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Int J Sports Med 2010; 31(12): 847-853
DOI: 10.1055/s-0030-1265205
Physiology & Biochemistry

© Georg Thieme Verlag KG Stuttgart · New York

Protective Effect of Erythropoietin on Renal Injury Induced by Acute Exhaustive Exercise in the Rat

X. Lin1 , S. Qu1 , M. Hu2 , C. Jiang1 , 3
  • 1Medical College of Hunan Normal University, Changsha, China
  • 2Public Health College of Central South University, Changsha, China
  • 3University of Linköping, Department of Clinical and Experimental Medicine, Sweden
Further Information

Publication History

accepted after revision August 23, 2010

Publication Date:
11 November 2010 (online)

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Abstract

We investigated the protective effect of Erythropoietin (EPO) analogue rHuEPO on renal injury induced by acute exhaustive exercise in the rat. Rats were randomly allocated to one of 3 groups: normal control (C), exhaustive exercise test (ET) and EPO pre-treatment (rHuEPO 2 000 U/kg) plus ET (EPO+ET). Compared with controls, animals in the ET group had increased serum urea nitrogen, serum creatinine, urine protein, and renal tissue malondialdehyde (MDA) and decreased renal tissue nitric oxide (NO), nitric oxide synthase (NOS) and superoxide dismutase (SOD) activities. There was severe damage in renal tubular epithelial cells with a lot of cell apoptosis, and TUNEL assay revealed a remarkably high apoptotic index (p<0.01). Changes in renal function and kidney tissue were much less in the EPO+ET group (p<0.05) and the apoptotic index was much lower than in the ET group (18.45±0.32 vs. 27.55±0.49, p<0.05). EPO pretreatment thus significantly prevented renal cell apoptosis, and counteracted high MDA and low NO and NOS renal contents induced by exhaustive exercise. The data point to a potential value of EPO in preventing the acute renal injury after exhaustive exercise.

