Molecular and Cellular Biochemistry

, Volume 450, Issue 1–2, pp 43–52 | Cite as

N-(2-hydroxyphenyl)acetamide and its gold nanoparticle conjugation prevent glycerol-induced acute kidney injury by attenuating inflammation and oxidative injury in mice

  • Rehan Ahmed Siddiqui
  • Shabana Usman SimjeeEmail author
  • Nurul Kabir
  • Muhammad Ateeq
  • M. Raza Shah
  • Syed Saad Hussain


The protective activity of N-(2-hydroxyphenyl)acetamide (NA-2) and NA-2-coated gold nanoparticles (NA-2-AuNPs) in glycerol-treated model of acute kidney injury (AKI) in mice was investigated. NA-2 (50 mg/kg) and NA-2-AuNPs (30 mg/kg) were given to the animals for four days followed by 24-h water deprivation and injection of 50% glycerol (10 ml/kg im). The animals were sacrificed on the next day. Blood and kidneys were collected for biochemical investigations (urea and creatinine), histological studies (hematoxylin and eosin; and periodic acid-Schiff staining), immunohistochemistry (actin and cyclooxygenase-2, Cox-2), and real-time RT-PCR (inducible nitric oxide synthase, iNOS; nuclear factor-κB p50, NFκB; hemeoxygenase-1, HO-1; and kidney injury molecule-1, Kim-1). NA-2 protected renal tubular necrosis and inflammation, though the result of NA-2-AuNPs was better than compound alone and it also exhibited the activity at far less dose. The test compound and its gold nano-formulation decreased the levels of serum urea and creatinine level in the treated animals. Both NA-2 and NA-2-AuNPs also conserved actin cytoskeleton, and lowered COX-2 protein expression. Moreover, the mRNA expressions of iNOS and NFkB p50 were down-regulated, and HO-1 and Kim-1 genes were up-regulated. We conclude that NA-2 and NA-2-AuNPs ameliorates kidney inflammation and injury in glycerol-induced AKI animal model via anti-oxidant and anti-inflammatory mechanisms which make it a suitable candidate for further studies. We believe that these findings will contribute in the understanding of the mechanism of action of paracetamol-like drugs and can be considered for clinical research for the prevention of AKI.


