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Caffeic acid phenethyl ester suppresses oxidative stress in Escherichia coli-induced pyelonephritis in rats

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Abstract

Although oxidative damage is known to be involved in inflammatory-mediated tissue destruction, modulation of oxygen free radical production represents a new approach to the treatment of inflammatory diseases. Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, has antioxidant, anti-inflammatory and antibacterial properties. For that reason, we aimed to investigate the efficiency of CAPE administration in preventing oxidative damage in pyelonephritis (PYN) caused by Escherichia coli. In this study, 35 Wistar rats were grouped as follows: control, PYN 24 h, PYN 48 h, PYN 72 h, CAPE 24 h, CAPE 48 h and CAPE 72 h. E. coli (1 × 109 c.f.u.) were inoculated into the rats in both PYN and CAPE groups via urethral catheterization. Ten μM/kg-body weight CAPE was injected to the rats in all CAPE groups 24 h before E. coli infection, and injections were repeated at 24-h intervals. Rats were sacrificed 24 h, 48 h and 72 h after infection in both PYN and CAPE groups. Malondialdehyde (MDA) and nitric oxide (NO) levels were significantly increased in kidneys of PYN groups. The activities of the antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and xanthine oxidase (XO) were also elevated by E. coli. However, CAPE administration reduced MDA and NO levels, as well as XO activity, although it increased SOD and GSH-Px activities. Histopathological examination showed that CAPE reduced the inflammation grade induced by E. coli. In conclusion, CAPE administrations decrease the oxidative damage occurring in PYN and therefore could be used for medical management of bacterial nephropathy.

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References

  1. Contran RS, Pennington JE: Urinary tract infection, pyelonephritis and re-flux nephropathy. In: BM Bremmer, FC Rector (eds.) Kidney, pp. 1571–1632, 1981

  2. Rushton HG, Majd M, Jantausch B, Wiedermann BL, Belman B: Renal scarring following reflux and nonreflux pyelonephritis in children: evaluation with 99mtechnetium-dimercaptosuccinic acid scintigraphy. J Urol 147: 1327–1332, 1992. Erratum in: J Urol 148: 898

    Google Scholar 

  3. Sirin A, Emre S, Alpay H, Nayir A, Bilge I, Tanman F (1995) Etiology of chronic renal failure in Turkish children Pediatr Nephrol 9: 549–552

    Article  PubMed  CAS  Google Scholar 

  4. Glauser MP, Meylan P, Bille J (1987) The inflammatory response and tissue damage. The example of renal scars following acute renal infection Pediatr Nephrol 1: 615–622

    Article  PubMed  CAS  Google Scholar 

  5. Glauser MP, Lyons JM, Braude AI (1978) Prevention of chronic experimental pyelonephritis by suppression of acute suppuration J Clin Invest 61: 403–407

    PubMed  CAS  Google Scholar 

  6. Bille J, Glauser MP (1982) Protection against chronic pyelonephritis in rats by suppression of acute suppuration: effect of colchicine and neutropenia J Infect Dis 146: 220–226

    PubMed  CAS  Google Scholar 

  7. Matsumoto T, Mizunoe Y, Sakamoto N, Kumazawa J (1990) Suitability of colchicine and superoxide dismutase for the suppression of renal scarring following an infection with bacteria showing mannose-sensitive pili Nephron 56: 130–135

    Article  PubMed  CAS  Google Scholar 

  8. Roberts JA, Kaack MB, Baskin G (1990) Treatment of experimental pyelonephritis in the monkey J Urol 143: 150–154

    PubMed  CAS  Google Scholar 

  9. Mundi H, Bjorksten B, Svanborg C, Ohman L, Dahlgren C (1991) Extracellular release of reactive oxygen species from human neutrophils upon interaction with Escherichia coli strains causing renal scarring Infect Immun 59: 4168–4172

    PubMed  CAS  Google Scholar 

  10. Roberts JA, Roth JK Jr, Domingue G, Lewis RW, Kaack B, Baskin G (1982) Immunology of pyelonephritis in the primate model. V. Effect of superoxide dismutase J Urol 128: 1394–1400

    PubMed  CAS  Google Scholar 

  11. Gupta R, Verma I, Sharma S, Ganguly NK (2004) Prevention of tissue injury in an ascending mouse model of chronic pyelonephritis–role of free radical scavengers Comp Immunol Microbiol Infect Dis 27: 225–234

    Article  PubMed  CAS  Google Scholar 

  12. Matsumoto T, Mizunoe Y, Ogata N, Tanaka M, Kumazawa J (1991) Role of superoxide in renal scarring following infection by mannose-sensitive piliated bacteria Urol Res 19: 229–233

    Article  PubMed  CAS  Google Scholar 

  13. Matsumoto T, Mizunoe Y, Ogata N, Tanaka M, Takahashi K, Kumazawa J (1992) Antioxidant effect on renal scarring following infection of mannose-sensitive-piliated bacteria Nephron 60: 210–215

    PubMed  CAS  Google Scholar 

  14. Halliwell B, Gutteridge JM (1986) Iron and free radicals: two aspects of antioxidant protection Trends Biochem Sci 11: 372–375

