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Caffeic Acid Phenethyl Ester Modulates Gentamicin-Induced Oxidative Nephrotoxicity in Kidney of Rats

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Abstract

In this study, the modulator effect of caffeic acid phenethyl ester (CAPE) on the oxidative nephrotoxicity of gentamicin in the kidneys of rats was investigated by determining indices of lipid peroxidation and the activities of antioxidant enzymes as well as by histological analyses. Forty female Wistar albino rats were randomly divided into four groups, namely control, gentamicin, CAPE, and gentamicin plus CAPE. On the 12th day of the study, all rats were sacrificed and then blood samples and kidneys were taken. Lipid peroxidation and nitric oxide levels, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) enzyme activities, and histological evaluation were measured in kidneys of rats. Levels of blood urea nitrogen and creatinine were studied in serum. CAPE with gentamicin caused decreases in lipid peroxidation, nitric oxide, urea nitrogen, and creatinine levels, although it caused increases in CAT, GSH-Px, and SOD activities when compared with gentamicin alone. In addition, on histological evaluation, the renal damage caused by gentamicin alone appeared much higher than that caused by CAPE plus gentamicin. It is concluded that oxidative stress plays a critical role in causing gentamicin nephrotoxicity and that this nephrotoxicity may be significantly reduced by CAPE.

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Abbreviations

BUN:

Blood urea nitrogen

CAPE:

Caffeic acid phenethyl ester

CAT:

Catalase

GM:

Gentamicin

GSH-Px:

Glutathione peroxidase

NO:

Nitric oxide

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

References

  1. Nazıroğlu M (2007) New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32:1990–2001

    Article  PubMed  Google Scholar 

  2. Parlakpinar H, Tasdemir S, Polat A et al (2005) Protective role of caffeic acid phenethyl ester (CAPE) on gentamycin-induced acute renal toxicity in rats. Toxicology 207:169–177

    Article  PubMed  CAS  Google Scholar 

  3. Baliga R, Ueda N, Walker PD et al (1999) Oxidant mechanisms in toxic acute renal failure. Drug Metabol Rev 31:971–997

    Article  CAS  Google Scholar 

  4. Ozkaya D, Nazıroğlu M, Armağan A et al (2011) Dietary vitamin C and E modulates oxidative stress induced-kidney and lens injury in diabetic aged male rats through modulating glucose homeostasis and antioxidant systems. Cell Biochem Funct 29:287–293

    Article  PubMed  CAS  Google Scholar 

  5. Yılmaz N, Ilhan S, Nazıroğlu M et al (2011) Ceftriaxone ameliorates cyclosporine A-induced oxidative nephrotoxicity in rat. Cell Biochem Funct 29:102–107

    Article  PubMed  Google Scholar 

  6. Armagan A, Kutluhan S, Yilmaz M et al (2008) Topiramate and vitamin E modulate antioxidant enzyme activities, nitric oxide and lipid peroxidation levels in pentylenetetrazol-induced nephrotoxicity in rats. Basic Clin Pharmacol Toxicol 103(2):166–170

    Article  PubMed  CAS  Google Scholar 

  7. Nazıroğlu M, Karaoğlu A, Aksoy AO (2004) Selenium and high dose vitamin E administration protects cisplatin-induced oxidative damage to renal, liver and lens tissues in rats. Toxicology 195:221–230

    Article  PubMed  Google Scholar 

  8. Ozen S, Akyol O, Iraz M et al (2004) Role of caffeic acid phenethyl ester, an active component of propolis, against cisplatin-induced nephrotoxicity in rats. J Appl Toxicol 24:27–35

    Article  PubMed  Google Scholar 

  9. Nazıroğlu M (2009) Role of selenium on calcium signaling and oxidative stress-induced molecular pathways in epilepsy. Neurochem Res 34:2181–2191

    Article  PubMed  Google Scholar 

  10. Martinez-Salgado C, Lopez-Hernandez FJ, Lopez-Novoa JM (2007) Glomerular nephrotoxicity of aminoglycosides. Toxicol Appl Pharmacol 223:86–98

    Article  PubMed  CAS  Google Scholar 

  11. Gilbert DN, Leggett JE (2010) Aminoglycosides. In: Mandell GL, Bennett JE, Dolin R (eds) Principles and practice of infectious diseases, vol 26. Livingstone, Philadelphia, pp 359–384

