Exp Clin Endocrinol Diabetes 2007; 115(6): 365-371
DOI: 10.1055/s-2007-971056
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Protective Effects of Chronic Melatonin Treatment Against Renal Ischemia/Reperfusion Injury in Streptozotocin-Induced Diabetic Rats

Z. Kurcer 1 , H. Parlakpinar 2 , N. Vardi 3 , S. Tasdemir 2 , M. Iraz 2 , E. Fadillioglu 4 , F. Baba 5 , M. Gül 3
  • 1Department of Pharmacology, Faculty of Medicine, Harran University, Sanliurfa, Turkey
  • 2Department of Pharmacology, Faculty of Medicine, Inonu University, Malatya, Turkey
  • 3Department of Histology and Embriology, Faculty of Medicine, Inonu University, Malatya, Turkey
  • 4Department of Physiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
  • 5Department of Phathology, Faculty of Medicine, Harran University, Sanliurfa, Turkey
Further Information

Publication History

received 10. 9. 2006 first decision 1. 2. 2007

accepted 1. 2. 2007

Publication Date:
08 June 2007 (online)

Abstract

Aims: The purpose of this study was to investigate the effects of chronic administration of melatonin on renal ischemia/reperfusion (IR) injury in streptozotocin (STZ)-induced diabetic rats.

Methodology: Male Sprague-Dawley rats were divided into six groups: control (C), diabetes mellitus (DM), control+IR (C+IR), DM+IR, Melatonin+IR (Mel+IR), DM+Mel+IR. Diabetic and non-diabetic rats were given melatonin 4 mg/kg/day, i.p., for 15 days. The left renal artery and vein of rats were occluded for 30 min at the 18th day, followed by 24 h of reperfusion.

Results: In comparison with control group, the levels of malondialdehyde (MDA), protein carbonyl (PC) and and nitric oxide (NO) were determined to be higher in the renal homogenates of DM, DM+IR and C+IR groups. MDA and NO levels were found to be similar in the DM+melatonin+IR and control groups. The most significant histological damage was found in the DM+IR group and this damage was significantly reduced by melatonin.

Conclusion: Chronic melatonin treatment reduces renal injury by reducing lipid oxidation and NO production in STZ-induced diabetic rats exposed to IR.

