Cyclooxygenase biology in renal function – literature review
PDF (Español (España))
HTML (Español (España))


cyclooxygenase 1
cyclooxygenase 2
anti-Inflammatory agents

How to Cite

Goetz Moro M, Vargas Sanchez PK, Lupepsa AC, Baller EM, Nobre Franco GC. Cyclooxygenase biology in renal function – literature review. Rev. Colomb. Nefrol. [Internet]. 2017 Feb. 7 [cited 2022 Aug. 13];4(1):27-3. Available from:


The cyclooxygenase (COX) exists in two main isoforms, COX-1 and COX-2, which are present in the renal system to ensure its homeostasis. However, in different clinical situations, these enzymes can play a physiologic role in maintaining the integrity of this organ, and also be associated with the worsening of tissue injuries/damage. In this sense, an explanation of the true biological function of the isoforms of COX enables a better understanding of the physiology and pathology of the kidney, as well as a better understanding of the consequences of its inhibition by the use of drugs. This review aimed to study the biological role of the COX enzyme in the renal system in different clinical situations.
PDF (Español (España))
HTML (Español (España))


1. Akyazi I, Eraslan E, Gulcubuk A, et al. Long-term aspirin pretreatment in the prevention of cerulein-induced acute pancreatitis in rats. World journal of gastroenterology : WJG 2013;19:2894-2903.

2. Chikazu D, Tomizuka K, Ogasawara T, et al. Cyclooxygenase-2 activity is essential for the osseointegration of dental implants. International journal of oral and maxillofacial surgery 2007;36:441-446.

3. Troxler M, Dickinson K, Homer-Vanniasinkam S. Platelet function and antiplatelet therapy. The British journal of surgery 2007;94:674-682.

4. Sanchez PL, Salgado LM, Ferreri NR, Escalante B. Effect of cyclooxygenase-2 inhibition on renal function after renal ablation. Hypertension 1999;34:848-853.

5. Lomas AL, Grauer GF. The renal effects of NSAIDs in dogs. Journal of the American Animal Hospital Association 2015;51:197-203.

6. Rouzer CA, Marnett LJ. Cyclooxygenases: structural and functional insights. Journal of lipid research 2009;50 Suppl:S29-34.

7. Hao S, Hernandez A, Quiroz-Munoz M, Cespedes C, Vio CP, Ferreri NR. PGE(2) EP(3) receptor downregulates COX-2 expression in the medullary thick ascending limb induced by hypertonic NaCl. American journal of physiology Renal physiology 2014;307:F736-746.

8. Kaminska K, Szczylik C, Lian F, Czarnecka AM. The role of prostaglandin E2 in renal cell cancer development: future implications for prognosis and therapy. Future oncology (London, England) 2014;10:2177-2187.

9. Klawitter J, Klawitter J, McFann K, et al. Bioactive lipid mediators in polycystic kidney disease. Journal of lipid research 2014;55:1139-1149.

10. Liu Y, Rajagopal M, Lee K, et al. Prostaglandin E(2) mediates proliferation and chloride secretion in ADPKD cystic renal epithelia. American journal of physiology Renal physiology 2012;303:F1425-1434.

11. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature: New biology 1971;231:232-235.

12. Marnett LJ, Rowlinson SW, Goodwin DC, Kalgutkar AS, Lanzo CA. Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of catalysis and inhibition. The Journal of biological chemistry 1999;274:22903-22906.

13. Kummer CL, Coelho TC. [Cycloxygenase-2 inhibitors nonsteroid anti- inflammatory drugs: current issues.]. Revista brasileira de anestesiologia 2002;52:498-512.

14. Miller SB. Prostaglandins in health and disease: an overview. Seminars in arthritis and rheumatism 2006;36:37-49.

15. Patrono C, Rocca B. Nonsteroidal antiinflammatory drugs: past, present and future. Pharmacological research : the official journal of the Italian Pharmacological Society 2009;59:285-289.

16. Smith JW, Al-Khamees O, Costall B, Naylor RJ, Smythe JW. Chronic aspirin ingestion improves spatial learning in adult and aged rats. Pharmacology, biochemistry, and behavior 2002;71:233-238.

17. Moncada S, Ferreira SH, Vane JR. Bioassay of prostaglandins and biologically active substances derived from arachidonic acid. Advances in prostaglandin and thromboxane research 1978;5:211-236.

18. Rimon G, Sidhu RS, Lauver DA, et al. Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1. Proceedings of the National Academy of Sciences of the United States of America 2010;107:28-33.

19. Kirkby NS, Chan MV, Lundberg MH, et al. Aspirin-triggered 15-epi-lipoxin A4 predicts cyclooxygenase-2 in the lungs of LPS-treated mice but not in the circulation: implications for a clinical test. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2013;27:3938-3946.

20. Patrignani P, Patrono C. Cyclooxygenase inhibitors: From pharmacology to clinical read-outs. Biochimica et biophysica acta 2015;1851:422-432.

