The effects of branched chain amino acid supplement on kidney tissue of exercising rats
Keywords:
resistance exercise, kidney damage, caspase 3, branched chain amino acids, KIM-1
Abstract
Introduction: One of the supplements used in exercise programs are branched-chain amino acids (BCAAs), which are preferred because of their effect on the regeneration of muscle protein synthesis. However, due to their properties, BCAAs increase their amount in the blood in a short time. In this case the result may increase the workload of the kidneys. Based on the information, this study investigated the effects of resistance exercise and BCAA supplements on kidney tissue. Methods: A total of 24 Wistar Albino male rats were equally divided into 4 groups: Control, BCAA, Exercise and Exercise + BCAA. In the six-week study, resistance swimming exercise was applied to the exercise groups. BCAA supplementation was given to BCAA groups at 2.5 mg/kg doses before exercise. At the end of the study, histological, immunochemical and RT-PCR analyzes were performed. Results: As a result of the findings, it was found that the use of BCAA supplements together with exercise caused tubular necrosis (p=0.002). There was a significant increase in caspase 3 IHC staining findings in BCAA and Exercise + BCAA groups compared to the control group (p=0.011; p=0.02). In addition, KIM-1 expression levels were higher in the Exercise group than in all other groups (p=0.004; p = 0.003; p=0.008). Conclusion: As a result, BCAA consumption with resistance exercise caused damage to kidney tissue.
References
1) Booth FW, Roberts CK, Laye MJ. Lack of exercise is a major cause of chronic diseases. Compr Physiol. 2012;2(2):1143-211. doi: 10.1002/cphy.c110025.
2) Ardıç F. Exercise prescription. Turk J Phys Med Rehab. 2014;60 (Suppl. 2):S1-S8. doi: 10.5152/tftrd.2014.25665.
3) Daenen L, Varkey E, Kellmann M, Nijs J. Exercise, not to exercise, or how to exercise in patients with chronic pain? Applying science to practice. Clin J Pain. 2015;31(2):108-14. doi: 10.1097/AJP.0000000000000099.
4) Idorn M, Thor Straten P. Exercise and cancer: from "healthy" to "therapeutic"? Cancer Immunol Immunother. 2017;66(5):667-71. doi: 10.1007/s00262-017-1985-z.
5) Kerksick CM, Wilborn CD, Roberts MD, Smith-Ryan A, Kleiner SM, Jäger R, et al. ISSN exercise & sports nutrition review update: research & recommendations. J Int Soc Sports Nutr. 2018;15(1):38. doi: 10.1186/s12970-018-0242-y.
6) Bifari F, Nisoli E. Branched-chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view. Br J Pharmacol. 2017;174(11):1366-77. doi: 10.1111/bph.13624.
7) Goron A, Moinard C. Amino acids and sport: a true love story? Amino Acids. 2018;50(8):969-80. doi: 10.1007/s00726-018-2591-x.
8) Pitkänen HT, Oja SS, Rusko H, Nummela A, Komi PV, Saransaari P, et al. Leucine supplementation does not enhance acute strength or running performance but affects serum amino acid concentration. Amino Acids. 2003;25(1):85-94. doi: 10.1007/s00726-002-0343-3.
9) Wolfe RR. Branched-chain amino acids and muscle protein synthesis in humans: myth or reality? J Int Soc Sports Nutr. 2017;14(1):1-7. doi: 10.1186/s12970-017-0184.
10) Holeček M. Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements. Nutr Metab (Lond). 2018;15:33. doi: 10.1186/s12986-018-0271-1.
11) Priante G, Gianesello L, Ceol M, Del Prete D, Anglani F. Cell death in the kidney. Int J Mol Sci. 2019;20(14):3598. doi: 10.3390/ijms20143598.
12) Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, et al. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem. 1998;273(7):4135-42. doi: 10.1074/jbc.273.7.4135.
