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Effects of Caffeic Acid Phenethyl Ester and Oxidative Stress Caused by the Exhaustion Exercise on Endotelial Damage

M. Akil


This study was aimed to examine the effects of caffeic acid phenethyl ester (CAPE) on endothelial dysfunction in rats with exercise-induced oxidative stress. Tests were performed on male (n=32) young adult Sprague-Dawley rats (12 weeks of age). The experimental animals were divided into four groups in equal numbers. Group 1: General control group; Group 2: Swimming control group. Group 3: CAPE supplemented general control group. Group 4: CAPE supplemented swimming group. Furthermore, animals used in the experiment were made to do exhaustion practice toward the end of the examination. Plasma and liver tissue asymmetric dimethylarginine (ADMA) concentrations were not significantly (p<0.05) increased in rats with acute swimming exercise compared to controls. Blood and liver cytokines levels were expanded in comparison to control group and CAPE groups (p<0.05). Total antioxidant status (TAS) levels in acute swimming exercise groups reduced compared to the control group. Besides, total oxidant status (TOS) levels were considerably elevated compared to the control and CAPE groups. In this study, acute swimming exercise induced that oxidative stress could cause early onset of endothelial damage. Besides, CAPE can demonstrate protective effects on endothelial damage, inflammation and oxidative stress axis.


Endotel Damage, ADMA, Oxidative Stress, Exercise

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Akil M., Biçer M., Kiliç M., Avunduk M.C., Moğulkoç R., Baltaci A.K. Effect of intraperitoneal selenium administration on liver glycogen levels in rats subjected to acute forced swimming. Biological Trace Element Research, 139(3): 341-346, 2011.

Akil M., Çoban F.K., Yalçinkaya Ö. The effect of caffeic acid phenethyl ester cape fortification on the liver element distribution that occurs after exercise. Biological Trace Element Research, 172: 419-423, 2016.

Akil M., Gurbuz Ü., Biçer M., Sivrikaya A., Moğulkoç R., Baltaci A.K. Effect of selenium supplementation on lipid peroxidation, antioxidant enzymes, and lactate levels in rats immediately after acute swimming exercise. Biol Trace Elem Res, 142: 651-659, 2011.

Akil M., Gürbüz U., Biçer M., Halifeoğlu İ., Baltaci A.K., Mogulkoç R. Selenium prevents lipid peroxidation in liver and lung tissues of rats in acute swimming exercise. Bratislava Medical Journal-Bratislavske Lekarske Listy, 116(4): 233-235, 2015.

Akyol S., Ozturk G., Ginis Z., Armutcu F., Yigitoglu M.R., Akyol O. In vivo and in vitro antineoplastic actions of caffeic acid phenethyl ester (CAPE): Therapeutic perspectives. Nutr Cancer, 65: 515 526, 2013.

Aruoma O.I. Free radicals and antioxidant strategies in sports. J Nutr Biochem, 5: 370-381, 1994.

Asagami T., Abbasi F., Stuelinger M., Lamendola C., McLaughlin T., Cooke J.P., Reaven G.M., Tsao P.S. Metformin treatment lowers asymmetric dimethylarginine concentrations in patients with type 2 diabetes. Metabolism, 51: 843-846, 2002.

Balon T.W., Nadler J.L. Nitric oxide release is present from incubated skeletal muscle preparations. J Appl Physiol, 77: 2519-2521, 1994.

Biçer M., Akil M., Baltaci A.K., Moğulkoç R., Sivrikaya A., Akkuş H. Effect of melatonin on element distribution in the liver tissue of diabetic rats subjected to forced exercise. Bratislava Medical Journal, 116(2): 119-123, 2015.

Biçer M., Akil M., Baltaci A.K., Moğulkoç R., Sivrikaya A., Günay M., Akkuş H. Protective effect of melatonin on lipid peroxidation in various tissues of diabetic rats subjected to an acute swimming exercise. Bratislava Medical Journal, 113(12): 698-701. 2012.

Biçer M., Akil M.,Sivrikaya A., Kara E., Baltaci A.K., Moğulkoç R. Effect of zinc supplementation on the distribution of various elements in the serum of diabetic rats subjected to an acute swimming exercise. Journal of Physiology and Biochemistry, 67(4): 511-517, 2011.

Biçer M., Günay M., Akil M., Avunduk M.C., Moğulkoç R., Baltaci A.K. Effect of long term intraperitoneal zinc administration on liver glycogen levels in diabetic rats subjected to acute forced swimming. Biological Trace Element Research, 139(3): 317-324, 2011.

Böger R.H., Bode-Böger S.M., Szuba A., Tsao P.S., Chan J.R., Tangphao O., Blaschke T.F., Cooke J.P. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation, 98: 1842-1847, 1998.

Böger R.H., Bode-Böger S.M., Tsao P.S., Lin P.S., Chan J.R., Cooke J.P. An endogenous inhibitor of nitric oxide synthase regulates endothelial adhesiveness for monocytes. J Am Coll Cardiol, 36: 2287-2295, 2000.

Böger R.H., Sydow K., Borlak J., Thum T., Lenzen H., Schubert B., Tsikas D., Bode-Böger S.M. LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases. Circ Res. 87: 99-105, 2000.

Bradford M.M. A rapid and sensitive method for the quantita-tion of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry. 7(72): 248-254, 1976.

Cai H., Harrison D.G. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circulation Research, 87: 840-4, 2000.

Cooke J.P. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol, 20: 2032-7, 2000.

Davies K.J., Quintanilha A.T., Brooks G.A., Packer L. Free radicals and tissue damage produced by exercise. Biochem Biophys Res- Commun, 107(4): 1198-205, 1982.

