Short-term antioxidant diet prevents hyperfiltration in young male rat kidney subjected to ischemia/reperfusion injury


Objectives: The process of transplantation is associated with exposure to both long and short cold and warm ischemic times that result in ischemia/reperfusion injury. Oxidative stress contributes to tissue fibrosis, renal dysfunction, and/or rejection. Treatments that scavenge oxygen free radicals and have antioxidant properties can ameliorate the damaging results in renal grafts following ischemia/reperfusion injury. The present study tests the hypothesis that an antioxidant-fortified diet given to rats before and after renal ischemia/reperfusion injury will reduce the kidney damage that results and improve renal function. Endothelial and inducible nitric oxide synthases may change with tissue injury, including ischemia/ reperfusion. Materials and Methods: Male Wistar rats were subjected to ischemia/reperfusion injury at 7 or 19 weeks of age with or without dietary antioxidant supplementation. One week later, glomerular filtration rate, mean arterial pressure and urinary nitric oxide were measured, and renal endothelial and inducible nitric oxide synthases examined. Results: The glomerular filtration rate was elevated more than two-fold above the normal range  at 8 weeks in animals on the regular diet exposed to ischemia/reperfu- sion, while in the 8 week antioxidant-fortified diet group the glomerular filtration rate was normal. Also, in 8 week rats, levels of endothelial nitric oxide synthase protein in cortex were higher on the regular than on the antioxidant-fortified diet. Conclusion: Early after ischemia/reperfusion injury renal endothelial nitric oxide synthase levels rise, possibly contributing to vascular dilation and hyperperfusion, and an antioxidant-fortified diet can ameliorate these changes in the younger age group.

Share and Cite:

Slyvka, Y. , Nowak, F. , Hayes, T. and Inman, S. (2013) Short-term antioxidant diet prevents hyperfiltration in young male rat kidney subjected to ischemia/reperfusion injury. Open Journal of Molecular and Integrative Physiology, 3, 36-41. doi: 10.4236/ojmip.2013.31006.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Thiruchelvam, P.T., Willicombe, M., Hakim, N., Taube, D. and Papalois, V. (2011) Renal transplantation. BMJ, 343, d7300. doi:10.1136/bmj.d7300
[2] Kaisar, M.O., Nicol, D.L., Hawley, C.M., Mudge, D.W., Johnson, D.W., Preston, J.M., Wall, D.R., Griffin, A.D., Campbell, S.B. and Isbel, N.M. (2008) Change in live donor characteristics over the last 25 years: A single centre experience. Nephrology (Carlton), 13, 646-650. doi:10.1111/j.1440-1797.2008.01039.x
[3] Sahin, S., Manga Sahin, G., Turkmen, A. and Sever, M.S. (2006) Utilization of elderly donors in living related kidney transplantation. Transplantation Proceedings, 38, 385-387. doi:10.1016/j.transproceed.2005.12.090
[4] Stallone, G., Infante, B. and Gesualdo, L. (2010) Older donors and older recipients in kidney transplantation. Journal of Nephrology, 23, S98-S103.
[5] Gandhi, C., Zalawadia, R. and Balaraman, R. (2008) Nebivolol reduces experimentally induced warm renal ischemia reperfusion injury in rats. Renal Failure, 30, 921-930. doi:10.1080/08860220802353900
[6] Feng, L., Ke, N., Cheng, F., Guo, Y., Li, S., Li, Q. and Li, Y. (2011) The protective mechanism of ligustrazine against renal ischemia/reperfusion injury. Journal of Surgical Research, 166, 298-305. doi:10.1016/j.jss.2009.04.005
[7] Kosieradzki, M. and Rowinski, W. (2008) Ischemia/ reperfusion injury in kidney transplantation: Mechanisms and prevention. Transplantation Proceedings, 40, 3279-3288. doi:10.1016/j.transproceed.2008.10.004
[8] De Fijter, J.W. (2005) The impact of age on rejection in kidney transplantation. Drugs Aging, 22, 433-449. doi:10.2165/00002512-200522050-00007
[9] Nafar, M., Sahraei, Z., Salamzadeh, J., Samavat, S. and Vaziri, N.D. (2011) Oxidative stress in kidney transplanttation: Causes, consequences, and potential treatment. Iranian Journal of Kidney Diseases, 5, 357-372.
