Effect of moderate exercise on renal changes and oxidative stress in ovariectomized rats with type 1 diabetes mellitus

Mayane Oliveira Rebouças da Silveira , Liliany Souza de Brito Amaral , Samira Itana de Souza , Halanna Rocha Ferraz , Jéssica Alves Dias , Edilene Cândido Rocha , Fernanda de Abreu Silva , Amélia Cristina Mendes de Magalhães and Telma de Jesus Soares

Abstract
This study evaluated the aerobic exercise effects of moderate and progressive intensity on renal function and structure, and oxidative stress in ovariectomized rats with type 1 diabetes mellitus induced by streptozotocin (STZ). Eighteen Wistar rats were divided into 3 groups: OSC - ovariectomized and sedentary control rats; OSD - ovariectomized and sedentary diabetic rats; and OTD - ovariectomized and trained diabetic rats. After induction of diabetes, the OTD group was submitted to eight weeks of exercise. Twenty-four hours after the last training session urine samples were collected. Blood samples and kidneys were collected after euthanasia for renal function analysis, histology, morphometry and oxidative stress. Our results have shown a reduction of the weight gain, increase of kidney weight and postprandial glycemia in diabetic rats. However, exercise decreased glycosuria and prevented the proteinuria in OTD group rats. Focal segmental glomerulosclerosis (FSGS), juxtamedullary glomerular tuft area, tubulointerstitial lesions (TIL), brush border loss and tubular cell debridement were reduced in OTD rats. In addition, exercise training decreased urinary and plasma concentrations of thiobarbituric acid reactive substance (TBARS). Our results demonstrate the beneficial effect of progressive aerobic exercise on proteinuria, glycosuria, and renal structure in ovariectomized diabetic rats, which may be mediated in part by reduction of oxidative stress.

Keywords
Diabetes mellitus; Ovariectomy; Kidney; Exercise training.

DOI
10.21472/bjbs.061302

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References
Agarwal, D.; Elks, C. M.; Reed, S. D.; Mariappan, N.; Majid, D. S. A.; Francis, J. Chronic exercise preserves renal structure and hemodynamics in spontaneously hypertensive rats. Antioxidants & Redox Signaling, v. 16, no. 2, p. 139-152, 2012. https://doi.org/10.1089/ars.2011.3967

Albright, A. L.; Mahan, J. D.; Ward, K. M.; Sherman, W. M.; Roehrig K. L.; Kirby, T. E. Diabetic nephropathy in an aerobically trained rat model of diabetes. Medicine & Science in Sports & Exercise, v. 27, no. 9, p. 1270-1277, 1995.

Al-Trad, B.; Ashankyty, I. M.; Alaraj, M. Progesterone ameliorates diabetic nephropathy in streptozotocin-induced diabetic Rats. Diabetology & Metabolic Syndrome, 7:97, 2015. https://doi.org/10.1186/s13098-015-0097-1

Amaral, L. S. B.; Silva, J. A.; Trindade, T. M.; Ribas, W. B. D.; Macedo, C. L.; Coimbra, T. M.; Belo, N. O.; Magalhães, A. C. M.; Soares, T. J. Renal changes in the early stages of diet-induced obesity in ovariectomized rats physiological. Physiological Research, v. 63, p. 723-732, 2014.

Amaral, L. S. B.; Silva, F. A.; Correia, V. B.; Andrade, C. E.; Dutra, B. A.; Oliveira, M. V.; Magalhães, A. C. D.; Volpini, R. A.; Seguro A. C.; Coimbra T.M.; Soares, T. D. J. Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats. Experimental Biology and Medicine, v. 241, no. 4, p. 437-445, 2016. https://doi.org/10.1177/1535370215609696

Antus, B.; Hamar, P.; Kokeny, G.; Szollosi, Z.; Mucsi, I.; Nemes, Z.; Rosivall, L. Estradiol is nephroprotective in the rat remnant kidney. Nephrology Dialysis Transplantation, v. 18, no. 1, p. 54-61, 2003. https://doi.org/10.1093/ndt/18.1.54

Bangstad, H. J.; Østerby, R.; Dahl-Jørgensen, K.; Berg, K. J.; Hartmann, A.; Nyberg, G.; Bjorn, S. F.; Hanssen, K. E. Early glomerulopathy is present in young, type 1 (Insulin-Dependent) diabetic patients with microalbuminuria. Diabetologia, v. 36, p. 523-529, 1993.