References

  • 1 Aksoy N, Vural H, Sabuncu T, Aksoy S. Effects of melatonin on oxidative-antioxidative status of tissues in streptozotocine-induced diabetic rats.  Cell Biochem Funct. 2003;  21 121-125
  • 2 Allegra M, Reiter RJ, Tan DX, Gentile C, Tesoriere L, Livrea MA. The chemistry of melatonin's interaction with reactive species.  J Pineal Res. 2003;  34 1-10
  • 3 Anjaneyulu M, Chopra K. Effect or irbesartan on the antioxidant defence system and nitric oxide release in diabetic rat kidney.  Am J Nephrol. 2004;  24 488-496
  • 4 Brown GC. Nitric oxide and mitochondrial respiration.  Biochimica et Biophysica Acta. 1999;  1411 351-369
  • 5 Cadenas E, Poderoso JJ, Antunes F, Boveris A. Analysis of the pathways of nitric oxide utilization in mitochondria.  Free Radic Res. 2000;  33 747-756
  • 6 Cam M, Yavuz O, Guven A, Ercan F, Buken N, Ustundag N. Protective effects of chronic melatonin treatment against renal injury in streptozotocin-induced diabetic rats.  J Pineal Res. 2003;  35 212-220
  • 7 Chatterjee PK, Patel NS, Sivarajah A, Kvale EO, Dugo L, Cuzzocrea S, Brown PA, Stewart KN, Mota-Filipe H, Britti D, Yaqoop MM, Thiemermann C. GW27150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemi/reperfusion injury.  Kidney Int. 2003;  63 853-865
  • 8 Cortos NK, Wakid NW. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method.  Clin Chem. 1990;  36 1440-1443
  • 9 Erdogan H, Fadillioglu E, Yagmurca M, Ucar M, Irmak MK. Protein oxidation and lipid peroxidation after renal ischemia reperfusion injury: protective effects of erdosteine and N-acetylcysteine.  Urol Res. 2006;  34 41-46
  • 10 Esterbauer H, Cheeseman KH. Methods in Enzymology. In: Packer L, Glazer AN eds Determination of aldehydic lipid peroxidation products: Malonaldehyde and 4-hydroxynonenal; Oxygen radicals in biological systems. Academic Press, California 1990 pp. 407-421
  • 11 Feillet-Coudray C, Rock E, Coudray C, Grzelkowska K, Azais-Braesco V, Dardevet D, Mazur A. Lipid peroxidation and antioxidant status in experimental diabetes.  ClinChim Acta. 1999;  284 31-43
  • 12 Gauhier TW, Davenpeck KL, Lefer AM. Nitric oxide attenuates leucocyte-endothelial interaction via P-selectin in splanchnic ischemia-reperfusion.  Am J Physiol. 1994;  267 G562-G568
  • 13 Gil-Del Valle L, De La C Millian L, Toledo A, Vilaro N, Tapanes R, Otero MA. Altered redox status in patients with diabetes mellitus type I.  Pharmacol Res. 2005;  51 375-380
  • 14 Goor Y, Peer G, Iaina A, Blum M, Wollman Y, Chernihovsky T, Silverberg D, Cabili S. Nitric oxide in ischaemic acute renal failure of streptozotocin diabetic rats.  Diabetologia. 1996;  39 1036-1040
  • 15 Ha H, Yoon SJ, Kim KH. High glucose can induce lipid peroxidaiton in the isolated rat glomeruli.  Kidney Int. 1994;  46 1620-1626
  • 16 Ha H, Lee SH, Kim KH. Effects of rebamipide in a model of experimental diabetes and on the synthesis of transforming growth factor-β and fibronectin, lipid peroxidation induced by high glucose in cultured mesangial cells.  J Pharmacol Exp Ther. 1997;  281 1462-1497
  • 17 Ha H, Kim KH. Pathogenesis of diabetic nephropathy: the role of oxidative stress and protein kinase C.  Diabetes Res Clin Pract. 1999;  45 147-151
  • 18 Hercule H, Oyekan A. Renal cytochrome p450 oxygenases and preglomerular vascular response to arachidonic acid and endothelin-1 following ischemia/reperfusion.  J Pharmacol Exp Ther. 2002;  302 717-724
  • 19 Holmberg SR, Cumming DV, Kusoma Y, Hearse DJ, Poole-Wilson PA, Shattock MJ, Williams AJ. Reactive oxygen species modify the structure and function of the cardiac sarcoplasmic reticulum calcium-release channel.  Cardioscience. 1991;  2 19-25
  • 20 Irmak MK, Koltuksuz U, Kutlu NO, Yagmurca M, Ozyurt H, Karaman A, Akyol O. The effect of caffeic acid phehethyl ester on ischemia-reperfusion injury in comparison with alpha-tocopherol in rat kidneys.  Urol Res. 2001;  29 190-193
