Yıl: 2022 Cilt: 21 Sayı: 2 Sayfa Aralığı: 132 - 137 Metin Dili: İngilizce DOI: 10.4274/eajem.galenos.2021.45467 İndeks Tarihi: 06-07-2022

Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?

Öz:
Aim: The aim of this study was to examine the basic mechanisms that play a role in the acute nephrotoxicity caused by diclofenac sodium. Materials and Methods: Only water was given to the control group; however, the diclofenac sodium group was group intoxicated by giving water-soluble, 240 mg/kg, oral single dose diclofenac sodium. After 24 hours, all animals were sacrificed and histopathological analyzes were performed. The levels of spesific biomarkers [vascular endothelial growth factor (VEGF), nuclear factor-kappa B (NF-κB), matrix metalloproteinase-9 (MMP-9), metalloproteinase tissue inhibitor-1 (TIMP-1) and carcinoembryonic antigen (CEA)] that may be related to the nephrotoxicity mechanism were evaluated. Results: As a result of biochemical analysis, we found that VEGF, TIMP-1, NF-κB and CEA levels were significantly higher and MMP-9 levels were significantly lower in diclofenac sodium group compared to control group. Nephrotoxicity related histopathological changes were observed in the sections of diclofenac sodium group. Conclusion: This study has shown that the biomarkers we evaluated in the diclofenac sodium-induced acute high-dose intoxication model we created can help us to identify the nephrotoxicity and to explain the nephrotoxicity mechanism with the three main steps (the hemodynamicrelated pathway, the inflammation-related pathway, and the oxidative stress-related pathway). With a simple version of this panel adapted to emergency departments, we may be able to diagnose diclofenac sodium-related nephrotoxicity.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Aydin G, Gökçimen A, Öncü M, Çicek E, Karahan N, Gökalp O. Histopathologic changes in liver and renal tissues induced by different doses of diclofenac sodium in rats. Turkish J Vet Anim Sci. 2003;27:1131-40.
  • 2. FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med. 2001;345:433-2.
  • 3. Baravalia Y, Vaghasiya Y, Chanda S. Hepatoprotective effect of Woodfordia fruticosa Kurz flowers on diclofenac sodium induced liver toxicity in rats. Asian Pac J Trop Med. 2011;4:342-6.
  • 4. Sales GTM, Foresto RD. Drug-induced nephrotoxicity. Rev Assoc Med Bras. 2000;66(Suppl. 1):s82-s90.
  • 5. Mousa AA, Elweza AE, Elbaz HT, Tahoun EAE, Shoghy KM, Elsayed I, et al. Eucalyptus Globulus protects against diclofenac sodium induced hepatorenal and testicular toxicity in male rats. J Tradit Complement Med. 2019;10:521-8.
  • 6. El-Shafei RA, Saleh RM. Pharmacological effects of vitamin C & E on diclofenac sodium intoxicated rats. Biomed Pharmacother. 2016;84:314-22.
  • 7. Choudhury D, Ahmed Z. Drug-induced nephrotoxicity. Med Clin North Am. 1997;81:705-17.
  • 8. Hickey EJ, Raje RR, Reid VE, Gross SM, Ray SD. Diclofenac induced in vivo nephrotoxicity may involve oxidative stress-mediated massive genomic DNA fragmentation and apoptotic cell death. Free Radic Biol Med. 2001;31:139- 52.
  • 9. Schrijvers BF, Flyvbjerg A, De Vriese AS. The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int. 2004;65:2003-17.
  • 10. Estrada CC, Maldonado A, Mallipattu SK. Therapeutic inhibition of VEGF signaling and associated nephrotoxicities. J Am Soc Nephrol. 2019;30:187- 200.
  • 11. Vyas D, Laput G, Vyas AK. Chemotherapy-enhanced inflammation may lead to the failure of therapy and metastasis, OncoTargets Ther. 2014;7:1015.
  • 12. Khames A, Khalaf MM, Gad AM, Abd El-Raouf OM, Kandeil MA. Nicorandil combats doxorubicin-induced nephrotoxicity via amendment of TLR4/P38 MAPK/NFκ-B signaling pathway. Chem Biol Interact. 2019;311:108777.