13) van Timmeren MM, van den Heuvel MC, Bailly V, Bakker SJ, van Goor H, Stegeman CA. Tubular kidney injury molecule-1 (KIM-1) in human renal disease. J Pathol. 2007;212(2):209-17. doi: 10.1002/path.2175.
14) Lu M, Zhang X, Zheng D, Jiang X, Chen Q. Branched-chain amino acids supplementation protects streptozotocin-induced insulin secretion and the correlated mechanism. Biofactors. 2015;41(2):127-33. doi: 10.1002/biof.1188.
15) Vieira R, Haebisch H, Kokubun E, Hell NS, Curi R. Sistema de natação para exercício físico de ratos. Arq Biol Tecnol. 1988;31(3):387-94.
16) Campos-Ferraz PL, Bozza T, Nicastro H, Lancha AH Jr. Distinct effects of leucine or a mixture of the branched-chain amino acids (leucine, isoleucine, and valine) supplementation on resistance to fatigue, and muscle and liver-glycogen degradation, in trained rats. Nutrition. 2013;29(11-12):1388-94. doi: 10.1016/j.nut.2013.05.003.
17) Büyük B, Demirci T, Adalı Y, Eroğlu HA. ¿Puede el líquido amniótico ser una solución alternativa de conservación de órganos para el almacenamiento renal en frío? Rev Nefrol Diál Traspl. 2020;40(1):14-24.
18) Kandemir FM, Yildirim S, Kucukler S, Caglayan C, Mahamadu A, Dortbudak MB. Therapeutic efficacy of zingerone against vancomycin-induced oxidative stress, inflammation, apoptosis, and aquaporin 1 permeability in rat kidney. Biomed Pharmacother. 2018;105:981-91. doi: 10.1016/j.biopha.2018.06.048.
19) Doğanlar ZB, Uzun M, Ovali MA, Dogan A, Ongoren G, Doğanlar O. Melatonin attenuates caspase-dependent apoptosis in the thoracic aorta by regulating element balance and oxidative stress in pinealectomised rats. Appl Physiol Nutr Metab. 2019;44(2):153-63. doi: 10.1139/apnm-2018-0205.
20) Lin X, Jiang C, Luo Z, Qu S. Protective effect of erythropoietin on renal injury induced in rats by four weeks of exhaustive exercise. BMC Nephrol. 2013;14:130. doi: 10.1186/1471-2369-14-130.
21) Spada TC, Silva JMRD, Francisco LS, Marçal LJ, Antonangelo L, Zanetta DMT, et al. High intensity resistance training causes muscle damage and increases biomarkers of acute kidney injury in healthy individuals. PLoS One. 2018;13(11):e0205791. doi: 10.1371/journal.pone.0205791.
22) Baird MF, Graham SM, Baker JS, Bickerstaff GF. Creatine-kinase- and exercise-related muscle damage implications for muscle performance and recovery. J Nutr Metab. 2012;2012:960363. doi: 10.1155/2012/960363.
23) Sorichter S, Mair J, Koller A, Calzolari C, Huonker M, Pau B, et al. Release of muscle proteins after downhill running in male and female subjects. Scand J Med Sci Sports. 2001;11(1):28-32. doi: 10.1034/j.1600-0838.2001.011001028.x.
24) Tsatalas T, Giakas G, Spyropoulos G, Sideris V, Lazaridis S, Kotzamanidis C, et al. The effects of eccentric exercise-induced muscle damage on running kinematics at different speeds. J Sports Sci. 2013;31(3):288-98. doi: 10.1080/02640414.2012.729135.
25) Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, et al.; Nomenclature Committee on Cell Death 2009. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ. 2009;16(1):3-11. doi: 10.1038/cdd.2008.150.
26) Mooren FC, Krüger K. Exercise, autophagy, and apoptosis. Prog Mol Biol Transl Sci. 2015;135:407-22. doi: 10.1016/bs.pmbts.2015.07.023.
