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Effects of Caffeic Acid Phenethyl Ester (CAPE) on Sepsis in Rats

Inflammation volume 31, pages 273–280 (2008)Cite this article

Abstract

Sepsis is still a major cause of the high mortality rate in the intensive care unit. Many studies have been published about the severity of sepsis, but the cause of mortality in sepsis and multiorgan failure is still obscure. This study investigated the effects of caffeic acid phenethyl ester (CAPE) particularly on the inflammatory and related histopathological changes in the lung, liver and kidney in an experimental sepsis model. Forty Sprague Dawley rats were used in this study, and were divided into four groups of ten rats each, as follows: Group I was given intraperitoneal saline infusion treatment. Group II was given intraperitoneal CAPE infusion treatment. Sepsis was induced in the animals in Group III (sepsis with saline infusion), while Group IV rats underwent induced sepsis plus CAPE infusion treatment (sepsis with CAPE infusion). Sampling was performed 48 h after treatment. The induction of sepsis resulted in a significant increase in serum glucose, leukocytes, urea, creatinine, LDH levels in BAL, plasma MDA, AST and ALT levels in the sepsis + saline group. The use of CAPE significantly decreased these parameters. Histopathological examination revealed less congestion, portal inflammation, and focal necrosis of the liver, and less congestion, edema, and emphysematous and inflammatory changes in the lung in the sepsis + CAPE group than in the other groups. These results support that CAPE may be used for the treatment of organ failure during sepsis.

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References

  1. Alberti, C., C. Brun-Buisson, H. Burchardi, et al. 2002. Epidemiology of sepsis and infection in ICU patients from an international multicenter cohort study. Intensive Care Med. 28:108–121.

    PubMed  Article  Google Scholar 

  2. Kirkeboen, K. A., and O. A. Strand. 1999. The role of nitric oxide in sepsis—an overview. Acta Anesthesiol. Scand. 43:275–288.

    Article  CAS  Google Scholar 

  3. O’Reilly, M., D. E. Newcomb, and D. Remick. 1999. Endo-toxin, sepsis, and the primrose path. Shock 12:411–420.

    PubMed  Article  CAS  Google Scholar 

  4. Schröder, J., V. Khalke, K. H. Staubach, et al. 1998. Gender differences in human sepsis. Arch. Surg. 133:1200–1205.

    PubMed  Article  Google Scholar 

  5. Fiorentino, D., A. Zlotnik, T. Mosmann, et al. 1991. IL-10 inhibits cytokine production by activated macrophages. J. Immunol. 147:3815–3822.

    PubMed  CAS  Google Scholar 

  6. Remick, D. G., G. R. Bolgos, J. Siddiqui, et al. 2002. Six at six: interleukin-6 measured 6 h after the initiation of sepsis predicts mortality over 3 days. Shock 17:463–467.

    PubMed  Article  Google Scholar 

  7. Tate, R. M., H. G. Morris, W. R. Schroeder, et al. 1984. Oxygen metabolites stimulate thromboxane production and vasoconstriction in isolated saline-perfused rabbit lung. J. Clin. Invest. 74:608.

    PubMed  Article  CAS  Google Scholar 

  8. Hotter, G., D. Closa, N. Prats, et al. 1997. Free radical enhancement promotes leukocytes recruitment through a PAF and LTB4 dependent mechanism. Free Radic. Biol. Med. 22:947–954.

    PubMed  Article  CAS  Google Scholar 

  9. İlhan, A., Ö. Akyol, A. Gürel, et al. 2004. Protective effects of caffeic acid phenethyl ester against experimental allergic encephalomyelitis-induced oxidative stress in rats. Free Radic. Biol. Med. 37:386–394.

    PubMed  Article  Google Scholar 

  10. Ozyurt, H., B. Ozyurt, K. Koca, et al. 2007. Caffeic acid phenethyl ester (CAPE) protects rat skeletal muscle against ischemia-reperfusion-induced oxidative stress. Vascul. Pharmacol. 47(2–3):108–112, Aug–Sep.

    PubMed  Article  CAS  Google Scholar 

  11. Turkyilmaz, S., E. Alhan, C. Ercin, et al. 2008. Effects of caffeic acid phenethyl ester on pancreatitis in rats. J. Surg. Res. 145(1):19–24. Epub 2007 Oct 29, Mar.

    PubMed  Article  CAS  Google Scholar 

  12. Song, Y. S., E. H. Park, G. M. Hur, et al. 2002. Caffeic acid phenethyl ester inhibits nitric oxide synthase gene expression and enzyme activity. Cancer Lett. 175:53–61.

    PubMed  Article  CAS  Google Scholar 

  13. Correa, P. B., J. A. Pancoto, G. R. de Oliveira-Pelegrin, et al. 2007. Participation of iNOS-derived NO in hypothalamic activation and vasopressin release during polymicrobial sepsis. J. Neuroimmunol. 183:17–25.

