Volume 27, Issue 1 (March 2023)                   Physiol Pharmacol 2023, 27(1): 72-79 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Seifi B, Vaezi M, Kadkhodaee M, Kianian F, Sajedizadeh A, Ranjbaran M. N-acetyl cysteine in combination with forelimbs remote ischemic preconditioning improves the contrast-induced nephropathy: an in-vivoexperimental study. Physiol Pharmacol 2023; 27 (1) :72-79
URL: http://ppj.phypha.ir/article-1-1842-en.html
Abstract:   (446 Views)
Introduction: Given some limitations in the efficacy of N-acetyl cysteine (NAC) or remote ischemic preconditioning (RIPC) to prevent contrast-induced nephropathy (CIN), the present study investigated the beneficial effects of NAC alone or in combination with RIPC on CIN prevention.
Methods: Rats were randomly assigned into five groups of eight animals each. Group 1 was sham-operated controls. In group 2, an experimental model of diatrizoate-induced CIN was induced. In groups 3 and 4, NAC (150 mg/kg orally, 24 h before the CIN induction) or RIPC (3 cycles of 4 min/4 min of ischemia and reperfusion in the forelimbs 24 h before the CIN induction) was applied, and both strategies were applied in group 5. 48 hours after the intervention, serum was collected to assess creatinine (Cr) and blood urea nitrogen (BUN) levels. Kidney tissue samples were also kept to evaluate the histology and measure malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity.
Results: Considerable increases in serum Cr (0.82±0.04 vs 0.53±0.03 mg/dl) and BUN (49.87±2.85 vs 22.93±1.11 mg/dl) levels in the CIN group showed renal functional damages compared to the sham group. The morphological changes (2 vs 0 score), increased renal MDA levels (8.11±1.27 vs 3.12±0.52 μmol/100 mg tissue), and decreased renal SOD activity (2.29±0.65 vs 27.32±0.98 U/g tissue) in the CIN group represent a remarkable renal injury and oxidative stress compared to the sham group. The individual use of NAC (serum Cr levels: 0.59±0.01 mg/dl; serum BUN levels: 27.24±1.01 mg/dl; morphological changes: 1 score; renal MDA levels: 4.35±0.58 μmol/100 mg tissue; renal SOD activity: 17.24±1.48 U/g tissue) and RIPC (serum Cr levels: 0.60±0.03 mg/dl; serum BUN levels: 28.78±1.66 mg/dl; morphological changes: 1 score; renal MDA levels: 5.34±0.53 μmol/100 mg tissue; renal SOD activity: 13.11±1.96 U/g tissue) improved all indices above. However, the combination of NAC and RIPC (serum Cr levels: 0.57±0.01 mg/dl; serum BUN levels: 25.32±1.14 mg/dl; morphological changes: 1 score; renal MDA levels: 3.56±0.52 μmol/100 mg tissue; renal SOD activity: 30.54±2.92 U/g tissue) was more effective than other strategies used alone.
Conclusion: The combined use of NAC and RIPC may be more useful in preventing CIN than the individual use of possible additive effects through reducing oxidative stress.
Full-Text [PDF 1019 kb]   (36 Downloads)    

1. Aboubakr HM, Elzohairy EA, Ali AA, Rashed LA, Elkady NK, Soliman AS. Therapeutic effects of N-acetylcysteine against malathion-induced hepatotoxicity. Egypt J Forensic Sci 2019; 9: 34.