  • 21 Jaworek J, Leja-Szpak A, Bonior J, Nawrot K, Tomaszewska R, Stachura J, Sendur R, Pawlik W, Brzozowski T, Konturek ST. Protective effect of melatonin and its precursor L-tryptophan on acute pancreatitis induced by caerulein overstimulation or ischemia/reperfusion.  J Pineal Res. 2003;  34 40-52
  • 22 Kang DH, Kim YG, Andoh TF, Gordon KL, Suga S, Mazzali M, Jefferson JA, Hughes J, Bennett W, Schreiner GF, Johnson RJ. Post-cyclosporine-mediated hypertension and nephropathy: amelioration by vascular endothelial growth factor.  Am J Physiol Renal Physiol. 2001;  280 F727-F736
  • 23 Kilic E, Ozdemir YG, Bolay H, Kelestimur H, Dalkara T. Pinealectomy aggravates and melatonin administration attenuates brain damage in focal ischemia.  J Cereb Blood Flow Metab. 1999;  19 511-516
  • 24 Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leucocyte adhesion.  Proc Natl Acad Sci USA. 1991;  88 4651-4655
  • 25 Kuramochi G, Homma S. Postischemic recovery process of renal oxygen consumption in normal and streptozotocin diabetic rats.  Ren Fail. 1993;  15 587-594
  • 26 Lagneux C, Joyeux M, Demenge P, Ribuot C, Godin-Ribuot D. Protective effects of melatonin against ischemia-reperfusion injury in the isolated rat heart.  J Life Sci. 2000;  66 503-509
  • 27 Lee HB, Yu MR, Yang Y, Jiang Z, Ha H. Reactive oxygen species-regulated signaling pathways in diabetic nephropathy.  J Am Soc Nephrol. 2003;  14 S241-S245
  • 28 Levine RL, Garland D, Oliver CN, Amica A, Climent I, Lenz AG, Ahn BW, Shalties S, Stantman ER. Methods in Enzymology. In: Packer L, Glazer AN eds Determination of carbonyl content in oxidatively modified proteins: Oxygen radicals in biological systems. California, Academic Pres 1990 pp. 464-478
  • 29 Lizasoaine L, Moro MA, Knowles RG, Darley-Usmar V, Moncado S. Nitric oxide and peroxynitrite exert distinct effects on mitochondrial respiration which are differentially blocked by glutathione or glucose.  Biochem J. 1996;  314 877-880
  • 30 Lowry O, Rosenbraugh N, Farr L, Rondall R. Protein measurement with folin-phenol reagent.  J Biol Chem. 1951;  183 265-275
  • 31 Locatelli F, Pozzoni P, Del Vecchio L. Renal replacement therapy in patients with diabetes and end-stage renal disease.  J Am Soc Nephrol. 2004;  15 S25-S29
  • 32 Maharaj DS, Anoopkumar-Dukie S, Giass BD, Antunes EM, Lack B, Walker RB, Daya S. The identification of the UV degradants of melatonin and their ability to scavenge radicals.  J Pineal Res. 2002;  32 257-261
  • 33 Melin J, Hellberg O, Akyurek M, Kallskeg O, Larsson E, Fellstrom BC. Ischemia causes rapidly progssive nephropathy in the diabetic rat.  Kidney Int. 1997;  52 985-991
  • 34 Melin J, Hellberg O, Fellström B. Hyperglisemia and renal ischemia-reperfusion injury.  Nephrol Dial Transplant. 2003;  18 460-462
  • 35 Paller MS, Hoidal J, Ferris TF. Oxygen free radicals in ischemic acute renal failure in the rat.  J Clin Invest. 1984;  74 1156-1164
  • 36 Paller MS. Acute renal failure:controversies, clinical trials, and future directions.  Semin Nephrol. 1998;  18 482-489
  • 37 Reiter RJ, Tan DX, Osuma C, Gitto E. Actions of melatoninin the reduction of oxidative stress: a review.  J Biomed Res. 2000;  7 444-458
  • 38 Reiter RJ, Tan DX, Mayo JC, Sainz RM, Leon J, Czarnocki Z. Pharmacological actions of melatonin in oxygen radical pathophysiology.  Acta Biochim Pol. 2003;  50 1129-1146
  • 39 Rhoden EL, Rhoden CR, Lucas ML, Pereira-Lima L, Zettler C, Bello-Klein A. The role of nitric oxide pathway in the renal ischemia-reperfusion injury rats.  Transplant Immunol. 2002;  10 277-284
  • 40 Rodriguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ. Regulation of antioxidant enzymes: a significant role for melatonin.  J Pineal Res. 2004;  36 1-9