Acute kidney injury N-(2-hydroxyphenyl)acetamide Glycerol Rhabdomyolysis Gold nanoparticles 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Robbins S, Cotran R, Kumar V (1979) Pathologic basis of disease WB Saunders, Philadelphia, p. 1591Google Scholar
  2. 2.
    Bosch X, Poch E, Grau JM (2009) Rhabdomyolysis and acute kidney injury. N Engl J Med 361(1):62–72CrossRefGoogle Scholar
  3. 3.
    Davidson S, Boon NA, College NR (2010) Davidson’s principles and practice of medicine, 21st edn. Elsevier, AmsterdamGoogle Scholar
  4. 4.
    Kumar P, Kumar CM (2009) Clark clinical medicine, 7th edn. Saunders Press, LondonGoogle Scholar
  5. 5.
    Lameire N, Van Biesen W, Vanholder R (2006) The changing epidemiology of acute renal failure. Nat Clin Pract Nephrol 2(7):364–377CrossRefGoogle Scholar
  6. 6.
    Kim JH, Lee SS, Jung MH, Yeo HD, Kim H-J, Yang JI et al (2010) N-acetylcysteine attenuates glycerol-induced acute kidney injury by regulating MAPKs and Bcl-2 family proteins. Nephrol Dial Transplant 25(5):1435–1443CrossRefGoogle Scholar
  7. 7.
    Fishman AI, Alexander B, Eshghi M, Choudhury M, Konno S (2012) Nephrotoxin-induced renal cell injury involving biochemical alterations and its prevention with antioxidant. J Clin Med Res 4(2):95Google Scholar
  8. 8.
    Park CH, Tanaka T, Cho EJ, Park JC, Shibahara N, Yokozawa T (2012) Glycerol-induced renal damage improved by 7-O-galloyl-d-sedoheptulose treatment through attenuating oxidative stress. Biol Pharm Bull 35(1):34–41CrossRefGoogle Scholar
  9. 9.
    Ustundag S, Yalcin O, Sen S, Cukur Z, Ciftci S, Demirkan B (2008) Experimental myoglobinuric acute renal failure: the effect of vitamin C. Ren Fail 30(7):727–735CrossRefGoogle Scholar
  10. 10.
    Aydogdu N, Atmaca G, Yalcin O, Taskiran R, Tastekin E, Kaymak K (2006) Protective effects of l-carnitine on myoglobinuric acute renal failure in rats. Clin Exp Pharmacol Physiol 33(1-2):119–124CrossRefGoogle Scholar
  11. 11.
    Korrapati MC, Shaner BE, Schnellmann RG (2012) Recovery from glycerol-induced acute kidney injury is accelerated by suramin. J Pharmacol Exp Ther 341(1):126–136CrossRefGoogle Scholar
  12. 12.
    Singh AP, Singh AJ, Singh N (2011) Pharmacological investigations of Punica granatum in glycerol-induced acute renal failure in rats. Ind J Pharmacol 43(5):551CrossRefGoogle Scholar
  13. 13.
    Hu L, Yu T, Jia Z (1996) Experimental study of the protective effects of astragalus and salvia miltiorrhiza bunge on glycerol induced acute renal failure in rabbits. Zhonghua Wai Ke Za Zhi 34(5):311–314Google Scholar
  14. 14.
    Chander V, Chopra K (2006) Protective effect of resveratrol, a polyphenolic phytoalexin on glycerol-induced acute renal failure in rat kidney. Ren Fail 28(2):161–169CrossRefGoogle Scholar
  15. 15.
    Chander V, Singh D, Chopra K (2003) Catechin, a natural antioxidant protects against rhabdomyolysis-induced myoglobinuric acute renal failure. Pharmacol Res 48(5):503–509CrossRefGoogle Scholar
  16. 16.
    Chander V, Singh D, Chopra K (2005) Reversal of experimental myoglobinuric acute renal failure in rats by quercetin, a bioflavonoid. Pharmacol 73(1):49–56CrossRefGoogle Scholar
  17. 17.
    Baliga R, Ueda N, Walker PD, Shah SV (1997) Oxidant mechanisms in toxic acute renal failure. Am J Kid Dis 29(3):465–477CrossRefGoogle Scholar
  18. 18.
    Cil O, Ertunc M, Gucer KS, Ozaltin F, Iskit AB, Onur R (2012) Endothelial dysfunction and increased responses to renal nerve stimulation in rat kidneys during rhabdomyolysis-induced acute renal failure: role of hydroxyl radical. Ren Fail 34(2):211–220CrossRefGoogle Scholar
  19. 19.
    Gozzelino R, Jeney V, Soares MP (2010) Mechanisms of cell protection by heme oxygenase-1. Ann Rev Pharmacol Toxicol 50:323–354CrossRefGoogle Scholar
  20. 20.
    Perveen K, Hanif F, Jawed H, Simjee SU (2013) Protective efficacy of N-(2-hydroxyphenyl) acetamide against adjuvant-induced arthritis in rats. BioMed Res Int. Google Scholar
  21. 21.
    Hanif F, Perveen K, Jawed H, Ahmed A, Malhi SM, Jamall S et al (2014) N-(2-hydroxyphenyl) acetamide (NA-2) and Temozolomide synergistically induce apoptosis in human glioblastoma cell line U87. Cancer Cell Int 14(1):133CrossRefGoogle Scholar
  22. 22.
    Martis EA, Badve RR, Degwekar MD (2012) Nanotechnology based devices and applications in medicine: an overview. Chron Young Sci 3(1):68CrossRefGoogle Scholar
  23. 23.
    Larsson L, Aperia A, Elinder G (1983) Structural and functional development of the nephron. Acta Paediatr Scand Suppl 305:56–60CrossRefGoogle Scholar
  24. 24.
    Figueiredo JF, Bertels IM, Gontijo JA (2008) Actin cytoskeletal and functional studies of the proximal convoluted tubules after preservation. Transplant Proc 40:3311–3315CrossRefGoogle Scholar
  25. 25.
    Merrill GF et al (2004) Acetaminophen and myocardial infarction in dogs. Am J Physiol 287:H1913–H1920Google Scholar
  26. 26.
    Gilmore TD (2006) Introduction to NF-kB: players, pathways, perspectives. Oncogene 25(51):6680–6684CrossRefGoogle Scholar
  27. 27.
    Perkins ND (2007) Integrating cell-signaling pathways with NF-κB and IKK function. Nat Rev Mol Cell Biol 8(1):49–62CrossRefGoogle Scholar
  28. 28.
    Sanz AB, Sanchez-Niño MD, Ramos AM, Moreno JA, Santamaria B, Ruiz-Ortega M et al (2010) NF-κB in renal inflammation. J Am Soc Nephrol 21(8):1254–1262CrossRefGoogle Scholar
  29. 29.
    Lawrence T (2009) The nuclear factor NF-κB pathway in inflammation. Cold Spring Harb Perspect Biol 1(6):a001651CrossRefGoogle Scholar
  30. 30.
    Hayden MS, Ghosh S (2008) Shared principles in NF-κB signaling. Cell 132(3):344–362CrossRefGoogle Scholar
  31. 31.
    Mungrue IN, Husain M, Stewart DJ (2004) The role of NOS in heart failure: lessons from murine genetic models. The role of nitric oxide in heart failure: Springer, New York. pp 113–128CrossRefGoogle Scholar
  32. 32.
    Kikuchi G, Yoshida T, Noguchi M (2005) Heme oxygenase and heme degradation. Biochem Biophy Res Commun 338(1):558–567CrossRefGoogle Scholar
  33. 33.
    Piantadosi CA, Withers CM, Bartz RR et al (2011) Heme oxygenase-1 couples activation of mitochondrial biogenesis to anti-inflammatory cytokine expression. J Biol Chem 286(18):16374–16385CrossRefGoogle Scholar
  34. 34.
    Yang L, Brooks CR, Xiao S et al (2015) KIM-1–mediated phagocytosis reduces acute injury to the kidney. J Clin Investig 125(4):1620–1636CrossRefGoogle Scholar
  35. 35.
    Lim AI, Tang SC, Lai KN, Leung JC (2013) Kidney injury molecule-1: More than just an injury marker of tubular epithelial cells? J Cell Physiol 228(5):917–924CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Rehan Ahmed Siddiqui
    • 1
    • 3
  • Shabana Usman Simjee
    • 1
    • 2
    Email author
  • Nurul Kabir
    • 4
  • Muhammad Ateeq
    • 2
    • 5
  • M. Raza Shah
    • 2
  • Syed Saad Hussain
    • 2
  1. 1.Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological ScienceUniversity of KarachiKarachiPakistan
  2. 2.H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological ScienceUniversity of KarachiKarachiPakistan
  3. 3.Department of ResearchZiauddin UniversityKarachiPakistan
  4. 4.Institute of Biological Sciences, Faculty of ScienceUniversity of MalayaKuala LumpurMalaysia
  5. 5.Abdul Wali Khan UniversityMardanPakistan

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