2. Agmon Y, Peleg H, Greenfeld Z, Rosen S, Brezis M. Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat. J Clin Invest 1994; 94: 1069-75. [DOI:10.1172/JCI117421]
3. Bafna AA, Shah HC. Remote ischemic preconditioning for prevention of contrast-induced nephropathy–A randomized control trial. Indian Heart J 2020; 72 : 244-7. [DOI:10.1016/j.ihj.2020.04.010]
4. Beckett KR, Moriarity AK, Langer JM. Safe use of contrast media: what the radiologist needs to know. Radiographics 2015; 35: 1738-50. [DOI:10.1148/rg.2015150033]
5. Damasceno AVBS, Barros CAVd, Percario S, Ribeiro Junior RFG, Monteiro AM, Gouveia EHH, et al. Remote ischemic conditioning protects against testicular ischemia∕reperfusion injury in rats. Acta Cir Bras 2020; 35: e202000203. [DOI:10.1590/s0102-865020200020000003]
6. Deng J, Lu Y, Ou J, Shao X, Wang X, Xie H. Remote Ischemic preconditioning reduces the risk of contrast-induced nephropathy in patients with moderate renal impairment undergoing percutaneous coronary angiography: A Meta-Analysis. Kidney Blood Press Res 2020; 45: 549-64. [DOI:10.1159/000507330]
7. Dugbartey GJ, Redington AN. Prevention of contrast-induced nephropathy by limb ischemic preconditioning: underlying mechanisms and clinical effects. Am J Physiol Renal Physiol 2018; 314: F319-28. [DOI:10.1152/ajprenal.00130.2017]
8. Er F, Nia AM, Dopp H, Hellmich M, Dahlem KM, Caglayan E, et al. Ischemic preconditioning for prevention of contrast medium–induced nephropathy: randomized pilot RenPro Trial (Renal Protection Trial). Circulation 2012; 126: 296-303. [DOI:10.1161/CIRCULATIONAHA.112.096370]
9. Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991; 11: 81-128. [DOI:10.1016/0891-5849(91)90192-6]
10. Faghfouri AH, Zarezadeh M, Tavakoli-Rouzbehani OM, Radkhah N, Faghfuri E, Kord-Varkaneh H, et al. The effects of N-acetylcysteine on inflammatory and oxidative stress biomarkers: A systematic review and meta-analysis of controlled clinical trials. Eur J Pharmacol 2020; 884: 173368. [DOI:10.1016/j.ejphar.2020.173368]
11. Geenen RW, Kingma HJ, van der Molen AJ. Contrast-induced nephropathy: pharmacology, pathophysiology and prevention. Insights Imaging 2013; 4: 811-20. [DOI:10.1007/s13244-013-0291-3]
12. Gomes V, de Figueredo CP, Caramori P, Lasevitch R, Bodanese L, Araujo A, et al. N-acetylcysteine does not prevent contrast induced nephropathy after cardiac catheterisation with an ionic low osmolality contrast medium: a multicentre clinical trial. Heart 2005; 91: 774-8. [DOI:10.1136/hrt.2004.039636]
13. Haq MFU, Yip CS, Arora P. The conundrum of contrast-induced acute kidney injury. J Thorac Dis 2020; 12: 1721-7. [DOI:0.21037/jtd.2019.12.88]
14. Honda T, Hirakawa Y, Nangaku M. The role of oxidative stress and hypoxia in renal disease. Kidney Res Clin Pract 2019; 38: 414-26. [DOI:10.23876/j.krcp.19.063]
15. Ighodaro O, Akinloye O. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J Med 2018; 54: 287-93. [DOI:10.1016/j.ajme.2017.09.001]
16. Johnsen J, Pryds K, Salman R, Lofgren B, Kristiansen SB, Botker HE. The remote ischemic preconditioning algorithm: effect of number of cycles, cycle duration and effector organ mass on efficacy of protection. Basic Res Cardiol 2016; 111: 10. [DOI:10.1007/s00395-016-0529-6.]