[10] Kim, J., Jang, H.S. and Park, K.M. (2010) Reactive oxygen species generated by renal ischemia and reperfusion trigger protection against subsequent renal ischemia and reperfusion injury in mice. American Journal of Physiology—Renal Physiology, 298, F158-F166. doi:10.1152/ajprenal.00474.2009
[11] Kim, J., Seok, Y.M. Jung, K.J. and Park, K.M. (2009) Reactive oxygen species/oxidative stress contributes to progression of kidney fibrosis following transient ischemic injury in mice. American Journal of Physiology— Renal Physiology, 297, F461-F470. doi:10.1152/ajprenal.90735.2008
[12] Karaman, A., Turkmen, E., Gursul, C., Tas, E. and Fadillioglu, E. (2006) Prevention of renal ischemia/reperfusion-induced injury in rats by leflunomide. International Journal of Urology, 13, 1434-1441. doi:10.1111/j.1442-2042.2006.01592.x
[13] Bhalodia, Y., Sheth, N., Vaghasiya, J. and Jivani, N. (2010) Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury. Renal Failure, 32, 1088-1094. doi:10.3109/0886022X.2010.504911
[14] Ozer Sehirli, A., Sener, G. and Ercan, F. (2009) Protective effects of pycnogenol against ischemia reperfusioninduced oxidative renal injury in rats. Renal Failure, 31, 690-697. doi:10.3109/08860220903085971
[15] Korkmaz, A. and Kolankaya, D. (2010) Protective effect of rutin on the ischemia/reperfusion induced damage in rat kidney. Journal of Surgical Research, 164, 309-315. doi:10.1016/j.jss.2009.03.022
[16] Chugh, G., Lokhandwala, M.F. and Asghar, M. (2011) Oxidative stress alters renal D1 and AT1 receptor functions and increases blood pressure in old rats. American Journal of Physiology—Renal Physiology, 300, F133F138. doi:10.1152/ajprenal.00465.2010
[17] Yang, H. and Fogo, A.B. (2010) Cell senescence in the aging kidney. Journal of the American Society of Nephrology, 21, 1436-1439. doi:10.1681/ASN.2010020205
[18] Mount, P.F. and Power, D.A. (2006) Nitric oxide in the kidney: Functions and regulation of synthesis. Acta Physiologica, 187, 433-446. doi:10.1111/j.1748-1716.2006.01582.x
[19] Chatterjee, P.K. (2007) Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: A comprehensive review. Naunyn-Schmiedeberg’s Archives of Pharmacology, 376, 1-43. doi:10.1007/s00210-007-0183-5
[20] Lien, Y.H., Lai, L.W. and Silva, A.L. (2003) Pathogenesis of renal ischemia/reperfusion injury: Lessons from knockout mice. Life Sciences, 74, 543-552. doi:10.1016/j.lfs.2003.08.001
[21] Zhou, X.J., Vaziri, N.D., Zhang, J., Wang, H.W. and Wang, X.Q. (2002) Association of renal injury with nitric oxide deficiency in aged SHR: prevention by hypertension control with AT1 blockade. Kidney International, 62, 914-921. doi:10.1046/j.1523-1755.2002.00516.x
[22] Goettsch, W., Lattmann, T., Amann, K., Szibor, M., Morawietz, H., Munter, K., Muller, S.P., Shaw, S. and Barton, M. (2001) Increased expression of endothelin-1 and inducible nitric oxide synthase isoform II in aging arteries in vivo: Implications for atherosclerosis. Biochemical and Biophysical Research Communications, 280, 908-913. doi:10.1006/bbrc.2000.4180
[23] Huisman, A., Vos, I., van Faassen, E.E., Joles, J.A., Grone, H.J., Martasek, P., van Zonneveld, A.J., Vanin, A.F. and Rabelink, T.J. (2002) Anti-inflammatory effects of tetrahydrobiopterin on early rejection in renal allografts: Modulation of inducible nitric oxide synthase. FASEB Journal, 16, 1135-1137.