27) Gladden LB. Lactate metabolism: a new paradigm for the third millennium. J Physiol. 2004;558(Pt 1):5-30. doi: 10.1113/jphysiol.2003.058701.
28) Lindinger MI. Potassium regulation during exercise and recovery in humans: implications for skeletal and cardiac muscle. J Mol Cell Cardiol. 1995;27(4):1011-22. doi: 10.1016/0022-2828(95)90070-5.
29) Thomson MN, Schneider W, Mutig K, Ellison DH, Kettritz R, Bachmann S. Patients with hypokalemia develop WNK bodies in the distal convoluted tubule of the kidney. Am J Physiol Renal Physiol. 2019;316(2):F292-F300. doi: 10.1152/ajprenal.00464.2018.
30) Jiao C, Chen W, Tan X, Liang H, Li J, Yun H, et al. Ganoderma lucidum spore oil induces apoptosis of breast cancer cells in vitro and in vivo by activating caspase-3 and caspase-9. J Ethnopharmacol. 2020;247:112256. doi: 10.1016/j.jep.2019.112256.
31) Bildik A, Bayar İ. Kanserde Apoptotik Yolakların İnhibisyonu. Turkiye Klinikleri J Vet Sci. 2018;9(2):42-51. doi: 10.5336/vetsci.2018-62141.
32) Goldar S, Khaniani MS, Derakhshan SM, Baradaran B. Molecular mechanisms of apoptosis and roles in cancer development and treatment. Asian Pac J Cancer Prev. 2015;16(6):2129-44. doi: 10.7314/apjcp.2015.16.6.2129.
33) Viana LR, Tobar N, Busanello ENB, Marques AC, de Oliveira AG, Lima TI, et al. Leucine-Rich diet induces a shift in tumour metabolism from glycolytic towards oxidative phosphorylation, reducing glucose consumption and metastasis in walker-256 tumour-bearing rats. Sci Rep. 2019;9:15529. doi: 10.1038/s41598-019-52112-w.
34) Rautureau GJ, Day CL, Hinds MG. Intrinsically disordered proteins in bcl-2 regulated apoptosis. Int J Mol Sci. 2010;11(4):1808-24. doi: 10.3390/ijms11041808.
35) Yin W, Kumar T, Lai Z, Zeng X, Kanaan HD, Li W, et al. Kidney injury molecule-1, a sensitive and specific marker for identifying acute proximal tubular injury, can be used to predict renal functional recovery in native renal biopsies. Int Urol Nephrol. 2019;51(12):2255-65. doi: 10.1007/s11255-019-02311-1.
2) Ardıç F. Exercise prescription. Turk J Phys Med Rehab. 2014;60 (Suppl. 2):S1-S8. doi: 10.5152/tftrd.2014.25665.
3) Daenen L, Varkey E, Kellmann M, Nijs J. Exercise, not to exercise, or how to exercise in patients with chronic pain? Applying science to practice. Clin J Pain. 2015;31(2):108-14. doi: 10.1097/AJP.0000000000000099.
4) Idorn M, Thor Straten P. Exercise and cancer: from "healthy" to "therapeutic"? Cancer Immunol Immunother. 2017;66(5):667-71. doi: 10.1007/s00262-017-1985-z.
5) Kerksick CM, Wilborn CD, Roberts MD, Smith-Ryan A, Kleiner SM, Jäger R, et al. ISSN exercise & sports nutrition review update: research & recommendations. J Int Soc Sports Nutr. 2018;15(1):38. doi: 10.1186/s12970-018-0242-y.
6) Bifari F, Nisoli E. Branched-chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view. Br J Pharmacol. 2017;174(11):1366-77. doi: 10.1111/bph.13624.
7) Goron A, Moinard C. Amino acids and sport: a true love story? Amino Acids. 2018;50(8):969-80. doi: 10.1007/s00726-018-2591-x.