17. Kedrah AE, Ari E, Alahdab Y, Gul CB, Macunluoglu B, Atakan A, et al. Effect of the direct renin inhibitor aliskiren in the prevention of experimental contrast-induced nephropathy in the rat. Kidney Blood Press Res 2012; 35: 425-30. [DOI:10.1159/000336104]
18. Kelemen JA, Kaserer A, Jensen KO, Stein P, Seifert B, Simmen HP, et al. Prevalence and outcome of contrast-induced nephropathy in major trauma patients. Eur J Trauma Emerg Surg 2020; 1-7. [DOI:10.1007/s00068-020-01496-w]
19. Kianian F, Seifi B, Kadkhodaee M, Sadeghipour HR, Ranjbaran M. Nephroprotection through modifying the apoptotic tnf-α/erk1/2/bax signaling pathway and oxidative stress by long-term sodium hydrosulfide administration in ovalbumin-induced chronic asthma. Immunol Invest 2020; 1-17. [DOI:10.1080/08820139.2020.1858860]
20. 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: 43-8. [DOI:10.22038/ijbms.2018.29644.7156]
21. Kiss N, Hamar P. Histopathological evaluation of contrast-induced acute kidney injury rodent models. Biomed Res Int 2016; 2016: 3763250. [DOI:10.1155/2016/3763250]
22. Kurtoglu T, Durmaz S, Akgullu C, Gungor H, Eryilmaz U, Meteoglu I, et al. Ozone preconditioning attenuates contrast-induced nephropathy in rats. J Surg Res 2015; 195: 604-11. [DOI:10.1016/j.jss.2015.01.0411]
23. Li WH, Wang L, He HY, Chen J, Yu YR. Expression of neutrophil gelatinase‑associated lipocalin in low osmolar contrast‑induced nephropathy in rats and the effect of N‑acetylcysteine. Exp Ther Med 2016; 12: 3175-80. [DOI:10.3892/etm.2016.3779]
24. Liu N, Lei R, Tang MM, Cheng W, Luo M, Xu Q, et al. Autophagy is activated to protect renal tubular epithelial cells against iodinated contrast media‑induced cytotoxicity. Mol Med Rep 2017; 16: 8277-82. [DOI:10.3892/mmr.2017.7599]
25. Mokhtari V, Afsharian P, Shahhoseini M, Kalantar SM, Moini A. A review on various uses of N-acetyl cysteine. Cell J 2017; 19: 11-7. [DOI:10.22074/cellj.2016.4872]
26. Ommati MM, Amjadinia A, Mousavi K, Azarpira N, Jamshidzadeh A, Heidari R. N-acetyl cysteine treatment mitigates biomarkers of oxidative stress in different tissues of bile duct ligated rats. Stress 2020; 1-16. [DOI:10.1080/10253890.2020.1777970]
27. Ow CP, Ngo JP, Ullah MM, Hilliard LM, Evans RG. Renal hypoxia in kidney disease: cause or consequence? Acta Physiol 2018; 222: e12999. [DOI:10.1111/apha.12999]
28. Paoletti F, Mocali A. Changes in CuZn-superoxide dismutase during induced differentiation of murine erythroleukemia cells. Cancer Res 1988; 48: 6674-7.
29. Shetty R, Udupa N, Mutalik S, Kulkarni V, Rao V. Mechanisms and therapeutics of n-acetylcysteine: A recent update. RJPT 2019; 12: 2584-8. [DOI:10.5958/0974-360X.2019.00434.7]
30. Wang F, Yin J, Lu Z, Zhang G, Li J, Xing T, et al. Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase. EBioMedicine 2016; 9: 356-65. [DOI:10.1016/j.ebiom.2016.05.017]
31. Wang JH, Subeq YM, Tsai WC, Lee RP, Hsu BG. Intravenous N-acetylcysteine with saline hydration improves renal function and ameliorates plasma total homocysteine in patients undergoing cardiac angiography. Ren Fail 2008; 30: 527-33. [DOI:10.1080/08860220802064754]
32. Zagidullin NS, Dunayeva AR, Plechev VV, Gilmanov AZ, Zagidullin SZ, Er F, et al. Nephroprotective effects of remote ischemic preconditioning in coronary angiography. Clin Hemorheol Microcirc 2017; 65: 299-307. [DOI:10.3233/CH-16184]
33. Zhang F, Lu Z, Wang F. Advances in the pathogenesis and prevention of contrast-induced nephropathy. Life Sci 2020; 259: 118379. [DOI:10.1016/j.lfs.2020.118379]

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.