Celecoxib has Preventive and Therapeutic Benefits against Nephrotoxicity Caused by Gentamicin in Mice

Abstract

It’s crucial to comprehend the impact of oxidative stress and pro-inflammatory cytokines in the gentamicin-induced kidney injury mechanism. Celecoxib was administered orally either before or after intraperitoneal therapy with gentamicin in mice. The serum levels of creatinine (SCr), blood urea nitrogen (BUN), IL-6, and TNF-α were measured by ELISA test, as well as the levels of the kidney tissue malondialdehyde (MDA), and glutathione (GSH) were also estimated spectrophotometrically. The renal expression of nuclear factor-κB (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase 2 (COX-2) mRNAs were evaluated by qPCR. Histopathological evaluation and Immunohistochemical examination of kidney NF-κB, IL-6, and COX-2 were also, performed. Celecoxib successfully prevented gentamicin-induced kidney damage as indicated by reducing blood BUN, SCr, and tissue MDA levels and increasing renal tissue GSH levels as well as lowering the blood IL-6 and TNF-α in comparison to mice received gentamicin. Furthermore, celecoxib has inhibited COX-2, NF-κB, IL-6, and TNF-α expression in the renal tissue. It is noteworthy that celecoxib therapy after gentamicin administration brought about substantially the same results as celecoxib treatment before gentamicin injection in mice. Our results showed the role of celecoxib as a therapeutic tool for gentamicin-induced nephrotoxicity as well as raised its beneficial prophylactic role in this medical challenge by attenuating oxidative stress and inflammation.

Keywords

Celecoxib - Gentamicin - Nephrotoxicity - Oxidative stress - Inflammatory markers - Mice.

