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Published in: European Journal of Plastic Surgery 5/2020

01-10-2020 | Experimental Study

Altering effects of caffeic acid phenethyl ester (CAPE) and ischemia/reperfusion injury: an experimental study in a rat TRAM flap model

Authors: Mehmet Emre YEĞİN, Ufuk Bilkay, Yiğit Özer TİFTİKÇİOĞLU, Yiğit Uyanikgil, Türker ÇAVUŞOĞLU, Gülinnaz Ercan, Mehmet Gürdal

Published in: European Journal of Plastic Surgery | Issue 5/2020

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Abstract

Background

Many studies have been performed since the discovery of ischemia-reperfusion injury (I/R) to find substances that reverse its effects on flaps. However, because of minor or major side effects these substances are mostly failed to be put in clinical practice. In this study, the mitigation effects of caffeic acid phenethyl ester (CAPE) were investigated for its protective effects on flap necrosis in a rat model.

Methods

Forty-two randomized male Sprague-Dawley rats weighing between 250 and 300 g were assigned to the regular flap (G1) (n = 14), ischemic flap (G2) (n = 14), and ischemic flap + CAPE (G3) (n = 14) groups. Bilateral pedicled TRAM flaps were designed for the first seven rats of each group,; bilateral-free TRAM flaps were designed for the remaining rats in each group and referred as subgroup 1 and 2 (S1 and S2), respectively. In G1, flaps were returned to their original locations without clamping or injection. In G2 and G3, a 2-h ischemia was performed. Before the ischemic process, intraperitoneal saline and CAPE solution was administered intraperitoneally in the second and third groups, respectively. On day 7 after the operation, all flaps were harvested and subjected to biochemical (malondialdehyde, superoxide dismutase, and catalase levels) and histological examinations (hematoxylin & eosin, Mallory-Azan, anti-VEGF, anti-BAX, anti Bcl-2, and anti-iNOS stainings), respectively. Enzyme levels and the Verhofstadt scores showed a statistically significant difference in flaps among the groups. Less injury was noted in G3 than in G2 (p < 0.01).