    PubMed  Article  CAS  Google Scholar 

  14. Nose, K., M. Wasa, and A. Okada. 2002. Gut glutamine metabolism at different stages of sepsis in rats. Surg. Today 32:695–700.

    PubMed  Article  CAS  Google Scholar 

  15. Yılmaz, H. R., E. Uz, N. Yücel, et al. 2004. Protective effect of caffeic acid phenetyl ester (CAPE) on lipid peroxidation and antioxidant enzymes in diabetic rat liver. J. Biochem. Mol. Toxicol. 18:234–238.

    PubMed  Article  Google Scholar 

  16. Aydoğdu, N., G. Atmaca, Ö. Yalçın, et al. 2004. Effects of caffeic acid phenethyl ester on glycerol-induced acute renal failure in rats. Clin. Experimental. Pharmacol. Physiol. 31:575–579.

    Article  Google Scholar 

  17. Yağmurca, M., H. Erdoğan, M. Iraz, et al. 2004. Caffeic acid phenethyl ester as a protective agent against doxorubicin nephrotoxicity in rats. Clin. Chim. Acta. 348(1–2):27–34.

    PubMed  Article  Google Scholar 

  18. Sookhai, S., J. J. Wang, M. McCourt, et al. 2002. A novel therapeutic strategy for attenuating neutrophil-mediated lung injury in vivo. Ann. Surg. 235(2):285–291.

    PubMed  Article  Google Scholar 

  19. Sahna, E., H. Parlakpinar, F. Ozturk, et al. 2003. The protective effects of physiological and pharmacological concentrations of melatonin on renal ischemia-reperfusion injury in rats. Urol. Res. 31:188–193.

    PubMed  Article  CAS  Google Scholar 

  20. Ozveri, E. S., A. Bozkurt, G. Haklar, et al. 2001. Estrogens ameliorate remote organ inflammation induced by burn injury in rats. Inflamm. Res. 50:585–591.

    PubMed  Article  CAS  Google Scholar 

  21. Yu, M., D. Shao, R. Yang, et al. 2007. Effects of ketamine on pulmonary inflammatory responses and survival in rats exposed to polymicrobial sepsis. J. Pharm. Pharmaceut. Sci. 10:434–442.

    Google Scholar 

  22. Erikoğlu, M., M. Sahin, S. Ozer, et al. 2005. Effects of gender on the severity of sepsis. Surg. Today 35:467–472.

    PubMed  Article  Google Scholar 

  23. Bohles, H. 1997. Antioxidative vitamins in prematurely and maturely born infants. Int. J. Vit. Nutr. Res. 67:321–328.

    CAS  Google Scholar 

  24. Heller, A. R., G. Groth, S. C. Heller, et al. 2001. N-Acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis in intensive care unit patients. Crit. Care Med. 29:272–276.

    PubMed  Article  CAS  Google Scholar 

  25. Grunberger, D., R. Banerjee, K. Eisinger, et al. 1988. Preferential cytotoxicity on tumor cells by caffeic acid phenethyl ester isolated from propolis. Experientia 44:230–232.

    PubMed  Article  CAS  Google Scholar 

  26. Sahin, O., O. Sulak, Y. Yavuz, et al. 2006. Lithium-induced lung toxicity in rats: the effect of caffeic acid phenethyl ester (CAPE). Pathology 38:58–62.

    PubMed  Article  CAS  Google Scholar 

  27. Su, Z. Z., D. Grunberger, and P. B. Fisher. 1991. Suppression of adenovirus type five EIA-mediated transformation and expression of the transformed phenotype by caffeic acid phenethyl ester (CAPE). Mol. Carcinog. 4:231–242.

    PubMed  Article  CAS  Google Scholar 

  28. Hosnuter, M., A. Gurel, O. Babuccu, et al. 2004. The effect of CAPE on lipid peroxidation and nitric oxide levels in the plasma of rats following thermal injury. Burns 30:121–125.

    PubMed  Article  Google Scholar 

  29. Sener, G., H. Toklu, C. Kapucu, et al. 2005. Melatonin protects against oxidative organ injury in a rat model of sepsis. Surg. Today. 35:52–59.

    PubMed  Article  CAS  Google Scholar 

  30. Brooks, H. F., C. K. Osabutey, R. F. Moss, et al. 2007. Caecal ligation and puncture in the rat mimics the pathophysiological changes in human sepsis and causes multi-organ dysfunction. Metab. Brain Dis. 22:353–373.

    PubMed  Article  CAS  Google Scholar 

  31. Galley, H. F., M. J. Davies, and N. R. Webster. 1996. Xanthine oxidase activity and free radical generation in patients with sepsis syndrome. Crit. Care Med. 24:1649–1653.