Dawson C.A., Horvarth S.M. Swimming in small laboratory animals. Medicine and Science in Sports, 2: 51-78. 1970.

Dikalova A.E., Bikineyeva A.T., Budzyn K., Nazarewicz R.R., McCann L., Lewis W., Harrison D.G., Dikalov S.I. Therapeutic targeting of mitochondrial superoxide in hypertension. Circ Res, 107(1): 106-16, 2010.

Dillard C.J., Litov R.E., Savin W.M., Dumelin E.E., Tappel A.L. Effects of exercise, vitamin E, and ozone on pulmonary function and lipid peroxtionidation. J Appl Physiol., 45(6): 927-32, 1978.

Dymkowska D., Drabarek B., Podszywalow-Bartnicka P., Szczepanowska J., Zablocki K. Hyperglycaemia modifies energy metabolism and reactive oxygen species formation in endothelial cells in vitro. Arch Biochem Biophys, 542: 7-13, 2014.

Heitzer T., Ylä Herttuala S., Wild E., Luoma J., Drexler H. Effect of vitamin E on endothelial vasodilator function in patients with hypercholesterolemia, chronic smoking or both. J Am Coll Cardiol, 33: 499-505, 1999.

Hermenegildo C., Medina P., Peiró M., Segarra G., Vila J.M., Ortega J., Lluch S. Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in hyperthyroid patients. J Clin Endocrinol Metab, 87: 5636-5640, 2002.

Karabag-Coban F., Akil M., Liman R., Cigerci İ.H. Antioxidant and genotoxic effects of caffeic acid phenethyl ester (cape) in exercise-induced oxidative stress. Fresenius Environmental Bulletin, 26(4): 2684-2688, 2017.

Karabag-Coban F., Akil M., Liman R., Ciğerci İ.H. Effects of resveratrol on oxidative dna damage induced by the acute swimming exercise. Journal of Pharmaceutical Research International, 21(4): 1-10, 2018.

Leiper J., Murray-Rust J., McDonald N., Vallance P. S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Proc Natl Acad Sci USA, 99: 13527-32, 2002.

Lin K.Y., Ito A., Asagami T., Tsao P.S., Adimoolam S., Kimoto M., Tsuji H., Reaven G.M., Cooke J.P. Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation, 106: 987-92, 2002.

Martarelli D., Cocchioni M., Scuri S., Spataro A., Pompei P. Cold exposure increases exercise- induced oxidative stress. J Sports Med Phys Fitnesss, 51: 299-304, 2011.

Münzel T., Gori T., Bruno R.M., Taddei S. Is oxidative stress a therapeutic target in cardiovascular disease? European Heart Journal, 31: 2741-8, 2010.

Natarajan K., Singh S., Burke T.R., Jr Grunberger D., Aggarwal B.B. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF kappa B. Proc Natl Acad Sci USA, 93: 9090 9095, 1996.

Palmer R.M., Ferrige A.G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature, 327: 524-6. 1987.

Radomski MW, Palmer RM, Moncada S. The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol. 1987; 92: 639-46.

Rhoads, R.P., Baumgard L.H., Suagee J.K., Sanders S.R. Nutritional interventions to alleviate the negative consequences of heat stress. Adv Nutr. 4: 267-276, 2013.

Sessa W.C. The nitric oxide synthase family of proteins. J Vasc Res, 31: 131-143, 1994.

Sivrikaya A., Biçer M., Akil M., Baltaci A.K., Moğulkoç R. Effects of Zinc Supplementation on the Element Distribution in Kidney Tissue of Diabetic Rats Subjected to Acute Swimming. Biological Trace Element Research, 147(1-3): 195-199, 2012.

Sud'ina G.F., Mirzoeva O.K., Pushkareva M.A., Korshunova G.A., Sumbatyan N.V., Varfolomeev S.D. Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS Lett, 329: 21 24, 1993.

Suwaidi J.A., Hamasaki S., Higano S.T., Nishimura D.R., Holmes Jr D.R., Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation, 101: 948-54, 2000.

Sydow K., Schwedhelm E., Arakawa N., Bode-Böger S.M., Tsikas D., Hornig B., Frölich J.C., Böger R.H. ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst (e) inemia: effects of l-arginine and B vitamins. Cardiovasc Res, 57: 244-52, 2003.

Touyz R.M., Montezano A.C. Vascular Nox4: a multifarious NADPH oxidase. Circ Res, 110(9): 1159-61, 2012.

Tripepi G., Mattace Raso F., Sijbrands E., Seck M.S., Maas R., Boger R., Witteman J., Rapisarda F., Malatino L., Mallamaci F., Zoccali C. Inflammation and asymmetric dimethylarginine for predicting death and cardiovascular events in ESRD patients. Clin J Am So Nephrol, 6: 1714-1721, 2011.

Usui M., Matsuoka H., Miyazaki H., Ueda S., Okuda S., Imaizumi T. Increased endogenous nitric oxide synthase inhibitor in patients with congestive heart failure. Life Sci, 62: 2425-2430, 1998.

Valkonen V.P., Tuomainen T.P., Laaksonen R. DDAH gene and cardiovascular risk. Vasc Med,; 10: 45-8, 2005.

Virdis A., Bacca A., Colucci R., Duranti E., Fornai M., Materazzi G., Ippolito C., Bernardini N., Blandizzi C., Bernini G., Taddei S. Endothelial dysfunction in small arteries of essential hypertensive patients: role of cyclooxygenase-2 in oxidative stress generation. Hypertension, 62: 337-44, 2013.



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