  • 13. Fattori V, Borghi SM, Guazelli CFS, Giroldo AC, Crespigio J, Bussmann AJC, et al. Vinpocetine reduces diclofenac-induced acute kidney injury through inhibition of oxidative stress, apoptosis, cytokine production, and NF-κB activation in mice. Pharmacol Res. 2017;120:10-22.
  • 14. Borghi SM, Fattori V, Ruiz-Miyazawa KW, Bertozzi MM, Lourenco-Gonzalez Y, Tatakihara R.I, et al. Pyrrolidine dithiocarbamate inhibits mouse acute kidney injury induced by diclofenac by targeting oxidative damage, cytokines and NF-κB activity. Life Sciences. 2018; 208:221-31.
  • 15. Sant B, Rao PL, Nagar DP, Pant SC, Bhasker ASB. Evaluation of abrin induced nephrotoxicity by using novel renal injury markers. Toxicon. 2017;131:20-8.
  • 16. Öztürk ÖG. Matrix Metalloproteinase Enzyme Family. Arch Med Rev J. 2013;22:209-20.
  • 17. Marti HP. Rôle des métalloprotéases matricielles dans la progression des lésions rénales (Role of matrix metalloproteinases in the progression of renal lesions). Presse Med. 2000;29:811-7.
  • 18. Chromek M, Tullus K, Hertting O, Jaremko G, Khalil A, Li Y-H, et al. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in acute pyelonephritis and renal scarring. Pediatr Res. 2003;53:698-705.
  • 19. Hammarström S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. In: Seminars in cancer biology. Academic Press, 1999;67-81.
  • 20. Rani BS, Suchitra MM, Rao PS, Kumar VS. (2019). Serum tumor markers in advanced stages of chronic kidney diseases. Saudi J Kidney Dis Transpl. 2019;30:898.
  • 21. Mittal A, Farooqui SM, Pyrtuh S, Poudel B, Sathian B, Yadav SK. Efficacy of carcinogenic embryonic antigen in differential diagnosis of diseases of pancreas and liver–a comparative study in a tertiary care hospital of Western Nepal. Asian Pac J Cancer Prev. 2012;13:275-7.
  • 22. Tong HL, Dong ZN, Wen XY, Gao J, Wang B, Tian YP. Impact of chronic kidney disease on serum tumor markers concentrations. Chin Med J. 2013;126:274- 9.
  • 23. Kwon YJ, Lee HS, Shim JY, Lee YJ. Serum carcinoembryonic antigen is positively associated with leukocyte count in Korean adults. J Clin Lab Anal. 2018;32:e22291.
  • 24. Jerine Peter S, Evan Prince S. Diclofenac-induced renal toxicity in female Wistar albino rats is protected by the pre-treatment of aqueous leaves extract of Madhuca longifolia through suppression of inflammation, oxidative stress and cytokine formation. Biomed Pharmacother. 2018;98:45-51.
  • 25. Ahmed AY, Gad AM, El-Raouf OMA. Curcumin ameliorates diclofenac sodium-induced nephrotoxicity in male albino rats. J Biochem Mol Toxicol. 2017;31:e21951.
  • 26. Dass E. Diclofenac-induced liver toxicity in albino rats: dose-dependent study. Indian J Res. 2018;7:49-51.
  • 27. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265-75.
  • 28. Naughton CA. Drug-induced nephrotoxicity. Am Fam Physician. 2008;78:743- 50.
  • 29. Laurence LB, Bruce AC, Björn CK, Goodman&Gilman’s, The Pharmacological Basis of Therapeutics, 11th Ed. TheMcGraw-Hill; 2006.
  • 30. Lucas GNC, Leitão ACC, Alencar RL, Xavier RMF, Daher EDF, Silva Junior GBD. Pathophysiological aspects of nephropathy caused by non-steroidal antiinflammatory drugs. Braz J Nephrol. 2019;41:124-30.