    PubMed  Article  CAS  Google Scholar 

  32. Irmak, M. K., E. Fadillioglu, M. Gulec, et al. 2002. Effects of electromagnetic radiation from a cellular telephone on the oxidant and antioxidant levels in rabbits. Cell. Biochem. Funct. 20:279–283.

    PubMed  Article  CAS  Google Scholar 

  33. Draper, H. H., and M. Hadley. 1990. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol. 186:421–431.

    PubMed  Article  CAS  Google Scholar 

  34. Razavi, H. M., R. Werhun, J. A. Scott, et al. 2002. Effects of inhaled nitric oxide in a mouse model of sepsis-induced acute lung injury. Crit. Care Med. 30:868–873.

    PubMed  Article  CAS  Google Scholar 

  35. Akyol, A., H. Ulusoy, M. Imamoglu, et al. 2006. Does propofol or caffeic acid phenethyl ester prevent lung injury after hindlimb ischaemia-reperfusion in ventilated rats? Injury 37:380–387.

    PubMed  Article  Google Scholar 

  36. Chen, M. F., P. C. Keng, P. Y. Lin, et al. 2005. Caffeic acid phenethyl ester decreases acute pneumonitis after irradition in vitro and in vivo. BMC Cancer 5:158, Dec 9.

    PubMed  Article  Google Scholar 

  37. Koksel, O., A. Ozdülger, L. Tamer, et al. 2006. Effects of caffeic acid phenethyl ester on lipopolysaccharide induced lung injury in rats. Pulm. Pharmacol. Ther. 19:90–95.

    PubMed  Article  CAS  Google Scholar 

  38. Ates, B., M. I. Doğru, M. Gül, et al. 2006. Protective role of caffeic acid phenethyl ester in the liver of rats exposed to cold stress. Fundam. Clin. Pharmacol. 20:283–289.

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  40. Yılmaz, H. R., E. Uz, N. Yucel, et al. 2004. Protective effect of caffeic acid phenethyl ester on lipid peroxidation and antioxidant enzymes in diabetic rat liver. J. Biochem. Mol. Toxicol. 18:234–238.

    PubMed  Article  Google Scholar 

  41. Kuş, I., N. Colakoğlu, H. Pekmez, et al. 2004. Protective effects of caffeic acid phenethyl ester on carbon tetrachloride-induced hepatotoxicity in rats. Acta Histochem. 106:289–297.

    PubMed  Google Scholar 

  42. Uz, E., F. Öktem, H. R. Yılmaz, et al. 2005. The activities of purine-catabolizing enzymes and the level of nitric oxide in rat kidneys subjected to methotrexate: protective effect of caffeic acid phenethyl ester. Mol. Cell. Biochem. 277:165–170.

    PubMed  Article  CAS  Google Scholar 

  43. Oktem, F., F. Ozguner, O. Sulak, et al. 2005. Lithium-induced renal toxicity in rats: protection by a novel antioxidant caffeic acid phenethyl ester. Mol. Cell. Biochem. 277:109–115.

    PubMed  Article  CAS  Google Scholar 

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Acknowledgement

The authors thank Dr. Fatih Kara for his excellent help in reviewing our statistical analysis.

Author information

Affiliations

  1. Meram Medical Faculty, Department of General Surgery, Selcuk University, Konya, Turkey

    Ahmet Tekin, Tevfik Küçükkartallar & Adil Kartal

  2. Medical Faculty, Department of General Surgery, Akdeniz University, Antalya, Turkey

    Serdar Türkyılmaz

  3. Medical Faculty, Department of General Surgery, Karadeniz Technical University, Trabzon, Turkey

    Ayhan Dinckan

  4. Meram Medical Faculty, Department of Pathology, Selcuk University, Konya, Turkey

    Hasan Esen

  5. Department of Chemistry, Inonu University, Malatya, Turkey

    Burhan Ateş

  6. Department of General Surgery, Private Konya Hospital, Konya, Turkey

    Hüseyin Yılmaz

  7. Feritpaşa mah. Gökhan Sok. Mehmet Katırcı Apt, C Blok. 11/13, 42060, Selçuklu, Konya, Turkey

    Ahmet Tekin

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  1. Ahmet Tekin
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Correspondence to Ahmet Tekin.

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Tekin, A., Küçükkartallar, T., Türkyılmaz, S. et al. Effects of Caffeic Acid Phenethyl Ester (CAPE) on Sepsis in Rats. Inflammation 31, 273–280 (2008). https://doi.org/10.1007/s10753-008-9075-1

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  • DOI: https://doi.org/10.1007/s10753-008-9075-1

KEY WORDS

  • sepsis
  • rats
  • treatment
  • CAPE