  • 41 Rodriguez-Reynoso S, Leal C, Portilla-De-Buen E, Olivares N. Effects of exogenous melatonin on hepatic energetic status during ischemia-reperfusion: possible role of TNF-α and nitirc oxide.  J Surg Res. 2001;  110 141-149
  • 42 Rodriguez-Reynoso S, Leal C, Portilla-De-Buen E, Castillo JC, Ramos-Solano F. Melatonin ameliorates renal ischemia/reperfusion injury.  J Surg Res. 2004;  116 242-247
  • 43 Rouslin W. Mitochondrial complexes I, II, III, IV, and V in myocardial ischemia and autolysis.  Am J Physiol Heart Circ Physiol. 1983;  244 H743-H748
  • 44 Ruiz-Munoz LM, Vidal VF, Lamreabe I. Enaraplilat inhibits hydrogen peroxide production by murine mesangial cells exposed to high glucose concentrations.  Nephrol Dial Transplant. 1997;  12 456-464
  • 45 Sack RL, Lewy AJ, Erb DL, Vollmer WM, Singer CM. Human melatonin production decreases with age.  J Pineal Res. 1986;  3 379-388
  • 46 Sack RL, Lewy AJ, Hughes RJ. Use of melatonin for sleep and circadian rhythm disorders.  Ann Med. 1998;  30 115-121
  • 47 Sahna E, Acet A, Ozer MK, Olmez E. Myocardial ischemia-reperfusion in rats: reduction of infarct size by either supplemental physiological or pharmacological doses of melatonin.  J Pineal Res. 2002;  33 234-238
  • 48 Sahna E, Parlakpinar H, Ozturk F, Cigremi° Y, Acet A. The protective effects of on renal ischemia-reperfusion injury in rats.  Urol Res. 2003;  31 188-193
  • 49 Sener G, Sehirli AO, Keyer-Uysal M, Arbak S, Ersoy Y, Yegen BC. The protective effect of melatonin on renal ischemia-reperfusion injury in the rat.  J Pineal Res. 2002;  32 120-126
  • 50 Schwartz F, Schwartz D, Traskonov M, Chernichovsky T, Wollman Y, Gnessin E, Topisky I, Levo Y, Iaina A. L-Arginine transport is augmented through up-regulation of tubular CAT-2 mRNA in ischemic acute renal failure in rats.  Kidney Int. 2002;  62 1700-1706
  • 51 Tan DX, Manchester LC, Burkhardt S, Sainz RM, Mayo JC, Kohen R, Shohami E, Huo YS, Hardeland R, Reiter RJ. N1-acetyl-N2-formyl-5-methoxykynuramine, a biogenic amine and melatonin metabolite, functions as a potent antioxidant.  FASEB J. 2001;  15 2294-2296
  • 52 Tan DX, Reiter RJ, Manchester LC, Yan MT, El-Sawi M, Sainz RM, Mayo JC, Kohen R, Allegra M, Hardeland R. Chemical and physical properties and potential mechanisms: melatonin as a broad-spectrum antioxidant and free radical scavenger.  Curr Top Med Chem. 2002;  2 181-198
  • 53 Valdivielso JM, Crespo C, Alonso JR, Martinez-Salgado C, Eleno N, Arevolo M, Perez-Barriocanol F, Lopez-Novoa JM. Renal ischemiain the rat stimulates glomerular nitric oxide synthesis.  Am J Physiol Regul Integr Comp Physiol. 2001;  28 R771-R779
  • 54 Vanecek J. Celluler mechanisms of melatonin action.  Physiol Rev. 1998;  78 687-721
  • 55 Venkateswaran S, Pari L, Suguna L, Chandrakasan G. Modulatory effect of Coccinia indica on aortic collagen in streptozotocin-induced diabetic rats.  Clin Exp Pharmacol Physiol. 2003;  30 157-163
  • 56 Wald H, Markowitz H, Zevin S, Popovtzer MM. Opposite effects of diabetes on nephrotoxic and ischemic acute tubular necrosis.  Proc Soc Exp Biol Med. 1990;  195 51-56
  • 57 Walker LM, Walker PD, Imam SZ, Ali SF, Mayeux PR. Evidence for peroxynitrite in renal ischemia-reperfusion injury: studies with the inducible nitric oxide synthase inhibitor L-N(6)-(1-Iminoethyl) lysine.  J Pharmacol Exp Ther. 2000;  295 417-422
  • 58 Weight SC, Bell PRF, Nicholson ML. Renal ischemia-reperfusion injury.  Br J Surg. 1996;  83 162-170
  • 59 Zeitzer JM, Daniels JE, Duffy JF. Do Plasma melatonin concentrations decline with age?.  Am J Med. 1999;  107 432-436

Correspondence

Z. Kurcer

Department of Pharmacology

Faculty of Medicine

Harran University

63200 Sanliurfa

Turkey

Phone: +90/414/312/84 56 (2491)

Fax: +90/414/313/96 15

Email: zykurcer@yahoo.com

Email: zykurcer@harran.edu.tr

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