    Article  CAS  Google Scholar 

  15. Halliwell B, Gutteridge JM, Cross CE (1992) Free radicals, antioxidants, and human disease: where are we now? J Lab Clin Med 119: 598–620

    PubMed  CAS  Google Scholar 

  16. Kaur A, Garg UC, Sethi AK, Gorowara S, Sharma S, Ganguly NK (1988) Effect of various oxygen free radical scavengers in preventing tissue injury caused by Escherichia coli in pyelonephritic mice Biochem Int 16: 1083–1093

    PubMed  CAS  Google Scholar 

  17. Rao CV, Desai D, Kaul B, Amin S, Reddy BS (1992) Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth Chem Biol Interact 84: 277–290

    Article  PubMed  CAS  Google Scholar 

  18. Sud’ina GF, Mirzoeva OK, Pushkareva MA, Korshunova GA, Sumbatyan NV, Varfolomeev SD (1993) Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties FEBS Lett 329: 21–24

    Article  PubMed  CAS  Google Scholar 

  19. Michaluart P, Masferrer JL, Carothers AM, Subbaramaiah K, Zweifel BS, Koboldt C, Mestre JR, Grunberger D, Sacks PG, Tanabe T, Dannenberg AJ (1999) Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation Cancer Res 59: 2347–2352

    PubMed  CAS  Google Scholar 

  20. Chen YJ, Shiao MS, Wang SY (2001) The antioxidant caffeic acid phenethyl ester induces apoptosis associated with selective scavenging of hydrogen peroxide in human leukemic HL-60 cells Anticancer Drugs 12: 143–149

    Article  PubMed  CAS  Google Scholar 

  21. Fesen MR, Pommier Y, Leteurtre F, Hiroguchi S, Yung J, Kohn KW (1994) Inhibition of HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE) and related compounds Biochem Pharmacol 48: 595–608

    Article  PubMed  CAS  Google Scholar 

  22. Park EH, Kahng JH (1999) Suppressive effects of propolis in rat adjuvant arthritis Arch Pharm Res 22: 554–558

    PubMed  CAS  Google Scholar 

  23. Grunberger D, Banerjee R, Eisinger K, Oltz EM, Efros L, Caldwell M, Estevez V, Nakanishi K (1988) Preferential cytotoxicity on tumor cells by caffeic acid phenethyl ester isolated from propolis Experientia 44: 230–232

    Article  PubMed  CAS  Google Scholar 

  24. Khayyal MT, el-Ghazaly MA, el-Khatib AS (1993) Mechanisms involved in the antiinflammatory effect of propolis extract Drugs Exp Clin Res 19: 197–203

    PubMed  CAS  Google Scholar 

  25. Bennett RT, Mazzaccaro RJ, Chopra N, Melman A, Franco I (1999) Suppression of renal inflammation with vitamins A and E in ascending pyelonephritis in rats J Urol 161: 1681–1684

    Article  PubMed  CAS  Google Scholar 

  26. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Anal Biochem 72: 248–254

    Article  PubMed  CAS  Google Scholar 

  27. Yoshioka T, Kawada K, Shimada T, Mori M (1979) Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood Am J Obstet Gynecol 135: 372–376

    PubMed  CAS  Google Scholar 

  28. Cortas NK, Wakid NW (1990) Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method Clin Chem 36: 1440–1443

    PubMed  CAS  Google Scholar 

  29. Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase Clin Chem 34: 497–500

    PubMed  CAS  Google Scholar 

  30. Aebi Y (1984) Catalase in vitro Methods Enzymol 105: 121–126

    PubMed  CAS  Google Scholar 

  31. 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 

  32. Prajda N, Weber G (1975) Malignant transformation-linked imbalance: decreased xanthine oxidase activity in hepatomas FEBS Lett 59: 245–259

    Article  PubMed  CAS  Google Scholar 

  33. Sokurenko EV, Hasty DL, Dykhuizen DE (1999) Pathoadaptive mutations: gene loss and variation in bacterial pathogens Trends Microbiol 7: 191–195

    Article  PubMed  CAS  Google Scholar 

  34. Lucchi L, Banni S, Botti B, Cappelli G, Medici G, Melis MP, Tomasi A, Vannini V, Lusvarghi E (1993) Conjugated diene fatty acids in patients with chronic renal failure: evidence of increased lipid peroxidation? Nephron 65: 401–409

    Article  PubMed  CAS  Google Scholar 

  35. Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, Jungers P, Descamps-Latscha B (1996) Advanced oxidation protein products as a novel marker of oxidative stress in uremia Kidney Int 49: 1304–1313

    PubMed  CAS  Google Scholar 

  36. Dillard CJ, Downey JE, Tappel AL (1984) Effect of antioxidants on lipid peroxidation in iron-loaded rats Lipids 19: 127–133

    Article  PubMed  CAS  Google Scholar 

  37. Lee KW, Chun KS, Lee JS, Kang KS, Surh YJ, Lee HJ (2004) Inhibition of cyclooxygenase-2 expression and restoration of gap junction intercellular communication in H-ras-transformed rat liver epithelial cells by caffeic acid phenethyl ester Ann N Y Acad Sci 1030: 501–507

