Author for correspondence: Abdurrauf Yüce, Department of Physiology, Faculty of Veterinary Medicine, Fırat University, 23119 Elazıg, Turkey (fax +90 424 238 81 73, e-mail [email protected]).

This work was conducted at the Experimental Research Centre, Fırat University Medical School, Elazıg, Turkey.

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Abstract

Abstract: Treatment with cyclosporine A has significantly improved long-term survival after organ transplantations. Cyclosporine A also causes a dose-related decrease in body functions in experimental animals and human beings. The generation of reactive oxygen species has been implicated in cyclosporine A-induced dysfunctions. The aim of this study was to determine the effects of ellagic acid on cyclosporine A-induced alterations in the kidney, liver and heart oxidant/antioxidant system. The control group was treated with placebo and subcutaneous injection of 0.5 ml isotonic saline + 0.5 ml slightly alkaline solution for 21 days. The cyclosporine A group received a subcutaneous injection of cyclosporine A (15 mg/kg) + 0.5 ml slightly alkaline solution for 21 days. The ellagic acid group was treated with a subcutaneous injection of 0.5 ml isotonic saline + ellagic acid (10 mg/kg) for 21 days. The cyclosporine A plus ellagic acid group received a subcutaneous injection of cyclosporine A + ellagic acid for 21 days. Ellagic acid and slightly alkaline solution were administered by gavage. The rats were killed at the end of the treatment period. Malondialdehyde (MDA) and reduced glutathione (GSH) levels, glutathione peroxidase (GSH-Px) and catalase (CAT) activities were determined in kidney, liver and heart tissues. While administration of cyclosporine A increased the MDA levels in kidney, liver and heart tissues, it decreased the GSH, GSH-Px and CAT in these samples when compared to the control group. However, the simultaneously administration of ellagic acid markedly normalized the cyclosporine A-induced liver and heart MDA levels, liver CAT activities and GSH-Px activities of all samples. Cyclosporine A caused marked damages in the histopathological status of kidney, liver and heart tissues, which were partially ameliorated by ellagic acid administration. In conclusion, ellagic acid may be used in combination with cyclosporine A in transplantation treatment to improve the cyclosporine A-induced oxidative stress parameters and other adverse effects.