Conclusions

In this experimental model, CAPE was effective in protecting tissues against ischemia-reperfusion injury.
Level of evidence: no ratable
Literature
1.
go back to reference Burdock GA (1998) Review of the biological properties and toxicity of bee propolis (propolis). Food Chem Toxicol 36:347–363PubMedCrossRef Burdock GA (1998) Review of the biological properties and toxicity of bee propolis (propolis). Food Chem Toxicol 36:347–363PubMedCrossRef
3.
go back to reference Karaaslan O, Ulusoy MG, Kankaya Y et al (2010) Protective effect of grape seed extract against ischaemia/reperfusion injury in a rat epigastric flap model. J Plast Reconstr Aesthet Surg 63:705–710PubMedCrossRef Karaaslan O, Ulusoy MG, Kankaya Y et al (2010) Protective effect of grape seed extract against ischaemia/reperfusion injury in a rat epigastric flap model. J Plast Reconstr Aesthet Surg 63:705–710PubMedCrossRef
4.
go back to reference Tolba MF, Azab SS, Khalifa AE, Abdel-Rahman SZ, Abdel-Naim AB (2013) Caffeic acid phenethyl ester, a promising component of propolis with a plethora of biological activities: a review on its anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective effects. IUBMB Life 65:699–709PubMedCrossRef Tolba MF, Azab SS, Khalifa AE, Abdel-Rahman SZ, Abdel-Naim AB (2013) Caffeic acid phenethyl ester, a promising component of propolis with a plethora of biological activities: a review on its anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective effects. IUBMB Life 65:699–709PubMedCrossRef
5.
go back to reference Aydogan H, Gurlek A, Parlakpinar H et al (2007) Beneficial effects of caffeic acid phenethyl ester (CAPE) on the ischaemia-reperfusion injury in rat skin flaps. J Plast Reconstr Aesthet Surg 60:563–568PubMedCrossRef Aydogan H, Gurlek A, Parlakpinar H et al (2007) Beneficial effects of caffeic acid phenethyl ester (CAPE) on the ischaemia-reperfusion injury in rat skin flaps. J Plast Reconstr Aesthet Surg 60:563–568PubMedCrossRef
6.
go back to reference Okşar HS, Coşkunfιrat OK, Özgentaş HE (2001) Perforator-based flap in rats: a new experimental model. Plast Reconstr Surg 108:125–131PubMedCrossRef Okşar HS, Coşkunfιrat OK, Özgentaş HE (2001) Perforator-based flap in rats: a new experimental model. Plast Reconstr Surg 108:125–131PubMedCrossRef
7.
go back to reference Aslan C, Melikoglu C, Ocal I, Saglam G, Sutcu R, Hosnuter M (2014) Effect of epigallocatechin gallate on ischemia-reperfusion injury: an experimental study in a rat epigastric island flap. Int J Clin Exp Med 7:57–66PubMedPubMedCentral Aslan C, Melikoglu C, Ocal I, Saglam G, Sutcu R, Hosnuter M (2014) Effect of epigallocatechin gallate on ischemia-reperfusion injury: an experimental study in a rat epigastric island flap. Int J Clin Exp Med 7:57–66PubMedPubMedCentral
8.
go back to reference Ozyurt H, Ozyurt B, Koca K, Ozgocmen S (2007) Caffeic acid phenethyl ester (CAPE) protects rat skeletal muscle against ischemia-reperfusion-induced oxidative stress. Vasc Pharmacol 47:108–112CrossRef Ozyurt H, Ozyurt B, Koca K, Ozgocmen S (2007) Caffeic acid phenethyl ester (CAPE) protects rat skeletal muscle against ischemia-reperfusion-induced oxidative stress. Vasc Pharmacol 47:108–112CrossRef
9.
go back to reference Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedCrossRef Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedCrossRef
12.
go back to reference Kıyan S, Uyanıkgil Y, Ali Altuncı Y, Çavuşoğlu T, Uyanıkgil EÖÇ, Karabey F (2015) Deneysel haşlama tipi yanıklarda Hypericum perforatum (Kantaron) tedavisinin akut etkilerinin araştırılması ve gümüş sülfadiazin tedavisiyle karşılaştırılması. Ulus Travma ve Acil Cerrahi Derg 21:323–336 Kıyan S, Uyanıkgil Y, Ali Altuncı Y, Çavuşoğlu T, Uyanıkgil EÖÇ, Karabey F (2015) Deneysel haşlama tipi yanıklarda Hypericum perforatum (Kantaron) tedavisinin akut etkilerinin araştırılması ve gümüş sülfadiazin tedavisiyle karşılaştırılması. Ulus Travma ve Acil Cerrahi Derg 21:323–336