  • 31. Yuan HT, Li XZ, Pitera JE, Long DA, Woolf AS. Peritubular capillary loss after mouse acute nephrotoxicity correlates with down-regulation of vascular endothelial growth factor-A and hypoxia-inducible factor-1 alpha. Am J Pathol. 2003;163:2289-301.
  • 32. Schrijvers BF, Flyvbjerg A, De Vriese AS. The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kid Int. 2004;65:2003-17.
  • 33. Makav M, Gelen V, Gedikli S, Atilla Uslu G, Uslu H, Eroğlu HA. Therapeutic effect of Tarantula cubensis extract on indomethacin induced gastric ulcers in rats. Thai J Vet Med. 2020;50:559-66.
  • 34. Hoffmann D, Fuchs TC, Henzler T, Matheis KA, Herget T, Dekant W, et al. Evaluation of a urinary kidney biomarker panel in rat models of acute and subchronic nephrotoxicity. Toxicology. 2010;277:49-58.
  • 35. Shihab FS, Bennett WM, Yi H, Andoh TF. Expression of vascular endothelial growth factor and its receptors Flt-1 and KDR/Flk-1 in chronic cyclosporine nephrotoxicity. Transplantation. 2001;72:164-8.
  • 36. Peng W, Chen J, Jiang Y, Shou Z, Chen Y, Wang H. Non-invasive detection of acute renal allograft rejection by measurement of vascular endothelial growth factor in urine. J Int Med Res. 2007;35:442-9.
  • 37. Wakelin SJ, Marson L, Howie SE, Garden J, Lamb JR, Forsythe JL. The role of vascular endothelial growth factor in the kidney in health and disease. Nephron Physiology. 2004;98:p73-9.
  • 38. Kaur J, Sanyal SN. Diclofenac, a selective COX‐2 inhibitor, inhibits DMH‐ induced colon tumorigenesis through suppression of MCP‐1, MIP‐1α and VEGF. Mol Carcinog. 2011;50:707-18.
  • 39. Dolanbay T, Makav M, Gul HF, Karakurt E. The effect of diclofenac sodium intoxication on the cardiovascular system in rats. Am J Emerg Med. 2021;46: 560-6.
  • 40. Li N, Karin M. Is NF-kappaB the sensor of oxidative stress? FASEB J 1999;13:1137-43.
  • 41. Jiao D, Jiang Q, Liu Y, Ji L. Nephroprotective effect of wogonin against cadmium-induced nephrotoxicity via inhibition of oxidative stress–induced MAPK and NF-κB pathway in Sprague Dawley rats. Hum Exp Toxicol. 2019;38:1082-91.
  • 42. Hamad R, Jayakumar C, Ranganathan P, Mohamed R, El-Hamamy MM, Dessouki AA, et al. Honey feeding protects kidney against cisplatin nephrotoxicity through suppression of inflammation. Clin Exp Pharmacol Physiol. 2015;42:843-8.
  • 43. Caron A, Desrosiers RR, Langlois S, Beliveau R. Ischemia-reperfusion injury stimulates gelatinase expression and activity in kidney glomeruli. Can J Physiol Pharmacol. 2005;83:287-300.
  • 44. Sharma AK, Mauer SM, Kim Y, Michael AF. Altered expression of matrix metalloproteinase-2, TIMP, and TIMP-2 in obstructive nephropathy. J Lab Clin Med. 1995;125:754-61.
  • 45. Kim SY, Moon A. Drug-induced nephrotoxicity and its biomarkers. Biomol Ther. 2012;20:268.
  • 46. Perazella MA. Drug-induced renal failure: update on new medications and unique mechanisms of nephrotoxicity. Am J Med Sci. 2003;325:349-62.
  • 47. Ishizaka N, Ishizaka Y, Toda E, Koike K, Yamakado M, Nagai R. Are serum carcinoembryonic antigen levels associated with carotid atherosclerosis in Japanese men? Arterioscler Thromb Vasc Biol. 2008;28:160‐5.
  • 48. No JI, Yang JY, Hyun HJ, Yeon CS, Choi HJ. Factors associated with serum levels of carcinoembryonic antigen in healthy non‐smokers. Korean J Fam Med. 2013;34:413‐9.