References

1 Ponticelli C. Cyclosporine: from renal transplantation to autoimmune diseases. Ann N Y Acad Sci 2005; 1051: 551–8.
10.1196/annals.1361.099
CAS Google Scholar
2 Ateşşahin A, Çeribaşı AO, Yılmaz S. Lycopene, a carotenoid, attenuates cyclosporine-induced renal dysfunction and oxidative stress in rats. Basic Clin Pharmacol Toxicol 2007; 100: 372–6.
10.1111/j.1742-7843.2007.00060.x
PubMed Web of Science® Google Scholar
3 Bianchi R, Rodella L, Rezzani R. Cyclosporine A up-regulates expression of matrix matalloproteinase 2 and vascular endotelial growth factor in rat heart. Int Immunopharmacol 2003; 3: 427–33.
CAS PubMed Web of Science® Google Scholar
4 Rezzani R. Cyclosporine A and adverse effects on organs: histochemical studies. Prog Histochem Cytochem 2004; 39: 85–128.
10.1016/j.proghi.2004.04.001
CAS PubMed Web of Science® Google Scholar
5 Abuja PM, Albertini R. Methods for monitoring oxidative stress, lipid peroxidation and oxidation resistance of lipoproteins. Clin Chim Acta 2001; 306: 1–17.
10.1016/S0009-8981(01)00393-X
CAS PubMed Web of Science® Google Scholar
6 Akyol O, Herken H, Uz E, Fadillioǧlu E, Unal S, Söǧüt S et al . The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. The possible role of oxidant/antioxidant imbalance. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26: 995–1005.
10.1016/S0278-5846(02)00220-8
CAS PubMed Web of Science® Google Scholar
7 Soong YY, Barlow PJ. Antioxidant activity and phenolic content of selected fruit seeds. Food Chem 2004; 88: 411–7.
10.1016/j.foodchem.2004.02.003
CAS Web of Science® Google Scholar
8 Soong YY, Barlow PJ. Quantification of gallic acid and ellagic acid from longan (Dimocarpus longan Lour.) seed and mango (Mangifera indica L.) kernel and their effects on antioxidant activity. Food Chem 2006; 97: 524–30.
10.1016/j.foodchem.2005.05.033
CAS Web of Science® Google Scholar
9 Wang RF, Xie WD, Zhang Z, Xing DM, Ding Y, Wang W et al . Bioactive compounds from the seeds of punica granatum (pomegranate). J Nat Prod 2004; 67: 2096–8.
10.1021/np0498051
CAS PubMed Web of Science® Google Scholar
10 Hassoun EA, Walter AC, Alsharif NZ, Stohs SJ. Modulation of TCDD-induced fetotoxicity and oxidative stress in embriyonic and placental tissues of C57BL/6J mice by vitamin E succinate and ellagic acid. Toxicology 1997; 124: 27–37.
10.1016/S0300-483X(97)00127-3
CAS PubMed Web of Science® Google Scholar
11 Hassoun EA, Vodhanel J, Abushaban A. The modulatory effects of ellagic acid and vitamin E succinate on TCDD-induced oxidative stress in different brain regions of rats after subchronic exposure. J Biochem Mol Toxicol 2004; 18: 196–203.
10.1002/jbt.20030
CAS PubMed Web of Science® Google Scholar
12 Whitley AC, Stoner GD, Darby MV, Walle T. Intestinal epithelial cell accumulation of the cancer preventive polyphenol ellagic acid-extensive binding to protein and DNA. Biochem Pharmacol 2003; 66: 907–15.
10.1016/S0006-2952(03)00413-1
CAS PubMed Web of Science® Google Scholar
13 Loarca-Piña G, Kuzmicky PA, De Mejia EG, Kado NY. Inhibitory effects of ellagic acid on the direct-acting mutagenicity of aflatoxin B₁ in the Salmonella microsuspension assay. Mutat Res 1998; 398: 183–7.
10.1016/S0027-5107(97)00245-5
CAS PubMed Web of Science® Google Scholar
14 Priyadarsini KI, Khopde SM, Kumar SS, Mohan H. Free radical studies of ellagic acid, natural phenolic antioxidants. J Agric Food Chem 2002; 50: 2200–6.
10.1021/jf011275g
CAS PubMed Web of Science® Google Scholar
15 Rezzani R, Buffoli B, Rodella L, Stacchiotti A, Bianchi R. Protective role of melatonin in cyclosporine A-induced oxidative stress in rat liver. Int Immunopharmacol 2005; 5: 1397–405.
10.1016/j.intimp.2005.03.021
CAS PubMed Web of Science® Google Scholar
16 Chung BH, Li C, Sun BK, Lim SW, Ahn KO, Yang JH et al . Rosiglitazone protects against cyclosporine-induced pancreatic and renal injury in rats. Am J Transplant 2005; 5: 1856–67.
10.1111/j.1600-6143.2005.00979.x
CAS PubMed Web of Science® Google Scholar
17 Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem 1966; 16: 359–64.
10.1016/0003-2697(66)90167-9
CAS PubMed Web of Science® Google Scholar
18 Sönmez M, Türk G, Yüce A. The effect of ascorbic acid supplementation on sperm quality, lipid peroxidation and testosterone levels of male Wistar rats. Theriogenology 2005; 63: 2063–72.
10.1016/j.theriogenology.2004.10.003
CAS PubMed Web of Science® Google Scholar
19 Yüce A, Ateşşahin A, Çeribaşı AO, Aksakal M. Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissues of rats. Basic Clin Pharmacol Toxicol 2007; 101: 345–9.