13.
go back to reference Hearse DJ (1990) Ischemia, reperfusion and the determinants of tissue injury. Cardiovasc Drugs Ther 4:767–776PubMedCrossRef Hearse DJ (1990) Ischemia, reperfusion and the determinants of tissue injury. Cardiovasc Drugs Ther 4:767–776PubMedCrossRef
14.
go back to reference Ozyurt B, Iraz M, Koca K, Ozyurt H, Sahin S (2006) Protective effects of caffeic acid phenethyl ester on skeletal muscle ischemia-reperfusion injury in rats. Mol Cell Biochem 292:197–203PubMedCrossRef Ozyurt B, Iraz M, Koca K, Ozyurt H, Sahin S (2006) Protective effects of caffeic acid phenethyl ester on skeletal muscle ischemia-reperfusion injury in rats. Mol Cell Biochem 292:197–203PubMedCrossRef
15.
go back to reference Pang CY, Forrest CR, Mounsey R (1993) Pharmacologic intervention in ischemia-induced reperfusion injury in the skeletal muscle. Microsurgery 14:176–182PubMedCrossRef Pang CY, Forrest CR, Mounsey R (1993) Pharmacologic intervention in ischemia-induced reperfusion injury in the skeletal muscle. Microsurgery 14:176–182PubMedCrossRef
16.
go back to reference Angel MF, Haddad J, Abramson J (1987) A free radical scavenger reduces hematoma-induced flap necrosis in Fischer rats. Otolaryngol Head Neck Surg 96:96–98PubMedCrossRef Angel MF, Haddad J, Abramson J (1987) A free radical scavenger reduces hematoma-induced flap necrosis in Fischer rats. Otolaryngol Head Neck Surg 96:96–98PubMedCrossRef
17.
go back to reference Latifoğlu O, Atabay K, Çelebi C et al (1995) Nikotin etkisi altındaki deri fleplerinin yaşayan uzunluğuna nifedipinin etkisinin araştırılması. Türk Plastik Cerrahi Dergisi 3:144–151 Latifoğlu O, Atabay K, Çelebi C et al (1995) Nikotin etkisi altındaki deri fleplerinin yaşayan uzunluğuna nifedipinin etkisinin araştırılması. Türk Plastik Cerrahi Dergisi 3:144–151
18.
go back to reference Zaccaria A, Weinzweig N, Yoshitake M et al (1994) Vitamin C reduces ischemia–reperfusion injury in rat epigastric island skin flap model. Ann Plast Surg 33:620–623PubMedCrossRef Zaccaria A, Weinzweig N, Yoshitake M et al (1994) Vitamin C reduces ischemia–reperfusion injury in rat epigastric island skin flap model. Ann Plast Surg 33:620–623PubMedCrossRef
19.
go back to reference Carroll SM, Overgoor ML, Tobin G et al (1997) Acute ischemic preconditioning of skeletal muscle prior to flap elevation augments muscle-flap survival. Plast Reconstr Surg 100:58–65PubMedCrossRef Carroll SM, Overgoor ML, Tobin G et al (1997) Acute ischemic preconditioning of skeletal muscle prior to flap elevation augments muscle-flap survival. Plast Reconstr Surg 100:58–65PubMedCrossRef
20.
go back to reference Du Q, Hao C, Gou J et al (2016) Protective effects of p-nitro caffeic acid phenethyl ester on acute myocardial ischemia-reperfusion injury in rats. Exp Ther Med 11:1433–1440PubMedPubMedCentralCrossRef Du Q, Hao C, Gou J et al (2016) Protective effects of p-nitro caffeic acid phenethyl ester on acute myocardial ischemia-reperfusion injury in rats. Exp Ther Med 11:1433–1440PubMedPubMedCentralCrossRef
21.
go back to reference Yazgan UC, Elbey B, Kus S et al (2017) Effect of caffeic acid phenethyl ester on oxidant and antioxidant status of liver and serum in a rat model with acute methanol intoxication. Ir J Med Sci 186:519–523PubMedCrossRef Yazgan UC, Elbey B, Kus S et al (2017) Effect of caffeic acid phenethyl ester on oxidant and antioxidant status of liver and serum in a rat model with acute methanol intoxication. Ir J Med Sci 186:519–523PubMedCrossRef
22.