Barutta, F.; Bruno, G.; Grimaldi, S.; Gruden G. Inflammation in diabetic nephropathy: Moving toward clinical biomarkers and targets for treatment. Endocrine Rewiew, v. 48, no. 3, p. 730-742, 2014. https://doi.org/10.1007/s12020-014-0437-1

Bergeron, R.; Mentor, J. S.; Côté, I.; Ngo Sock, E. T.; Rabasa-Lhoret, R.; Lavoie, J. M. Loss of ovarian estrogens causes only mild deterioration of glucose homeostasis in female ZDF rats preventable by voluntary running exercise. Hormone Metabolism Research, v. 46, no. 11, p. 774-781, 2014. https://doi.org/10.1055/s-0034-1381980

Bortolon, J. R.; Silva Junior, A. J. A.; Murata, G. M.; Newsholme, P.; Curi R.; Pithon-Curi, T. C.; Hatanaka E. Persistence of inflammatory response to intense exercise in diabetic rats. Experimental Diabetes Research, v. 2012, Article ID 213986, 2012. https://doi.org/10.1155/2012/213986

Camargo, I. C. C.; Gênova, T. C.; Machado, M. C. P.; Frei, F.; Mesquita, S. F. P. Administração experimental de esteróide anabólico androgênico e álcool causa alterações histológicas e morfométricas nos ovários e útero de ratas adultas. Bioscience Journal, v. 27, no. 4, p. 656-665, 2011.

Chin, M.; Isono, M.; Isshiki, K.; Araki, A.; Sugimoto, T.; Guo, B.; Sato, H.; Haneda, M.; Kashiwagi, A.; Koya, D. Estrogen and raloxifene, a selective estrogen receptor modulator, ameliorate renal damage in db/db mice. American Journal of Pathology, v. 166, no. 11, p. 1629-1636, 2005. https://doi.org/10.1210/en.2004-1653

Choi, S. B.; Jang, J. S.; Park, S. Estrogen and exercise may enhance β-cell function and mass via insulin receptor substrate 2 induction in ovariectomized diabetic rats. Endocrinology, v. 146, p. 4786-4794, 2005. https://doi.org/10.1210/en.2004-1653

Ciampone, S.; Borges, R.; Lima, I. P. D.; Mesquita, F. F.; Cambiucci, E. C.; Gontijo J. A. R. Long-term exercise attenuates blood pressure responsiveness and modulates kidney angiotensin II signalling and urinary sodium excretion in SHR. Journal of Renin-Angiotensin-Aldosterone System, v. 12, p. 394-403, 2011. https://doi.org/10.1177/1470320311408750

Coelho, C. F.; Burine, R. C. Atividade física para prevenção e tratamento das doenças crônicas não transmissíveis e da incapacidade funcional. Revista de Nutrição, v. 22, no. 6, p. 937-946, 2009. https://doi.org/10.1590/S1415-52732009000600015

Coimbra, T. M.; Janssen, U.; Grone, H. J.; Ostendorf, T.; Kunter, U.; Schmidt, H.; Brabant, G.; Floege, J. Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes. Kidney International, v. 57, p. 167-182, 2000. https://doi.org/10.1046/j.1523-1755.2000.00836.x

Ebersbach-Silva, P.; Alves, T.; Fonseca, A. T.; Oliveira, M. A.; Machado, U. F.; Seraphim, P. M. Cigarette smoke exposure severely reduces peripheral insulin sensitivity without changing GLUT4 expression in oxidative muscle of Wistar rats. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 57, no. 1, p. 19-26, 2013. https://doi.org/10.1590/S0004-27302013000100003

Elliot, S. J.; Karl, M.; Berho, M.; Potier, M.; Zheng, F.; Leclercq, B.; Striker, G. E.; Strieker, L. J. Estrogen deficiency accelerates progression of glomerulosclerosis in susceptible mice. American Journal of Pathology, v .162, no. 5, p. 1441-1448, 2003. https://doi.org/10.1016/S0002-9440(10)64277-0

Fernandes, S. M.; Cordeiro, P. M.; Watanabe, M.; Fonseca, C. D.; Vattimo, M. F. F. The role of oxidative stress in streptozotocin-induced diabetic nephropathy in rats. Archives of Endocrinology and Metabolism, v, 60, p. 443-449, 2016.