8) Pitkänen HT, Oja SS, Rusko H, Nummela A, Komi PV, Saransaari P, et al. Leucine supplementation does not enhance acute strength or running performance but affects serum amino acid concentration. Amino Acids. 2003;25(1):85-94. doi: 10.1007/s00726-002-0343-3.
9) Wolfe RR. Branched-chain amino acids and muscle protein synthesis in humans: myth or reality? J Int Soc Sports Nutr. 2017;14(1):1-7. doi: 10.1186/s12970-017-0184.
10) Holeček M. Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements. Nutr Metab (Lond). 2018;15:33. doi: 10.1186/s12986-018-0271-1.
11) Priante G, Gianesello L, Ceol M, Del Prete D, Anglani F. Cell death in the kidney. Int J Mol Sci. 2019;20(14):3598. doi: 10.3390/ijms20143598.
12) Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, et al. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem. 1998;273(7):4135-42. doi: 10.1074/jbc.273.7.4135.
13) van Timmeren MM, van den Heuvel MC, Bailly V, Bakker SJ, van Goor H, Stegeman CA. Tubular kidney injury molecule-1 (KIM-1) in human renal disease. J Pathol. 2007;212(2):209-17. doi: 10.1002/path.2175.
14) Lu M, Zhang X, Zheng D, Jiang X, Chen Q. Branched-chain amino acids supplementation protects streptozotocin-induced insulin secretion and the correlated mechanism. Biofactors. 2015;41(2):127-33. doi: 10.1002/biof.1188.
15) Vieira R, Haebisch H, Kokubun E, Hell NS, Curi R. Sistema de natação para exercício físico de ratos. Arq Biol Tecnol. 1988;31(3):387-94.
16) Campos-Ferraz PL, Bozza T, Nicastro H, Lancha AH Jr. Distinct effects of leucine or a mixture of the branched-chain amino acids (leucine, isoleucine, and valine) supplementation on resistance to fatigue, and muscle and liver-glycogen degradation, in trained rats. Nutrition. 2013;29(11-12):1388-94. doi: 10.1016/j.nut.2013.05.003.
17) Büyük B, Demirci T, Adalı Y, Eroğlu HA. ¿Puede el líquido amniótico ser una solución alternativa de conservación de órganos para el almacenamiento renal en frío? Rev Nefrol Diál Traspl. 2020;40(1):14-24.
18) Kandemir FM, Yildirim S, Kucukler S, Caglayan C, Mahamadu A, Dortbudak MB. Therapeutic efficacy of zingerone against vancomycin-induced oxidative stress, inflammation, apoptosis, and aquaporin 1 permeability in rat kidney. Biomed Pharmacother. 2018;105:981-91. doi: 10.1016/j.biopha.2018.06.048.
19) Doğanlar ZB, Uzun M, Ovali MA, Dogan A, Ongoren G, Doğanlar O. Melatonin attenuates caspase-dependent apoptosis in the thoracic aorta by regulating element balance and oxidative stress in pinealectomised rats. Appl Physiol Nutr Metab. 2019;44(2):153-63. doi: 10.1139/apnm-2018-0205.
20) Lin X, Jiang C, Luo Z, Qu S. Protective effect of erythropoietin on renal injury induced in rats by four weeks of exhaustive exercise. BMC Nephrol. 2013;14:130. doi: 10.1186/1471-2369-14-130.
21) Spada TC, Silva JMRD, Francisco LS, Marçal LJ, Antonangelo L, Zanetta DMT, et al. High intensity resistance training causes muscle damage and increases biomarkers of acute kidney injury in healthy individuals. PLoS One. 2018;13(11):e0205791. doi: 10.1371/journal.pone.0205791.
22) Baird MF, Graham SM, Baker JS, Bickerstaff GF. Creatine-kinase- and exercise-related muscle damage implications for muscle performance and recovery. J Nutr Metab. 2012;2012:960363. doi: 10.1155/2012/960363.