go back to reference Ozturk G, Ginis Z, Akyol S, Erden G, Gurel A, Akyol O (2012) The anticancer mechanism of caffeic acid phenethyl ester (CAPE): review of melanomas, lung and prostate cancers. Eur Rev Med Pharmacol Sci 16:2064–2068PubMed Ozturk G, Ginis Z, Akyol S, Erden G, Gurel A, Akyol O (2012) The anticancer mechanism of caffeic acid phenethyl ester (CAPE): review of melanomas, lung and prostate cancers. Eur Rev Med Pharmacol Sci 16:2064–2068PubMed
23.
go back to reference Bellows SD, Hale SL, Kloner RA (1996) Acute ethanol does not protect against ischemic/reperfusion injury in rabbit myocardium. J Thromb Thrombolysis 3(3):181–184PubMedCrossRef Bellows SD, Hale SL, Kloner RA (1996) Acute ethanol does not protect against ischemic/reperfusion injury in rabbit myocardium. J Thromb Thrombolysis 3(3):181–184PubMedCrossRef
24.
go back to reference Sarifakioglu N, Gokrem S, Ates L, Akbuga UB, Aslan G (2004) The influence of sildenafil on random skin flap survival in rats: an experimental study. Br J Plast Surg 57:769–772PubMedCrossRef Sarifakioglu N, Gokrem S, Ates L, Akbuga UB, Aslan G (2004) The influence of sildenafil on random skin flap survival in rats: an experimental study. Br J Plast Surg 57:769–772PubMedCrossRef
25.
go back to reference Kayiran O, Cuzdan SS, Uysal A, Kocer U (2013) Tadalafil significantly reduces ischemia reperfusion injury in skin island flaps. Indian J Plast Surg 46:75–81PubMedPubMedCentralCrossRef Kayiran O, Cuzdan SS, Uysal A, Kocer U (2013) Tadalafil significantly reduces ischemia reperfusion injury in skin island flaps. Indian J Plast Surg 46:75–81PubMedPubMedCentralCrossRef
26.
go back to reference Ersoy B, Çevik Ö, Çilingir ÖT (2016) Etanercept protects myocutaneous flaps from ischaemia reperfusion injury: an experimental study in a rat tram flap model. J Plast Surg Hand Surg 50:208–215PubMedCrossRef Ersoy B, Çevik Ö, Çilingir ÖT (2016) Etanercept protects myocutaneous flaps from ischaemia reperfusion injury: an experimental study in a rat tram flap model. J Plast Surg Hand Surg 50:208–215PubMedCrossRef
27.
go back to reference Ocak S, Gorur S, Hakverdi S, Celik S, Erdogan S (2007) Protective effects of caffeic acid phenethyl ester, vitamin C, vitamin E and N-acetylcysteine on vancomycin-induced nephrotoxicity in rats. Basic Clin Pharmacol Toxicol 100:328–333PubMedCrossRef Ocak S, Gorur S, Hakverdi S, Celik S, Erdogan S (2007) Protective effects of caffeic acid phenethyl ester, vitamin C, vitamin E and N-acetylcysteine on vancomycin-induced nephrotoxicity in rats. Basic Clin Pharmacol Toxicol 100:328–333PubMedCrossRef
28.
go back to reference Lee YK, Nata’atmaja BS, Kim BH et al (2017) Protective effect of telomerase-based 16-mer peptide vaccine (GV1001) on inferior epigastric island skin flap survivability in ischaemia-reperfusion injury rat model. J Plast Surg Hand Surg 51:210–216PubMedCrossRef Lee YK, Nata’atmaja BS, Kim BH et al (2017) Protective effect of telomerase-based 16-mer peptide vaccine (GV1001) on inferior epigastric island skin flap survivability in ischaemia-reperfusion injury rat model. J Plast Surg Hand Surg 51:210–216PubMedCrossRef
29.
go back to reference Zhang P, Tang Y, Li N-G, Zhu Y, Duan JA (2014) Bioactivity and chemical synthesis of caffeic acid phenethyl ester and its derivatives. Molecules 19:16458–16476PubMedPubMedCentralCrossRef Zhang P, Tang Y, Li N-G, Zhu Y, Duan JA (2014) Bioactivity and chemical synthesis of caffeic acid phenethyl ester and its derivatives. Molecules 19:16458–16476PubMedPubMedCentralCrossRef
Metadata
Title
Altering effects of caffeic acid phenethyl ester (CAPE) and ischemia/reperfusion injury: an experimental study in a rat TRAM flap model
Authors
Mehmet Emre YEĞİN
Ufuk Bilkay
Yiğit Özer TİFTİKÇİOĞLU
Yiğit Uyanikgil
Türker ÇAVUŞOĞLU
Gülinnaz Ercan
Mehmet Gürdal
Publication date
01-10-2020
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Plastic Surgery / Issue 5/2020
Print ISSN: 0930-343X
Electronic ISSN: 1435-0130
DOI
https://doi.org/10.1007/s00238-020-01637-9

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