Publication History

Received: 21 January 2022

Accepted: 28 February 2022

Article published online:
31 March 2022

• References

• 1 Ahmed S, Gul S, Gul H, Zia-Ul-Haq M, Ercisli S. Cyclooxygenase-2 inhibition improves antioxidative defense during experimental hypercholesterolemia. Bosn J Basic Med Sci 2014; 14: 63-69
• 2 Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int 2011; 79: 33-45
• 3 Corona PS, Espinal L, Rodríguez-Pardo D, Pigrau C, Larrosa N, Flores X. Antibiotic susceptibility in gram-positive chronic joint arthroplasty infections: increased aminoglycoside resistance rate in patients with prior aminoglycoside-impregnated cement spacer use. J Arthroplasty 2014; 29: 1617-1621
• 4 Leis JA, Rutka JA, Gold WL. Aminoglycoside-induced ototoxicity. CMAJ. 2015; 187: E52
• 5 Fisel P, Renner O, Nies AT, Schwab M, Schaeffeler E. Solute carrier transporter and drug-related nephrotoxicity: the impact of proximal tubule cell models for preclinical research. Expert Opin Drug MetabToxicol 2014; 10: 395-408
• 6 Quiros Y, Vicente-Vicente L, Morales AI, López-Novoa JM, López-Hernández FJ. An integrative overview on the mechanisms underlying the renal tubular cytotoxicity of gentamicin. Toxicol Sci 2011; 119: 245-256
• 7 Zhu X, Jiang X, Li A, Zhao Z, Li S. S-Allylmercaptocysteine Attenuates Cisplatin-Induced Nephrotoxicity through Suppression of Apoptosis, Oxidative Stress, and Inflammation. Nutrients. 2017; 9: 166
• 8 Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler ThrombVasc Biol 2011; 31: 986-1000
• 9 Hsu YH, Chen TH, Chen YC. et al. Urotensin II exerts an anti-apoptotic effect on NRK-52E cells through prostacyclin-mediated peroxisome proliferator-activated receptor alpha and Akt activation. Mol Cell Endocrinol 2013; 381: 168-174
• 10 Jia Z, Zhang Y, Ding G, Heiney KM, Huang S, Zhang A. Role of COX-2/mPGES-1/prostaglandin E2 cascade in kidney injury. Mediators Inflamm 2015; 2015: 147894
• 11 Ranganathan PV, Jayakumar C, Mohamed R, Dong Z, Ramesh G. Netrin-1 regulates the inflammatory response of neutrophils and macrophages, and suppresses ischemic acute kidney injury by inhibiting COX-2-mediated PGE2 production. Kidney Int 2013; 83: 1087-1098
• 12 Ajami M, Eghtesadi S, Pazoki-Toroudi H, Habibey R, Ebrahimi SA. Effect of crocus sativus on gentamicin induced nephrotoxicity. Biol Res 2010; 43: 83-90
• 13 Lee IC, Kim SH, Lee SM. et al. Melatonin attenuates gentamicin-induced nephrotoxicity and oxidative stress in rats. Arch Toxicol 2012; 86: 1527-1536
• 14 Romero F, Pérez M, Chávez M, Parra G, Durante P. Effect of uric acid on gentamicin-induced nephrotoxicity in rats – role of matrix metalloproteinases 2 and 9. Basic Clin Pharmacol Toxicol 2009; 105: 416-424
• 15 Conaghan PG, Dickson J, Bolten W, Cevc G, Rother M. A multicentre, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis. Rheumatology (Oxford) 2013; 52: 1303-1312
• 16 Micklewright R, Lane S, Linley W, McQuade C, Thompson F, Maskrey N. Review article: NSAIDs, gastroprotection and cyclo-oxygenase-II-selective inhibitors. Aliment Pharmacol Ther 2003; 17: 321-332
• 17 Park HK, Lee HW, Lee KS, Choi JS, Jeong BC, Kim HH. Preventive effects of COX-2 inhibitor, celecoxib on renal tubular injury induced by shock wave lithotriptor published correction appears in Urol Res. 2010 Aug;38(4):229. Urol Res. 2010; 38: 223-228
• 18 Kismet K, Akay MT, Abbasoglu O, Ercan A. Celecoxib: a potent cyclooxygenase-2 inhibitor in cancer prevention. Cancer Detect Prev 2004; 28: 127-142
• 19 Kitahara M, Eitner F, Ostendorf T. et al. Selective cyclooxygenase-2 inhibition impairs glomerular capillary healing in experimental glomerulonephritis. J Am Soc Nephrol 2002; 13: 1261-1270
• 20 Miyajima A, Ito K, Asano T, Seta K, Ueda A, Hayakawa M. Does cyclooxygenase-2 inhibitor prevent renal tissue damage in unilateral ureteral obstruction?. J Urol 2001; 166: 1124-1129
• 21 Suddek GM, El-Kenawi AE, Abdel-Aziz A, El-Kashef HA. Celecoxib, a selective cyclooxygenase-2 inhibitor, attenuates renal injury in a rat model of Cisplatin-induced nephrotoxicity. Chemotherapy. 2011; 57: 321-326
• 22 O’Connor JP, Lysz T. Celecoxib, NSAIDs and the skeleton. Drugs Today (Barc) 2008; 44: 693-709
• 23 Ozturk H, Gezici A, Ozturk H. The effect of celecoxib, a selective COX-2 inhibitor, on liver ischemia/reperfusion-induced oxidative stress in rats. Hepatol Res 2006; 34: 76-83
• 24 Koul A, Arora N. Celecoxib mitigates cigarette smoke induced oxidative stress in mice. Indian J Biochem. Biophys 2010; 47: 285-291
• 25 Zhang C, Wang F, Zhang Y. et al. Celecoxib prevents pressure overload-induced cardiac hypertrophy and dysfunction by inhibiting inflammation, apoptosis and oxidative stress. J Cell Mol Med 2016; 20: 116-127
• 26 Abdelrahman RS, Abdelmageed ME. Renoprotective effect of celecoxib against gentamicin-induced nephrotoxicity through suppressing NFκB and caspase-3 signaling pathways in rats. Chem Biol Interact 2020; 315: 108863