Furukawa, M.; Gohda, T.; Tanimoto, M.; Tomino Y. Pathogenesis and novel treatment from the mouse model oftype 2 diabetic nephropathy. The Scientific World Journal, v. 2013, Article ID 928197, 2013. https://doi.org/10.1155/2013/928197

Guimarães, J.; Bastos, M.; Melo, M.; Carvalheiro, M. Nefropatia diabética: taxa de filtração glomerular calculada e estimada. Acta Medica Portuguesa, v. 20, no. 2, p. 145-150, 2007.

Gusmão, L.; Galvão, J.; Possante M. A resposta do rim ao esforço físico. Revista Portuguesa de Nefrologia e Hipertensão, v. 17, no. 1, p. 73-80, 2003.

Haugen, H. N. The determination of "endogenous creatinine" in plasma and urine. Scandinavian Journal of Clinical and Laboratory Investigation, v. 5, no. 1, p. 48-57, 1953. https://doi.org/10.3109/00365515309093511

Huebschmann, A. G.; Kohrt, W. M., Herlache, L.; Wolfe, P.; Daugherty, S.; Reusch, J. E. B.; Bauer, T. A.; Regensteiner, J. G. Type 2 diabetes exaggerates exercise effort and impairs exercise performance in older women. BMJ Open Diabetes Research & Care, v. 3, no. 1, e000124, 2015. https://doi.org/10.1136/bmjdrc-2015-000124

Ito, D.; Cao, P.; Kakihana, T.; Sato, E.; Suda, C.; Muroya, Y.; Ogawa, Y.; Hu, G.; Ishii, T.; Ito, O.; Kohzuki, M.; Kiyomoto, H. Chronic running exercise alleviates early progression of nephropathy with upregulation of nitric oxide synthases and suppression of glycation in Zucker diabetic rats. PLoS ONE, v. 10, no. 9, e0138037, 2015. https://doi.org/10.1371/journal.pone.0138037

Keck, M.; Romero-Aleshire, M. J.; Cai, Q.; Hoyer, P. B.; Brooks, H. L. Hormonal status affects the progression of STZ-induced diabetes and diabetic renal damage in the VCD mouse model of menopause. American Journal of Physiology-Renal Physiology, v. 293, no. 1, p. 193-199, 2007. https://doi.org/10.1152/ajprenal.00022.2007

Lagranha, C. J.; Fiorino, P.; Casarini, D. E.; Schaan, B. D.; Irigoyen, M. C. Bases moleculares da glomerulopatia diabética. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 51, p. 901-912, 2007. https://doi.org/10.1590/S0004-27302007000600003

Machado, U. F. Transportadores de glicose. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 42, p. 413-421, 1998. https://doi.org/10.1590/S0004-27301998000600003

Mankhey, R. W.; Bhatti, F.; Maric, C. 17β-estradiol replacement improves renal function and pathology associated with diabetic nephropathy. American Journal of Physiology-Renal Physiology, v. 288, no. 2, p. F399-F405, 2005. https://doi.org/10.1152/ajprenal.00195.2004

Mansouri, E.; Panahi, M.; Ghaffari, M. A.; Ghorbani, A. Effects of grape seed proanthocyanidin extract on oxidative stress induced by diabetes in rat kidney. Iranian Biomedical Journal, v. 15, no. 3, p. 100-106, 2011.