21. Aldrovandi M, Hammond VJ, Podmore H, et al. Human platelets generate phospholipid-esterified prostaglandins via cyclooxygenase-1 that are inhibited by low dose aspirin supplementation. Journal of lipid research 2013;54:3085-3097.

22. Kawahara K, Hohjoh H, Inazumi T, Tsuchiya S, Sugimoto Y. Prostaglandin E-induced inflammation: Relevance of prostaglandin E receptors. Biochimica et biophysica acta 2015;1851:414-421.

23. Hilario MO, Terreri MT, Len CA. Nonsteroidal anti-inflammatory drugs: cyclooxygenase 2 inhibitors. Jornal de pediatria 2006;82:S206-212.

24. Barudzic N, Turjacanin-Pantelic D, Zivkovic V, et al. The effects of cyclooxygenase and nitric oxide synthase inhibition on oxidative stress in isolated rat heart. Molecular and cellular biochemistry 2013;381:301-311.

25. Cairns JA. The coxibs and traditional nonsteroidal anti-inflammatory drugs: a current perspective on cardiovascular risks. The Canadian journal of cardiology 2007;23:125-131.

26. Murtaza G, Karim S, Najam-ul-Haq M, et al. Interaction analysis of aspirin with selective amino acids. Acta poloniae pharmaceutica 2014;71:139-143.

27. Norregaard R, Kwon TH, Frokiaer J. Physiology and pathophysiology of cyclooxygenase-2 and prostaglandin E2 in the kidney. Kidney research and clinical practice 2015;34:194-200.

28. Nantel F, Meadows E, Denis D, Connolly B, Metters KM, Giaid A. Immunolocalization of cyclooxygenase-2 in the macula densa of human elderly. FEBS letters 1999;457:475-477.

29. DeMaria AN, Weir MR. Coxibs--beyond the GI tract: renal and cardiovascular issues. Journal of pain and symptom management 2003;25:S41-49.

30. Moore N, Pollack C, Butkerait P. Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Therapeutics and clinical risk management 2015;11:1061-1075.

31. Batlouni M. [Nonsteroidal anti-inflammatory drugs: cardiovascular, cerebrovascular and renal effects]. Arquivos brasileiros de cardiologia 2010;94:556-563.

32. Ahmetaj-Shala B, Kirkby NS, Knowles R, et al. Evidence that links loss of cyclooxygenase-2 with increased asymmetric dimethylarginine: novel explanation of cardiovascular side effects associated with anti- inflammatory drugs. Circulation 2015;131:633-642.

33. Zhang MZ, Wang JL, Cheng HF, Harris RC, McKanna JA. Cyclooxygenase-2 in rat nephron development. The American journal of physiology 1997;273:F994-1002.

34. Khan KN, Venturini CM, Bunch RT, et al. Interspecies differences in renal localization of cyclooxygenase isoforms: implications in nonsteroidal antiinflammatory drug-related nephrotoxicity. Toxicologic pathology 1998;26:612-620.

35. Dubois RN, Abramson SB, Crofford L, et al. Cyclooxygenase in biology and disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1998;12:1063-1073.

36. Lipsky PE. Defining COX-2 inhibitors. The Journal of rheumatology Supplement 2000;60:13-16.

37. Curiel RV, Katz JD. Mitigating the cardiovascular and renal effects of NSAIDs. Pain medicine (Malden, Mass) 2013;14 Suppl 1:S23-28.

38. Harris RC. Physiologic and pathophysiologic roles of cyclooxygenase-2 in the kidney. Transactions of the American Clinical and Climatological Association 2013;124:139-151.

39. Wang C, Luo Z, Kohan D, et al. Thromboxane prostanoid receptors enhance contractions, endothelin-1, and oxidative stress in microvessels from mice with chronic kidney disease. Hypertension 2015;65:1055- 1063.

40. 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 of inflammation 2015;2015:147894.

41. Calistro Neto JP, Torres Rda C, Goncalves GM, et al. Parecoxib reduces renal injury in an ischemia/reperfusion model in rats. Acta cirurgica brasileira / Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia 2015;30:270-276.

42. Tunctan B, Korkmaz B, Sari AN, et al. Contribution of iNOS/sGC/PKG pathway, COX-2, CYP4A1, and gp91(phox) to the protective effect of 5,14-HEDGE, a 20-HETE mimetic, against vasodilation, hypotension, tachycardia, and inflammation in a rat model of septic shock. Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society 2013;33:18-41.

43. Liu HB, Meng QH, Huang C, Wang JB, Liu XW. Nephroprotective Effects of Polydatin against Ischemia/Reperfusion Injury: A Role for the PI3K/Akt Signal Pathway. Oxidative medicine and cellular longevity 2015;2015:362158.

44. Wang ZS, Liu XH, Wang M, et al. Metformin attenuated the inflammation after renal ischemia/reperfusion and suppressed apoptosis of renal tubular epithelial cell in rats. Acta cirurgica brasileira / Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia 2015;30:617-623.