Key words

erythropoietin - exhaustive exercise - apoptosis - kidney - rat

References

  • 1 Aslani A, Babaee Bigi MA, Moaref AR, Aslani A. Effect of extreme exercise on myocardial function as assessed by tissue Doppler imaging.  Echocardiography. 2009;  26 1036-1040
    CrossrefPubMedGoogle Scholar
  • 2 Bonegio R, Lieberthal W. Role of apoptosis in the pathogenesis of acute renal failure.  Curr Opin Nephrol Hypertens. 2002;  11 301-308
    CrossrefPubMedGoogle Scholar
  • 3 Burger D, Xenocostas A, Feng QP. Molecular basis of cardioprotection by erythropoietin.  Curr Mol Pharmacol. 2009;  2 56-69
    CrossrefPubMedGoogle Scholar
  • 4 Chatterjee PK. Pleiotropic renal actions of erythropoietin.  Lancet. 2005;  365 1890-1892
    CrossrefPubMedGoogle Scholar
  • 5 Chirpaz-Oddou MF, Favre-Juvin A, Flore P, Eterradossi J, Delaire M, Grimbert F, Therminarias A. Nitric oxide response in exhaled air during an incremental exhaustive exercise.  J Appl Physiol. 1997;  82 1311-1318
    PubMedGoogle Scholar
  • 6 Chung H, Lee H, Lamoke F, Hrushesky WJ, Wood PA, Jahng WJ. Neuroprotective role of erythropoietin by antiapoptosis in the retina.  J Neurosci Res. 2009;  87 2365-2374
    CrossrefPubMedGoogle Scholar
  • 7 Fishbane S, Ragolia L, Palaia T, Johnson B, Elzein H, Maesaka JK. Cytoprotection by darbepoetin/epoetin alfa in pig tubular and mouse mesangial cells.  Kidney Int. 2004;  65 452-458
    CrossrefPubMedGoogle Scholar
  • 8 Grasso G, Graziano F, Sfacteria A, Carletti F, Meli F, Maugeri R, Passalacqua M, Certo F, Fazio M, Buemi M, Iacopino DG. Neuroprotective effect of erythropoietin and darbepoetin alfa after experimental intracerebral hemorrhage.  Neurosurgery. 2009;  65 763-769
    CrossrefPubMedGoogle Scholar
  • 9 Hackney AC, Fahrner CL, Gulledge TP. Basal reproductive hormonal profiles are altered in endurance trained men.  J Sports Med Phys Fitness. 1998;  38 138-141
    PubMedGoogle Scholar
  • 10 Harriss DJ, Atkinson G. International Journal of Sports Medicine – Ethical Standards in Sport and Exercise Science Research.  Int J Sports Med. 2009;  30 701-702
    Google Scholar
  • 11 Hu W, Li X. Changes of NO and NOS activities in hippocampus of the rats after exhaustive swimming.  Chin J Sports Medicine. 2005;  24 719-720
    PubMedGoogle Scholar
  • 12 Jaquet K, Krause K, Tawakol-Khodai M, Geidel S, Kuck KH. Erythropoietin and VEGF exhibit equal angiogenic potential.  Microvasc Res. 2002;  64 326-333
    CrossrefPubMedGoogle Scholar
  • 13 Johnson DW, Pat B, Vesey DA, Guan Z, Endre Z, Gobe GC. Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure.  Kidney Int. 2006;  69 1806-1813
    CrossrefPubMedGoogle Scholar
  • 14 Juul S. Erythropoietin in the central nervous system, and its use to prevent hypoxic-ischemic brain damage.  Acta Paediatr Suppl. 2002;  91 36-42
    CrossrefPubMedGoogle Scholar
  • 15 Kaushal GP, Basnakian AG, Shah SV. Apoptotic pathways in ischemic acute renal failure.  Kidney Int. 2004;  66 500-506
    CrossrefPubMedGoogle Scholar
  • 16 Komarievtseva IO, Orlova OA, Blahodarenko I. Vmist oksydu azotu v nyrkakh za aktyvatsii apoptozu.  Ukr Biokhim Zh. 2002;  74 116-119
    PubMedGoogle Scholar
  • 17 Kone BC. Nitric oxide in renal health and disease.  Am J Kidney Dis. 1997;  30 311-333
    CrossrefPubMedGoogle Scholar
  • 18 Kone BC, Baylis C. Biosynthesis and homeostatic roles of nitric oxide in the normal kidney.  Am J Physiol. 1997;  272 F561-F578
    PubMedGoogle Scholar
  • 19 Kruger K, Frost S, Most E, Volker K, Pallauf J, Mooren FC. Exercise affects tissue lymphocyte apoptosis via redox-sensitive and Fas-dependent signaling pathways.  Am J Physiol. 2009;  296 R1518-R1527
    PubMedGoogle Scholar
  • 20 Lekhi C, Gupta PH, Singh B. Influence of exercise on oxidant stress products in elite Indian cyclists.  Br J Sports Med. 2007;  41 691-693