    Article  PubMed  CAS  Google Scholar 

  38. Natarajan K, Singh S, Burke TR Jr, Grunberger D, Aggarwal BB (1996) Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B Proc Natl Acad Sci 93: 9090–9095

    Article  PubMed  CAS  Google Scholar 

  39. Orban Z, Mitsiades N, Burke TR Jr, Tsokos M, Chrousos GP (2000) Caffeic acid phenethyl ester induces leukocyte apoptosis, modulates nuclear factor-kappa B and suppresses acute inflammation Neuroimmunomodulation 7: 99–105

    Article  PubMed  CAS  Google Scholar 

  40. Kirkeboen KA, Strand OA (1999) The role of nitric oxide in sepsis–an overview Acta Anaesthesiol Scand 43: 275–288

    Article  PubMed  CAS  Google Scholar 

  41. Bank N, Kiroycheva M, Singhal PC, Anthony GM, Southan GJ, Szabo C (2000) Inhibition of nitric oxide synthase ameliorates cellular injury in sickle cell mouse kidneys Kidney Int 58: 82–89

    Article  PubMed  CAS  Google Scholar 

  42. Nowicki B, Singhal J, Fang L, Nowicki S, Yallampalli C (1999) Inverse relationship between severity of experimental pyelonephritis and nitric oxide production in C3H/HeJ mice Infect Immun 67: 2421–2427

    PubMed  CAS  Google Scholar 

  43. Song YS, Park EH, Hur GM, Ryu YS, Lee YS, Lee JY, Kim YM, Jin C (2002) Caffeic acid phenethyl ester inhibits nitric oxide synthase gene expression and enzyme activity Cancer Lett 175: 53–61

    Article  PubMed  CAS  Google Scholar 

  44. Sies H (1993) Damage to plasmid DNA by singlet oxygen and its protection Mutat Res 299: 183–191

    Article  PubMed  CAS  Google Scholar 

  45. Santini SA, Marra G, Giardina B, Cotroneo P, Mordente A, Martorana GE, Manto A, Ghirlanda G (1997) Defective plasma antioxidant defenses and enhanced susceptibility to lipid peroxidation in uncomplicated IDDM Diabetes 46: 1853–1858

    Article  PubMed  CAS  Google Scholar 

  46. Parlakpinar H, Tasdemir S, Polat A, Bay-Karabulut A, Vardi N, Ucar M, Acet A (2005) Protective role of caffeic acid phenethyl ester (cape) on gentamicin-induced acute renal toxicity in rats Toxicology 207: 169–177

    Article  PubMed  CAS  Google Scholar 

  47. Koltuksuz U, Ozen S, Uz E, Aydinc M, Karaman A, Gultek A, Akyol O, Gursoy MH, Aydin E (1999) Caffeic acid phenethyl ester prevents intestinal reperfusion injury in rats J Pediatr Surg 34: 1458–1462

    Article  PubMed  CAS  Google Scholar 

  48. Russo A, Longo R, Vanella A (2002) Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin Fitoterapia 73: 21–29

    Article  Google Scholar 

  49. Grilli M, Chiu JJ, Lenardo MJ (1993) NF-kappa B and Rel: participants in a multiform transcriptional regulatory system Int Rev Cytol 143: 1–62

    Article  PubMed  CAS  Google Scholar 

  50. Fietta AM, Morosini M, Meloni F, Bianco AM, Pozzi E (2002) Pharmacological analysis of signal transduction pathways required for mycobacterium tuberculosis-induced IL-8 and MCP-1 production in human peripheral monocytes Cytokine 19: 242–249

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Prof. Dr. Nese K. Biyikli (Department of Pediatric Nephrology, Marmara University, School of Medicine, Istanbul, Turkey) for kindly providing the E. coli ATCC 25922 strain. The authors thank Dr. Sandra Spence (Glasgow/Scotland) for reading the manuscript.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Veterinary Medicine, Mustafa Kemal University, Tayfur Sokmen Campus, Antakya, Hatay, 31034, Turkey

    Sefa Celik & Suat Erdogan

  2. Department of Urology, Medicine Faculty, Mustafa Kemal University, Antakya, Turkey

    Sadik Gorur

  3. Department of Microbiology, Faculty of Veterinary Medicine, Mustafa Kemal University, Antakya, Turkey

    Ozkan Aslantas

  4. Department of Infectious Diseases and Clinical Microbiology, Medicine Faculty, Mustafa Kemal University, Antakya, Turkey

    Sabahattin Ocak

  5. Department of Pathology, Medicine Faculty, Mustafa Kemal University, Antakya, Turkey

    Sibel Hakverdi

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  1. Sefa Celik
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Correspondence to Sefa Celik.

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Celik, S., Gorur, S., Aslantas, O. et al. Caffeic acid phenethyl ester suppresses oxidative stress in Escherichia coli-induced pyelonephritis in rats. Mol Cell Biochem 297, 131–138 (2007). https://doi.org/10.1007/s11010-006-9337-x

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