• 27 Saleem M, Javed F, Asif M, Baig MK, Arif M. HPLC Analysis and In Vivo Renoprotective Evaluation of Hydroalcoholic Extract of Cucumis melo Seeds in Gentamicin-Induced Renal Damage. Medicina (Kaunas) 2019; 55: 107 Published 2019 Apr 15
• 28 Maciel IS, Silva RB, Morrone FB, Calixto JB, Campos MM. Synergistic effects of celecoxib and bupropion in a model of chronic inflammation-related depression in mice. PLoS One 2013; 8: e77227 Published 2013 Sep 27
• 29 ELLMAN GL. Tissue sulfhydryl groups. Arch BiochemBiophys 1959; 82: 70-77
• 30 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358
• 31 Apaydin Yildirim B, Kordali S, TerimKapakin KA, Yildirim F, AktasSenocak E, Altun S. Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin-induced nephrotoxicity in rats. J Zhejiang Univ Sci B. 2017; 18: 501-511
• 32 Hajihashemi S, Ahmadi M, Chehrei A, Ghanbari F. Ameliorative effect of cotreatment with the methanolic leaf extract of Urtica dioica on acute kidney injury induced by gentamicin in rats. Avicenna J Phytomed 2020; 10: 273-286
• 33 Sahu BD, Kuncha M, Sindhura GJ, Sistla R. Hesperidin attenuates cisplatin-induced acute renal injury by decreasing oxidative stress, inflammation and DNA damage. Phytomedicine. 2013; 20: 453-460
• 34 Ali BH. Agents ameliorating or augmenting experimental gentamicin nephrotoxicity: some recent research. Food Chem Toxicol 2003; 41: 1447-1452
• 35 Tavafi M. Protection of renal tubules against gentamicin induced nephrotoxicity. J Renal Inj Prev 2013; 2: 5-6
• 36 Moreira MA, Nascimento MA, Bozzo TA. et al. Ascorbic acid reduces gentamicin-induced nephrotoxicity in rats through the control of reactive oxygen species. Clin Nutr 2014; 33: 296-301
• 37 Kandemir FM, Ozkaraca M, Yildirim BA. et al. Rutin attenuates gentamicin-induced renal damage by reducing oxidative stress, inflammation, apoptosis, and autophagy in rats. Ren Fail 2015; 37: 518-525
• 38 El Gamal AA, AlSaid MS, Raish M. et al. Beetroot (Beta vulgaris L.) extract ameliorates gentamicin-induced nephrotoxicity associated oxidative stress, inflammation, and apoptosis in rodent model. Mediators Inflamm 2014; 2014: 983952
• 39 Al-Kuraishy HM, Al-Gareeb AI, Al-Nami MS. Irbesartan Attenuates Gentamicin-induced Nephrotoxicity in Rats through Modulation of Oxidative Stress and Endogenous Antioxidant Capacity. Int J Prev Med 2020; 11: 16 . doi: 10.4103/ijpvm.IJPVM_567_18
• 40 Bae EH, Kim IJ, Joo SY. et al. Renoprotective effects of the direct renin inhibitor aliskiren on gentamicin-induced nephrotoxicity in rats. J Renin Angiotensin Aldosterone Syst 2014; 15: 348-361
• 41 Kalayarasan S, Prabhu PN, Sriram N, Manikandan R, Arumugam M, Sudhandiran G. Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats. Eur J Pharmacol 2009; 606: 162-171
• 42 Jaikumkao K, Pongchaidecha A, Thongnak LO. et al. Amelioration of Renal Inflammation, Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity. PLoS One 2016; 11: e0164528
• 43 Nagashio Y, Matsuura Y, Miyamoto J. et al. Hesperidin inhibits development of atopic dermatitis-like skin lesions in NC/Nga mice by suppressing Th17 activity. J Funct Foods 2013; 5: 1633-1641
• 44 Famurewa AC, Maduagwuna EK, Folawiyo AM. et al. Antioxidant, anti-inflammatory, and antiapoptotic effects of virgin coconut oil against antibiotic drug gentamicin-induced nephrotoxicity via the suppression of oxidative stress and modulation of iNOS/NF-ĸB/caspase-3 signaling pathway in Wistar rats. J Food Biochem 2020; 44: e13100
• 45 Zhang P, He D, Song E, Jiang M, Song Y. Celecoxib enhances the sensitivity of non-small-cell lung cancer cells to radiation-induced apoptosis through downregulation of the Akt/mTOR signaling pathway and COX-2 expression [published correction appears in PLoS One. 2019 Oct 30;14(10):e0224843]. PLoS One 2019; 14: e0223760
• 46 Al-Rashed F, Calay D, Lang M. et al. Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling. Sci Rep 2018; 8: 6271
• 47 Subramanian P, Anandan R, Jayapalan JJ, Hashim OH. Hesperidin protects gentamicin-induced nephrotoxicity viaNrf2/HO-1 signaling and inhibits inflammation mediated byNF-κB in rats. J Funct Foods 2015; 13: 89-99
• 48 Yang Y, Gao L. Celecoxib Alleviates Memory Deficits by Downregulation of COX-2 Expression and Upregulation of the BDNF-TrkB Signaling Pathway in a Diabetic Rat Model. J Mol Neurosci 2017; 62: 188-198
• 49 Łanocha-Arendarczyk N, Baranowska-Bosiacka I, Kot K. et al. Expression and Activity of COX-1 and COX-2 in Acanthamoeba sp.-Infected Lungs According to the Host Immunological Status. Int J Mol Sci 2018; 19: 121
• 50 Li Y, Xia W, Zhao F. et al. Prostaglandins in the pathogenesis of kidney diseases. Oncotarget. 2018; 9: 26586-26602
• 51 Anandan R, Subramanian P. Renal protective effect of hesperidin on gentamicin-induced acute nephrotoxicity in male Wistar albino rats. Redox Rep 2012; 17: 219-226
• 52 Kianian F, Seifi B, Kadkhodaee M, Sajedizadeh A, Ahghari P. Protective effects of celecoxib on ischemia reperfusion-induced acute kidney injury: comparing between male and female rats. Iran J Basic Med Sci 2019; 22: 43-48