0.05) increase in malondialdehyde, urea, creatinine, and uric-acid levels after ibuprofen administration. Conversely, there was significant (p<0.05) reduction in kidney parameters after co-administration of antioxidants with ibuprofen, with significant increase in antioxidant enzymes. Estimated antioxidant’s percentage protection showed vitamin E gave highest protection on the kidneys against ibuprofen-induced damage amongst others. Histology revealed atrophied glomeruli with widened capsular space, desquamated tubular epithelial cells and infiltrating lymphocytes after ibuprofen administration, but showed normal histo-architecture after co-administration with antioxidants.
Conclusion: Antioxidants such as α-tocopherol, vitamin C, quercetin, protected against ibuprofen-induced renal damage in Wistar rats.
Machado GC, Maher CG, Ferreira PH, Day RO, Pinheiro MB, Ferreira ML. Non-Steroidal inflammatory drugs for spinal pain: a systemic review and meta-analysis. Ann Rheumat Dis. 2017;76 (7): 1269-78.
Solomon DH, Husni ME, Libby PA. The risk of major nsaid toxicity with celecoxib, ibuprofen, or naproxen: a secondary analysis of the precision trial. Am J Med. 2017;130(12):1415-22.
Varrassa G, Pergolizzi JV, Dowling P, Paladini S, Hernaz D, Paladini A. Ibuprofen Safety at the Golden Anniversary: Are all NSAIDs the Same? A Narrative Review. Adv Ther. 2020;37:61-82.
Yeomans ND, Graham DY, Husni ME. Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the precision trial. Alim Pharmacol Therap. 2018; 47(11):1453-63.
Mahmood KS, Ahmed J, Jawad A. Non-steroidal anti-inflammatory drugs (NSAIDs), free Radicals and reactive oxygen species (ROS): A review of literature. Med J Basrah Uni. 2019;27(1):46-53.
Ahmad MH, Fatima M, Hossain M, Mondal AC. Evaluation of naproxen-induced oxidative stress, hepatotoxicity and in-vivo genotoxicity in male Wistar rats. J Pharm Anal. 2018;8(6):400-6.
Akbar A, Jelodar G, Nazifi S, Afsar T, Nasiri K. Oxidative stress as the underlying biomechanism of detrimental outcomes of ionizing and non-ionizing radiation on human health: antioxidant protective strategies. J Res Med Sci. 2019;21(4):e85655.
Galli F, Azzi A, Birringer M, Cook-Mills JM, Eggersdorfer M, Frank J. Vitamin E: Emerging aspects and new directions. J Free Rad Biol Med. 2017;102:16-36.
Liu D, Shi J, Ibarra AC, Kakuda Y. The scavenging capacity and synergistic effects of lycopene, vitamin E, vitamin C, and carotene mixtures on the DPPH free radical. J Food Sci Technol. 2018;41(7):1344-9.
Shao Q, Yin X, Lui H, Zhao B, Huang J, Li Z. Kidney injury following ibuprofen and acetaminophen: a real-world analysis of post-marketing surveillance data. Front Pharmacol. 2021;12:750108.
Nagy J, Kovács T. A brief review on the rising incidence of chronic kidney diseases and non-alcoholic fatty liver disease. Physiol Int J. 2019; 106(4):305-10.
Gomaa S. Adverse effects induced by diclofenac, ibuprofen, and paracetamol toxicity on immunological and biochemical parameters in Swiss albino mice. J Basic Applied Zool. 2018;79(5):72-92.
Bushra R, Aslam N. An overview of clinical pharmacology of Ibuprofen. Oman Medical J. 2010; 25(3):155-61.
Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. J Biochem Pharmacol. 2020;180:114-7.
Zoubek ME, Lucena MI, Andrade RJ, Stephens C. Systematic review: ibuprofen-induced liver injury. Aliment Pharmacol Therap. 2020;51:603-11.