[24] MacMillan-Crow, L.A., Crow, J.P., Kerby, J.D., Beckman, J.S. and Thompson, J.A. (1996) Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts. Proceedings of the National Academy of Sciences of the USA, 93, 1185311858. doi:10.1073/pnas.93.21.11853
[25] Shoskes, D.A., Xie, Y. and Gonzalez-Cadavid, N.F. (1997) Nitric oxide synthase activity in renal ischemiareperfusion injury in the rat: Implications for renal transplantation. Transplantation, 63, 495-500. doi:10.1097/00007890-199702270-00002
[26] Slyvka, Y., Inman, S.R., Malgor, R., Jackson, E.J., Yee, J., Oshogwemoh, O., Adame, J. and Nowak, F.V. (2009) Protective effects of antioxidant-fortified diet on renal function and metabolic profile in obese Zucker rat. Endocrine, 35, 89-100. doi:10.1007/s12020-008-9121-7
[27] Slyvka, Y., Wang, Z., Yee, J., Inman, S.R. and Nowak, F.V. (2011) Antioxidant diet, gender and age affect renal expression of nitric oxide synthases in obese diabetic rats. Nitric Oxide, 24, 50-60. doi:10.1016/j.niox.2010.11.004
[28] Brigelius-Flohe, R. (2007) Adverse effects of vitamin E by induction of drug metabolism. Genes & Nutrition, 2, 249-256. doi:10.1007/s12263-007-0055-0
[29] Douillet, C., Tabib, A., Bost, M., Accominotti, M., Borson-Chazot, F. and Ciavatti, M. (1996) A selenium supplement associated or not with vitamin E delays early renal lesions in experimental diabetes in rats. Proceedings of the Society for Experimental Biology and Medicine, 211, 323-331.
[30] Hamilton, S.J., Chew, G.T. and Watts, G.F. (2007) Therapeutic regulation of endothelial dysfunction in type 2 diabetes mellitus. Diabetes and Vascular Disease Research, 4, 89-102. doi:10.3132/dvdr.2007.026
[31] Montonen, J., Knekt, P., Jarvinen, R. and Reunanen, A. (2004) Dietary antioxidant intake and risk of type 2 diabetes. Diabetes Care, 27, 362-366. doi:10.2337/diacare.27.7.1845-a
[32] Inman, S.R., Plott, W.K., Pomilee, R.A., Antonelli, J.A. and Lewis, R.M. (2003) Endothelin-receptor blockade mitigates the adverse effect of preretrieval warm ischemia on posttransplantation renal function in rats. Transplantation, 75, 1655-1659. doi:10.1097/01.TP.0000063127.02261.E4
[33] Inman, S.R., Davis, N.A., Mazzone, M.E., Olson, K.M., Lukaszek, V.A. and Yoder, K.N. (2005) Simvastatin and L-arginine preserve renal function after ischemia/reperfusion injury. American Journal of the Medical Sciences, 329, 13-17. doi:10.1097/00000441-200501000-00003
[34] Mount, P.F., Kemp, B.E. and Power, D.A. (2007) Regulation of endothelial and myocardial NO synthesis by multi-site eNOS phosphorylation. Journal of Molecular and Cellular Cardiology, 42, 271-279. doi:10.1016/j.yjmcc.2006.05.023
[35] Kusaka, J., Koga, H., Hagiwara, S., Hasegawa, A., Kudo, K. and Noguchi, T. (2012) Age-dependent responses to renal ischemia-reperfusion injury. Journal of Surgical Research, 172, 153-158. doi:10.1016/j.jss.2010.08.034
[36] Vinas, J.L., Sola, A., Genesca, M., Alfaro, V., Pi, F. and Hotter, G. (2006) NO and NOS isoforms in the development of apoptosis in renal ischemia/reperfusion. Free Radical Biology & Medicine, 40, 992-1003. doi:10.1016/j.freeradbiomed.2005.10.046
[37] Moudgil, A. and Bagga, A. (1999) Evaluation and treatment of chronic renal failure. Indian Journal of Pediatrics, 66, 241-253. doi:10.1007/BF02761215
[38] Veelken, R., Hilgers, K.F., Hartner, A., Haas, A., Bohmer, K.P. and Sterzel, R.B. (2000) Nitric oxide synthase isoforms and glomerular hyperfiltration in early diabetic nephropathy. Journal of the American Society of Nephrology, 11, 71-79.
[39] Park, K.M., Kim, J.I., Ahn, Y., Bonventre, A.J. and Bonventre, J.V. (2004) Testosterone is responsible for enhanced susceptibility of males to ischemic renal injury. The Journal of Biological Chemistry, 279, 52282-52292. doi:10.1074/jbc.M407629200

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.