  • 49. Huang CS, Huang LK, Chen CY, Wang WS, Yang SH. Prognostic value of postoperative serum carcinoembryonic antigen levels in colorectal cancer patients with chronic kidney disease. Am J Surg. 2021;221:162-7.
APA Dogruyol S, Akbaş İ, kocak a, AYGORMEZ S, leylek h, AKGOL GUR S, cokbankir o (2022). Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?. , 132 - 137. 10.4274/eajem.galenos.2021.45467
Chicago Dogruyol Sinem,Akbaş İlker,kocak abdullah osman,AYGORMEZ Serpil,leylek habip emrah,AKGOL GUR Sultan Tuna,cokbankir ozge Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?. (2022): 132 - 137. 10.4274/eajem.galenos.2021.45467
MLA Dogruyol Sinem,Akbaş İlker,kocak abdullah osman,AYGORMEZ Serpil,leylek habip emrah,AKGOL GUR Sultan Tuna,cokbankir ozge Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?. , 2022, ss.132 - 137. 10.4274/eajem.galenos.2021.45467
AMA Dogruyol S,Akbaş İ,kocak a,AYGORMEZ S,leylek h,AKGOL GUR S,cokbankir o Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?. . 2022; 132 - 137. 10.4274/eajem.galenos.2021.45467
Vancouver Dogruyol S,Akbaş İ,kocak a,AYGORMEZ S,leylek h,AKGOL GUR S,cokbankir o Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?. . 2022; 132 - 137. 10.4274/eajem.galenos.2021.45467
IEEE Dogruyol S,Akbaş İ,kocak a,AYGORMEZ S,leylek h,AKGOL GUR S,cokbankir o "Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?." , ss.132 - 137, 2022. 10.4274/eajem.galenos.2021.45467
ISNAD Dogruyol, Sinem vd. "Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?". (2022), 132-137. https://doi.org/10.4274/eajem.galenos.2021.45467
APA Dogruyol S, Akbaş İ, kocak a, AYGORMEZ S, leylek h, AKGOL GUR S, cokbankir o (2022). Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?. Eurasian Journal of Emergency Medicine, 21(2), 132 - 137. 10.4274/eajem.galenos.2021.45467
Chicago Dogruyol Sinem,Akbaş İlker,kocak abdullah osman,AYGORMEZ Serpil,leylek habip emrah,AKGOL GUR Sultan Tuna,cokbankir ozge Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?. Eurasian Journal of Emergency Medicine 21, no.2 (2022): 132 - 137. 10.4274/eajem.galenos.2021.45467
MLA Dogruyol Sinem,Akbaş İlker,kocak abdullah osman,AYGORMEZ Serpil,leylek habip emrah,AKGOL GUR Sultan Tuna,cokbankir ozge Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?. Eurasian Journal of Emergency Medicine, vol.21, no.2, 2022, ss.132 - 137. 10.4274/eajem.galenos.2021.45467
AMA Dogruyol S,Akbaş İ,kocak a,AYGORMEZ S,leylek h,AKGOL GUR S,cokbankir o Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?. Eurasian Journal of Emergency Medicine. 2022; 21(2): 132 - 137. 10.4274/eajem.galenos.2021.45467
Vancouver Dogruyol S,Akbaş İ,kocak a,AYGORMEZ S,leylek h,AKGOL GUR S,cokbankir o Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?. Eurasian Journal of Emergency Medicine. 2022; 21(2): 132 - 137. 10.4274/eajem.galenos.2021.45467
IEEE Dogruyol S,Akbaş İ,kocak a,AYGORMEZ S,leylek h,AKGOL GUR S,cokbankir o "Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?." Eurasian Journal of Emergency Medicine, 21, ss.132 - 137, 2022. 10.4274/eajem.galenos.2021.45467
ISNAD Dogruyol, Sinem vd. "Can Spesific Biomarkers Be Used to Enlighten the Major Mechanisms of Acute High Dose Diclofenac Sodium-Related Nephrotoxicity?". Eurasian Journal of Emergency Medicine 21/2 (2022), 132-137. https://doi.org/10.4274/eajem.galenos.2021.45467