    CrossrefPubMedGoogle Scholar
  • 21 Li S, Qu S, Tang C. Research on effects of acute exercise to exhaust on liver apoptosis in rats.  J Beijing Sports University. 2006;  29 634-636
    PubMedGoogle Scholar
  • 22 Mahakkanukrauh A, Sangchan A, Mootsikapun P. Exertional rhabdomyolysis following excessive exercise of university freshman cheer-training.  J Med Assoc Thai. 2003;  86 789-792
    PubMedGoogle Scholar
  • 23 Manukhina EB, Lapshin AV, Meerson FZ, Mikoian VD, Kubrina LN, Vanin AF. Vliianie adaptatsii k fizicheskoi nagruzke na endoteliioposredovannye reaktsii izolirovannykh sosudov i produktsiiu NO u krys.  Fiziol Zh Im I M Sechenova. 1996;  82 54-60
    PubMedGoogle Scholar
  • 24 Mihov D, Bogdanov N, Grenacher B, Gassmann M, Zund G, Bogdanova A, Tavakoli R. Erythropoietin protects from reperfusion-induced myocardial injury by enhancing coronary endothelial nitric oxide production.  Eur J Cardiothorac Surg. 2009;  35 839-846
    CrossrefPubMedGoogle Scholar
  • 25 Patel NS, Sharples EJ, Cuzzocrea S, Chatterjee PK, Britti D, Yaqoob MM, Thiemermann C. Pretreatment with EPO reduces the injury and dysfunction caused by ischemia/reperfusion in the mouse kidney in vivo.  Kidney Int. 2004;  66 983-989
    CrossrefPubMedGoogle Scholar
  • 26 Sakanaka M, Wen TC, Matsuda S, Masuda S, Morishita E, Nagao M, Sasaki R. In vivo evidence that erythropoietin protects neurons from ischemic damage.  Proc Natl Acad Sci U S A. 1998;  95 4635-4640
    CrossrefPubMedGoogle Scholar
  • 27 Sharples EJ, Patel N, Brown P, Stewart K, Mota-Philipe H, Sheaff M, Kieswich J, Allen D, Harwood S, Raftery M, Thiemermann C, Yaqoob MM. Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion.  J Am Soc Nephrol. 2004;  15 2115-2124
    CrossrefPubMedGoogle Scholar
  • 28 Singbartl K, Green SA, Ley K. Blocking P-selectin protects from ischemia/reperfusion-induced acute renal failure.  FASEB J. 2000;  14 48-54
    PubMedGoogle Scholar
  • 29 Urhausen A, Kindermann W. Diagnosis of overtraining: what tools do we have?.  Sports Med. 2002;  32 95-102
    CrossrefPubMedGoogle Scholar
  • 30 Vesey DA, Cheung C, Pat B, Endre Z, Gobe G, Johnson DW. Erythropoietin protects against ischaemic acute renal injury.  Nephrol Dial Transplant. 2004;  19 348-355
    CrossrefPubMedGoogle Scholar
  • 31 Wappler F, Fiege M, Steinfath M, Agarwal K, Scholz J, Singh S, Matschke J, Schulte Am Esch J. Evidence for susceptibility to malignant hyperthermia in patients with exercise-induced rhabdomyolysis.  Anesthesiology. 2001;  94 95-100
    CrossrefPubMedGoogle Scholar
  • 32 Westenfelder C, Biddle DL, Baranowski RL. Human, rat, and mouse kidney cells express functional erythropoietin receptors.  Kidney Int. 1999;  55 808-820
    CrossrefPubMedGoogle Scholar
  • 33 Wijsman JH, Jonker RR, Keijzer R, van de Velde CJ, Cornelisse CJ, van Dierendonck JH. A new method to detect apoptosis in paraffin sections: in situ end-labeling of fragmented DNA.  J Histochem Cytochem. 1993;  41 7-12
    CrossrefPubMedGoogle Scholar
  • 34 Yang CW, Li C, Jung JY, Shin SJ, Choi BS, Lim SW, Sun BK, Kim YS, Kim J, Chang YS, Bang BK. Preconditioning with erythropoietin protects against subsequent ischemia-reperfusion injury in rat kidney.  FASEB J. 2003;  17 1754-1755
    PubMedGoogle Scholar
  • 35 Zhang G, Zhang W. Effects of supplement of lysine on Bax and Bcl-2 gene expression in liver and heart of the rat induced by acute exhaustive exercise.  Chin Sports Sci. 2008;  28 48-52
    PubMedGoogle Scholar

Correspondence

Prof. Shulin Qu

Medical College of Hunan

Normal University

Department of Physiology

Tongzipo Road 371

410013 Changsha

China

Phone: 008673188630333

Fax: 008673188630333

Email: qushulin07@yahoo.com.cn