Lefevre G, Bonneau C, Rahma S, Chanu B, Brault D, Couder R. Determination of plasma pro tein-bound malondialdehyde by derivative spectro-photometry. Eur J Clin Chem Clin Biochem. 1996;34(8):631-6.
Paoletti F, Aldinucci D, Mocali A, Caparrini A. A sensitive spectrophotometric method for the determination of superoxide dismutase activity in tissue extracts. Analyt Biochem.1986;154(2):536-41.
Tipple TE, Rogers LK. Methods for the determination of plasma or tissue glutathione levels. Methods Mol Biol. 2012;889:315-24.
Fawcett JK, Scott JE. A rapid and precise method for the determination of urea. J Clin Pathol. 1960;13(2): 156-9.
Joris RD, Marijn MS. Creatinine determination according to Jaffe what does it stand for? Nephrol Dial Transplant Plus. 2011;4(2):83-6.
Kayamori Y, Katayama Y, Matsuyama T, Urata T. Enzymatic method for assaying uric acid in serum with a new tetrazolium salt produces water-soluble formazan dye. Clin Biochem. 1997;30(8):595-9.
Titford M. Progress in the development of microscopical techniques for diagnostic pathology. J Histotechnol. 2009;32:9-19.
Gyurászová M, Gurecká R, Bábíčková J, Tóthová L. Oxidative stress in the pathophysiology of kidney disease: implications for monitoring and identification of biomarkers. Oxid Med Cell Long. 2020;20:547.
Duni A, Liakopoulos V, Roumeliotis S, Peschos D, Peschos S, Dounousi E. Oxidative stress in the pathogenesis and evolution of chronic kidney disease: untangling Ariadne's thread. Int J Mol Sci. 2019; 20(15):3711.
Lucas GNC, Leitão ACC, Alencar RL, Xavier RMF, Daher EDF, da Silva GB. Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs. Brasilian J Nephrol. 2019;41(1): 124-30.
Su L, Li Y, Xu R, Luo F, Gao Q, Chen R. Association of Ibuprofen Prescription with Acute kidney Injury Among Hospitalized Children in China. J Am Med Assoc. 2021;4(3):e210775.
Nagappen AS, Varghese J, Pranesh GT, Jeyaseelan V, Jacob M. Indomethacin and Ibuprofen inhibit activation of endothelial nitric oxide synthase in the rat kidney; Possible role of this effect in the pathogenesis of NSAIDs-induced renal damage. J Chem Biol Interact. 2014;221:77-87.
Zehiroglu C, Sarikaya SBO. The importance of antioxidants and place in today’s scientific and technological studies. J Food Sci Technol. 2019; 56(11):4757-74.
Wang Y, Quan F, Cao Q, Lin Y, Yue C, Cui X, et al. Quercetin alleviates acute kidney injury by inhibiting ferroptosis. J Adv Res. 2021;28:231-43.
Hong YA, Lim JH, Kim MY, Kim Y, Park HS, Kim HW, et al. Extracellular superoxide dismutase attenuates renal oxidative stress through the activation of adenosine monophosphate-activated protein kinase in diabetic nephropathy. Antioxidant Redox Sig. 2018;28:1543-61.
Marriott BP, Birt DF, Stallings VA, Yates AA. Vitamin C present knowledge in nutrition. 11th ed. London: Academic Press (Elsevier); 2020:155-70.
Dennis JM, Witting PK. Protective Role for Antioxidants in Acute Kidney Disease. Nutrients. 2017;9(7):718.
Xu D, Hu MJ, Wang YQ, Hu M, Cui YL. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules. 2019;24(6):1123.
Traber MG, Stevens JF. Vitamins C and E: Beneficial effects from a mechanistic perspective. Free Rad Biol Med. 2011;51(5):1000-13.
Borran M, Dashti-Khavidaki S, Alamdari A, Naderi N. Vitamin C and kidney transplantation: Nutritional status, potential efficacy, safety, and interactions. Clin Nutr. 2020;41:1-9.