Maric, C.; Sullivan, M. D. S. Estrogens and the diabetic kidney. Gender Medicine, v. 5, Suppl. 1, p. S103-S113, 2008. https://doi.org/10.1016/j.genm.2008.03.010

Miyagi, M. Y. S.; Seelaender, M.; Castoldi, A.; Almeida, D. C.; Bacurau, A. V. N.; Andrade-Oliveira, V.; Enjiu, L. M.; Pisciottano, M.; Hayashida, C. Y.; Hiyane, M. I.; Brum, P. C.; Camara, N. O. S.; Amano, M. T. Long-term aerobic exercise protects against cisplatin-induced nephrotoxicity by modulating the expression of IL-6 and HO-1. PLoS ONE, v. 9, no. 10, e108543, 2014. https://doi.org/10.1371/journal.pone.0108543

Murussi, M.; Murussi, N.; Campagnolo, N.; Silveiro, S. P. Detecção precoce da nefropatia diabética. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 52, no. 3, p. 442-451, 2008. https://doi.org/10.1590/S0004-27302008000300004

Najas, C. S.; Pissulin, F. D. M.; Pacagnelli, F. L.; Betônico, G. N.; Almeida, I. C.; Neder, J. A. Segurança e eficácia do treinamento físico na insuficiência renal crônica. Revista Brasileira de Medicina do Esporte, v. 15, no. 5, p. 384-388, 2009. https://doi.org/10.1590/S1517-86922009000600013

Neugarten, J.; Acharya, A.; Silbiger, S. R. Effect of gender on the progression of nondiabetic renal disease a meta-analysis. Journal of the American Society of Nephrology, v. 11, no. 2, p. 319-329, 2000.

Ohkawa, H.; Ohishi, N.; Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, v. 95, no. 2, p. 351-358, 1979. https://doi.org/10.1016/0003-2697(79)90738-3

Palm, F.; Cederberg, J.; Hansell, P.; Liss, P.; Carlsson, P. O. Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension. Diabetologia, v. 46, no. 8, p. 1153-1160, 2003. https://doi.org/10.1007/s00125-003-1155-z<

Pauli, J. R.; Cintra, D. E.; Souza C. T.; Ropelle, E. R. Novos mecanismos pelos quais o exercício físico melhora a resistência à insulina no músculo esquelético. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 53, no. 4, p. 399-408, 2009. https://doi.org/10.1590/S0004-27302009000400003

Pedersen, B. K. The anti-inflammatory effect of exercise: Its role in diabetes and cardiovascular disease control. Essays in Biochemistry, v. 42, p. 105-117, 2006. https://doi.org/10.1042/bse0420105

Peeri, M.; Habibian, M.; Azarbayjani, M. A.; Hedayati, M. Protective effect of aerobic exercise against L-NAME induced kidney damage in rats. Archives of Industrial Hygiene and Toxicology, v. 64, p. 229-235, 2013. https://doi.org/10.2478/10004-1254-64-2013-2260

Pérez-Torres, I.; Roque, P.; Hafidi, M. E.; Diaz, E.; Baños, G. Association of renal damage and oxidative stress in a rat model of metabolic syndrome. Influence of gender. Free Radical Research, v. 43, no. 8, p. 761-771, 2009. https://doi.org/10.1080/10715760903045296

Punaro, G. R.; Maciel, F. R.; Rodrigues, A. M.; Rogero, M. M.; Bogsan, C. S. B.; Oliveira, M. N.; Ihara, S. S. M.; Araujo, S. R. R.; Sanches, T. R. C.; Andrade, L. C.; Higa, E. M. S. Kefir administration reduced progression of renal injury in STZ-diabetic rats by lowering oxidative stress. Nitric Oxide, v. 37, p. 53-60, 2014. https://doi.org/10.1016/j.niox.2013.12.012

Riazi, S.; Maric, C.; Ecelbarger, C. A. 17-β Estradiol attenuates streptozotocin-induced diabetes and regulates the expression of renal sodium transporters. Kidney International, v. 69, no. 3, p. 471-480, 2006. https://doi.org/10.1038/sj.ki.5000140

Rodrigues, A. M.; Bergamaschi, C. T.; Araújo, R. C.; Mouro, M. G. Effects of training and nitric oxide on diabetic nephropathy progression in type I diabetic rats. Experimental Biology and Medicine, v. 236, no. 10, p. 1180-1187, 2011. https://doi.org/10.1258%2Febm.2011.011005

Saito, T.; Sumithran, E.; Glasgow, E. F.; Atkins, R. C. The enhancement of aminonucleoside nephrosis by the coadministration of protamine. Kidney International, v. 32, p. 691-699, 1987.