    Google Scholar 

  12. Gökçe A, Oktar S, Yönden Z et al (2009) Protective effect of caffeic acid phenethyl ester on cyclosporine A-induced nephrotoxicity in rats. Ren Fail 31:843–847

    Article  PubMed  Google Scholar 

  13. Iraz M, Ozerol E, Gulec M et al (2006) Protective effect of caffeic acid phenethyl ester (CAPE) administration on cisplatin-induced oxidative damage to liver in rat. Cell Biochem Funct 24:357–361

    Article  PubMed  CAS  Google Scholar 

  14. Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431

    Article  PubMed  CAS  Google Scholar 

  15. Woolliams JA, Wiener G, Anderson PH et al (1983) Variation in the activities of glutathione peroxidase and superoxide dismutase and in the concentration of copper in the blood various breed crosses of sheep. Res Vet Sci 34:69–77

    Google Scholar 

  16. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  PubMed  CAS  Google Scholar 

  17. Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    PubMed  CAS  Google Scholar 

  18. Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  19. Sweileh WM (2009) A prospective comparative study of gentamicin- and amikacin-induced nephrotoxicity in patients with normal baseline renal function. Fundam Clin Pharmacol 23:515–520

    Article  PubMed  CAS  Google Scholar 

  20. Balakumar P, Rohilla A, Thangathirupathi A (2010) Gentamicin-induced nephrotoxicity: do we have a promising therapeutic approach to blunt it? Pharmacol Res 62:179–186

    Article  PubMed  CAS  Google Scholar 

  21. Lopez-Novoa JM, Quiros Y, Vicente L et al (2011) New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int 79:33–45

    Article  PubMed  CAS  Google Scholar 

  22. Quiros Y, Vicente-Vicente L, Morales AI et al (2010) An integrative overview on the mechanisms underlying the renal tubular cytotoxicity of gentamycin. Toxicol Sci 119:245–256

    Article  PubMed  Google Scholar 

  23. Morales AI, Detaille D, Prieto M et al (2010) Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway. Kidney Int 77:861–869

    Article  PubMed  CAS  Google Scholar 

  24. Kovacic P, Somanathan R (2008) Unifying mechanism for eye toxicity: electron transfer, reactive oxygen species, antioxidant benefits, cell signaling and cell membranes. Cell Membr Free Radic Res 2:56–69

    Google Scholar 

  25. Sen CK, Packer L (2000) Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 72(2 Suppl):653S–669S

    PubMed  CAS  Google Scholar 

  26. Pekmez H, Ogeturk M, Ozyurt H, Sonmez MF, Colakoglu N, Kus I (2010) Ameliorative effect of caffeic acid phenethyl ester on histopathological and biochemical changes induced by cigarette smoke in rat kidney. Toxicol Ind Health 26:175–182

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors wish to thank Pathologist Ibrahim Zuhtu Altug, MD for the histological evaluation of the kidney samples. Authors also wish to thank Professor Mustafa Naziroglu for his contribution about preparation of the manuscript.

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Authors and Affiliations

  1. Department of Infectious Diseases, Faculty of Medicine, Süleyman Demirel University, Isparta, Turkey

    Fadime Özge Aygün, Füsun Zeynep Akçam & Onur Kaya

  2. Department of Biochemistry and Clinical Biochemistry, Faculty of Medicine, Süleyman Demirel University, Isparta, Turkey

    Betül Mermi Ceyhan & Recep Sütçü

Authors
  1. Fadime Özge Aygün
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  2. Füsun Zeynep Akçam
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  3. Onur Kaya
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  4. Betül Mermi Ceyhan
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  5. Recep Sütçü
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Corresponding author

Correspondence to Onur Kaya.

Additional information

The abstract of the present study was published in the 3rd International Congress on Cell Membranes and Oxidative Stress: Focus on Calcium Signalling and TRP Channels, held June 22–27, 2010 in Isparta, Turkey (www.cmos.org.tr).

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Aygün, F.Ö., Akçam, F.Z., Kaya, O. et al. Caffeic Acid Phenethyl Ester Modulates Gentamicin-Induced Oxidative Nephrotoxicity in Kidney of Rats. Biol Trace Elem Res 145, 211–216 (2012). https://doi.org/10.1007/s12011-011-9172-0

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  • DOI: https://doi.org/10.1007/s12011-011-9172-0

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