10.1111/j.1742-7843.2007.00129.x
CAS PubMed Web of Science® Google Scholar
20 Aebi H. Catalase. In: HU Bergmeyer (ed.). In Methods of Enzymatic Analysis. Academic Press, New York, 1974; 673–7.
10.1016/B978-0-12-091302-2.50032-3
Google Scholar
21 Lawrence RA, Burk RF. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 1976; 71: 952–8.
10.1016/0006-291X(76)90747-6
CAS PubMed Web of Science® Google Scholar
22 Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem 1968; 25: 192–205.
10.1016/0003-2697(68)90092-4
CAS PubMed Web of Science® Google Scholar
23 Lowry OH, Rosebrough NJ, Farr AL, Randall RI. Protein measurement with folin phenol reagent. J Biol Chem 1951; 193: 265–75.
10.1016/S0021-9258(19)52451-6
CAS PubMed Web of Science® Google Scholar
24 Bancroft JD, Stevens A. Theory and Practice of Histological Techniques, 3rd edn. Churchill Livingstone, London, 1990.
Google Scholar
25 Kahan BD. Cyclosporine. N Engl J Med 1989; 321: 1725–38.
10.1056/NEJM198912213212507
CAS PubMed Web of Science® Google Scholar
26 Türk G, Ateşşahin A, Sönmez M, Yüce A, Ceribaşi AO. Lycopene protects against cyclosporine A-induced testicular toxicity in rats. Theriogenology 2007; 67: 778–85.
10.1016/j.theriogenology.2006.10.013
CAS PubMed Web of Science® Google Scholar
27 Amudha G, Josephine A, Varalakshmi P. Role of lipoic acid in reducing the oxidative stress induced by cyclosporine A. Clin Chim Acta 2006; 372: 134–9.
10.1016/j.cca.2006.03.036
CAS PubMed Web of Science® Google Scholar
28 Hagar HH. The protective effect of taurine against cyclosporine A-induced oxidative stress and hepatotoxicity in rats. Toxicol Lett 2004; 151: 335–43.
10.1016/j.toxlet.2004.03.002
CAS PubMed Web of Science® Google Scholar
29 Rezzani R, Giugno L, Buffoli B, Bonomini F, Bianchi R. The protective effect of caffeic acid phenethyl ester against cyclosporine A-induced cardiotoxicity in rats. Toxicology 2005; 212: 155–64.
10.1016/j.tox.2005.04.020
CAS PubMed Web of Science® Google Scholar
30 Packer L, Landvik S. Vitamin E in biological systems. In: I Emerit, L Packer, C Auclair (eds). Antioxidants in Therapy and Preventive Medicine. Plenum Press, New York, 1990; 93–104.
10.1007/978-1-4684-5730-8_13
Web of Science® Google Scholar
31 Conklin KA. Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects. Nutr Cancer 2000; 37: 1–18.
10.1207/S15327914NC3701_1
CAS PubMed Web of Science® Google Scholar
32 Mohamadin AM, El-Beshbishy HA, El-Mahdy MA. Green tea extract attenuates cyclosporine A-induced oxidative stress in rats. Pharmacol Res 2005; 51: 51–7.
10.1016/j.phrs.2004.04.007
CAS PubMed Web of Science® Google Scholar
33 Khanduja KL, Gandhi RK, Pathania V, Syal N. Prevention of N-Nitrosodiethylamine-induced lung tumorigenesis by ellagic acid and quercetin in mice. Food Chem Toxicol 1999; 37: 313–8.
10.1016/S0278-6915(99)00021-6
CAS PubMed Web of Science® Google Scholar
34 Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG et al . In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem 2005; 16: 360–7.
10.1016/j.jnutbio.2005.01.006
CAS PubMed Web of Science® Google Scholar
35 Amudha G, Josephine A, Sudhahar V, Varalakshmi P. Protective effect of lipoic acid on oxidative and peroxidative damage in cyclosporine A-induced renal toxicity. Int Immunopharmacol 2007; 7: 1442–9.
10.1016/j.intimp.2007.06.010
CAS PubMed Web of Science® Google Scholar
36 Selcoki Y, Uz E, Bayrak R, Sahin S, Kaya A, Uz B et al . The protective effect of erdosteine against cyclosporine A-induced cardiotoxicity in rats. Toxicology 2007; 239: 53–9.
10.1016/j.tox.2007.06.096
CAS PubMed Web of Science® Google Scholar
37 Brown JE, Khodr H, Hider RC, Rice-Evans CA. Structural dependence of flavonoid interactions with Cu²⁺ Ions: implications for their antioxidant properties. Biochem J 1998; 330: 1173–8.
10.1042/bj3301173
CAS PubMed Web of Science® Google Scholar
38 Singh K, Khanna AK, Visen PKS, Chander R. Protective effect of ellagic acid on t-butyl hydroperoxide induced lipid peroxidation in isolated hepatocytes. Indian J Exp Biol 1999; 37: 939–40.
CAS PubMed Google Scholar

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Amelioration of Cyclosporine A-Induced Renal, Hepatic and Cardiac Damages by Ellagic Acid in Rats*

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Amelioration of Cyclosporine A-Induced Renal, Hepatic and Cardiac Damages by Ellagic Acid in Rats*

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