Saleh, M. A.; Miguel, C. D.; Stevens, D. I.; Carmines, P. K.; Pollock, D. M.; Pollock, J. S. Free radical scavenging decreases endothelin-1 excretion and glomerular albumin permeability during type 1 diabetes. Physiological Reports, v. 4, n. 4, e13055, 2016. https://doi.org/10.14814/phy2.13055

Sharma, K.; McGowan, T. A. TGF-β in diabetic kidney disease: Role of novel signaling pathways. Cytokine & Growth Factor Reviews, v. 11, no. 1/2, p. 115-123, 2000. https://doi.org/10.1016/S1359-6101(99)00035-0

Shih, W.; Hines, W. H.; Neilson E. G. Effects of cyclosporin A on the development of imune-mediated interstitial nephritis. Kidney International, v. 33, no. 6, p. 1113-1118, 1988. https://doi.org/10.1038/ki.1988.119

Silva, K. A. S.; Luiz, R. S.; Rampaso, R. R.; Abreu, N. P.; Moreira, E. D.; Mostarda, C. T.; Angelis, K. D.; Teixeira, V. P. C.; Irigoyen, M. C.; Schor, N. Previous exercise training has a beneficial effect on renal and cardiovascular function in a model of diabetes. PLoS ONE, v. 7, no. 11, e48826, 2012. https://doi.org/10.1371/journal.pone.0048826

Sofue, T.; Kiyomoto, H.; Kobori, H.; Urushihara, M.; Nishijima, Y.; Kaifu, K.; Hara, T.; Matsumoto, S.; Ichimura, A.; Ohsaki, H.; Hitomi, H.; Kawachi, H.; Hayden, M. R.; Whaley-Connell, A.; Sowers, J. R.; Ito, S.; Kohno, M.; Nishiyama, A. Early treatment with Olmesartan prevents juxtamedullary glomerular podocyte injury and the onset of microalbuminuria in type 2 diabetic rats. American Journal of Hypertension, v. 25, no. 5, p. 604-611, 2012. https://doi.org/10.1038/ajh.2012.1

Souza, S. B. C.; Flues, K.; Paulini, J.; Mostarda, C.; Rodrigues, B.; Souza, L. E.; Irigoyen, M. C.; Angelis, K. D. Role of exercise training in cardiovascular autonomic dysfunction and mortality in diabetic ovariectomized rats. Hypertension, v. 50, no. 4, p. 786-791, 2007. https://doi.org/10.1161/HYPERTENSIONAHA.107.095000

Suarez, M. L. G.; Thomas, D. B.; Barisoni, L.; Fornoni, A. Diabetic nephropathy: Is it time yet for routine kidney biopsy? World Journal Diabetes, v. 4, no. 6, p. 245-255, 2013. https://doi.org/10.4239/wjd.v4.i6.245

Trevisan, R.; Barnes, D. J.; Viberti, G. Pathogenesis of diabetic nephropathy. In: Pickup, J. C.; Williams, J. Text book of diabetes. 2. ed. Oxford: Blackwell Science, 1997.

Volpini, R. A.; Silva, C. G. A.; Costa, R. S.; Coimbra, T. M. Effect of enalapril and losartan on the events that precede diabetic nephropathy in rats. Diabetes/Metabolism Research and Reviews, v. 19, p. 43-51, 2003.

Wang, J. H.; Ren, K.; Sun, W. G.; Zhao, L.; Zhong, H. S.; Xu, K. Effects of iodinated contrast agents on renal oxygenation level determined by blood oxygenation level dependent magnetic resonance imaging in rabbit models of type 1and type 2 diabetic nephropathy. BMC Nephrology, 15:140, 2014. https://doi.org/10.1186/1471-2369-15-140

Zambon, L.; Duarte, F. O.; Freitas, L. F.; Scarmagnani, F. R. R.; Dâmaso, A.; Duarte, A. C. G. O.; Sene-Fiorese, M. Efeitos de dois tipos de treinamento de natação sobre a adiposidade e o perfil lipídico de ratos obesos exógenos. Revista de Nutrição, v. 22, no. 5, p. 707-715, 2009. https://doi.org/10.1590/S1415-52732009000500011


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