45. Feitoza CQ, Goncalves GM, Semedo P, et al. Inhibition of COX 1 and 2 prior to renal ischemia/reperfusion injury decreases the development of fibrosis. Molecular medicine (Cambridge, Mass) 2008;14:724-730.

46. Suleyman Z, Sener E, Kurt N, Comez M, Yapanoglu T. The effect of nimesulide on oxidative damage inflicted by ischemia-reperfusion on the rat renal tissue. Renal failure 2015;37:323-331.

47. Gonzalez AA, Green T, Luffman C, Bourgeois CR, Gabriel Navar L,Prieto MC. Renal medullary cyclooxygenase-2 and (pro)renin receptor expression during angiotensin II-dependent hypertension. American journal of physiology Renal physiology 2014;307:F962-970.

48. Kamata M, Hosono K, Fujita T, Kamata K, Majima M. Role of cyclooxygenase-2 in the development of interstitial fibrosis in kidneys following unilateral ureteral obstruction in mice. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2015;70:174-180.

49. Ibrahim NH, Gregoire M, Devassy JG, et al. Cyclooxygenase product inhibition with acetylsalicylic acid slows disease progression in the Han:SPRD-Cy rat model of polycystic kidney disease. Prostaglandins & other lipid mediators 2015;116-117:19-25.

50. Xu T, Wang NS, Fu LL, Ye CY, Yu SQ, Mei CL. Celecoxib inhibits growth of human autosomal dominant polycystic kidney cyst-lining epithelial cells through the VEGF/Raf/MAPK/ERK signaling pathway. Molecular biology reports 2012;39:7743-7753.

51. Mohamed R, Jayakumar C, Ranganathan PV, Ganapathy V, Ramesh G. Kidney proximal tubular epithelial-specific overexpression of netrin-1 suppresses inflammation and albuminuria through suppression of COX- 2-mediated PGE2 production in streptozotocin-induced diabetic mice. The American journal of pathology 2012;181:1991-2002.

52. Jia Z, Sun Y, Liu S, Liu Y, Yang T. COX-2 but not mPGES-1 contributes to renal PGE2 induction and diabetic proteinuria in mice with type-1 diabetes. PloS one 2014;9:e93182.

53. Dey A, Williams RS, Pollock DM, et al. Altered kidney CYP2C and cyclooxygenase-2 levels are associated with obesity-related albuminuria. Obesity research 2004;12:1278-1289.

54. Sun Y, Jia Z, Liu G, et al. PPARgamma Agonist Rosiglitazone Suppresses Renal mPGES-1/PGE2 Pathway in db/db Mice. PPAR research 2013;2013:612971.

55. Komers R, Zdychova J, Cahova M, Kazdova L, Lindsley JN, Anderson S. Renal cyclooxygenase-2 in obese Zucker (fatty) rats. Kidney international 2005;67:2151-2158.

56. Liu YW, Zhu X, Cheng YQ, et al. Ibuprofen attenuates nephropathy in streptozotocininduced diabetic rats. Molecular medicine reports 2016;13:5326-5334.

57. Song KI, Park JY, Lee S, et al. Protective effect of tetrahydrocurcumin against cisplatin-induced renal damage: in vitro and in vivo studies. Planta medica 2015;81:286-291.

58. Feng L, Xia Y, Garcia GE, Hwang D, Wilson CB. Involvement of reactive oxygen intermediates in cyclooxygenase-2 expression induced by interleukin-1, tumor necrosis factor-alpha, and lipopolysaccharide. The Journal of clinical investigation 1995;95:1669-1675.

59. Fujihara CK, Antunes GR, Mattar AL, et al. Cyclooxygenase-2 (COX-2) inhibition limits abnormal COX-2 expression and progressive injury in the remnant kidney. Kidney international 2003;64:2172-2181.

60. Kinsey GR, Sharma R, Okusa MD. Regulatory T cells in AKI. Journal of the American Society of Nephrology : JASN 2013;24:1720-1726.

61. Hao CM, Breyer MD. Physiologic and pathophysiologic roles of lipid mediators in the kidney. Kidney international 2007;71:1105-1115.

62. Nasrallah R, Hassouneh R, Hebert RL. Chronic kidney disease: targeting prostaglandin E2 receptors. American journal of physiology Renal physiology 2014;307:F243-250.

63. Zhang Y, Guan Y, Schneider A, Brandon S, Breyer RM, Breyer MD. Characterization of murine vasopressor and vasodepressor prostaglandin E(2) receptors. Hypertension 2000;35:1129-1134.

64. Breyer MD, Breyer RM. Prostaglandin E receptors and the kidney. American journal of physiology Renal physiology 2000;279:F12-23.
No national or foreign publication may partially or totally reproduce or translate Revista Colombiana de Nefrología articles or abstracts without prior written permission from the journal’s Editorial Board.




Download data is not yet available.