23) Sorichter S, Mair J, Koller A, Calzolari C, Huonker M, Pau B, et al. Release of muscle proteins after downhill running in male and female subjects. Scand J Med Sci Sports. 2001;11(1):28-32. doi: 10.1034/j.1600-0838.2001.011001028.x.
24) Tsatalas T, Giakas G, Spyropoulos G, Sideris V, Lazaridis S, Kotzamanidis C, et al. The effects of eccentric exercise-induced muscle damage on running kinematics at different speeds. J Sports Sci. 2013;31(3):288-98. doi: 10.1080/02640414.2012.729135.
25) Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, et al.; Nomenclature Committee on Cell Death 2009. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ. 2009;16(1):3-11. doi: 10.1038/cdd.2008.150.
26) Mooren FC, Krüger K. Exercise, autophagy, and apoptosis. Prog Mol Biol Transl Sci. 2015;135:407-22. doi: 10.1016/bs.pmbts.2015.07.023.
27) Gladden LB. Lactate metabolism: a new paradigm for the third millennium. J Physiol. 2004;558(Pt 1):5-30. doi: 10.1113/jphysiol.2003.058701.
28) Lindinger MI. Potassium regulation during exercise and recovery in humans: implications for skeletal and cardiac muscle. J Mol Cell Cardiol. 1995;27(4):1011-22. doi: 10.1016/0022-2828(95)90070-5.
29) Thomson MN, Schneider W, Mutig K, Ellison DH, Kettritz R, Bachmann S. Patients with hypokalemia develop WNK bodies in the distal convoluted tubule of the kidney. Am J Physiol Renal Physiol. 2019;316(2):F292-F300. doi: 10.1152/ajprenal.00464.2018.
30) Jiao C, Chen W, Tan X, Liang H, Li J, Yun H, et al. Ganoderma lucidum spore oil induces apoptosis of breast cancer cells in vitro and in vivo by activating caspase-3 and caspase-9. J Ethnopharmacol. 2020;247:112256. doi: 10.1016/j.jep.2019.112256.
31) Bildik A, Bayar İ. Kanserde Apoptotik Yolakların İnhibisyonu. Turkiye Klinikleri J Vet Sci. 2018;9(2):42-51. doi: 10.5336/vetsci.2018-62141.
32) Goldar S, Khaniani MS, Derakhshan SM, Baradaran B. Molecular mechanisms of apoptosis and roles in cancer development and treatment. Asian Pac J Cancer Prev. 2015;16(6):2129-44. doi: 10.7314/apjcp.2015.16.6.2129.
33) Viana LR, Tobar N, Busanello ENB, Marques AC, de Oliveira AG, Lima TI, et al. Leucine-Rich diet induces a shift in tumour metabolism from glycolytic towards oxidative phosphorylation, reducing glucose consumption and metastasis in walker-256 tumour-bearing rats. Sci Rep. 2019;9:15529. doi: 10.1038/s41598-019-52112-w.
34) Rautureau GJ, Day CL, Hinds MG. Intrinsically disordered proteins in bcl-2 regulated apoptosis. Int J Mol Sci. 2010;11(4):1808-24. doi: 10.3390/ijms11041808.
35) Yin W, Kumar T, Lai Z, Zeng X, Kanaan HD, Li W, et al. Kidney injury molecule-1, a sensitive and specific marker for identifying acute proximal tubular injury, can be used to predict renal functional recovery in native renal biopsies. Int Urol Nephrol. 2019;51(12):2255-65. doi: 10.1007/s11255-019-02311-1.
Published
2022-06-15
How to Cite
1.
Aydeğer C, Hüseyin Avni Eroğlu. The effects of branched chain amino acid supplement on kidney tissue of exercising rats. Rev Nefrol Dial Traspl. [Internet]. 2022Jun.15 [cited 2024Dec.27];42(2):124-33. Available from: http://revistarenal.org.ar/index.php/rndt/article/view/790
Section
Original Article
Copyright (c) 2022 Revista de Nefrología, Diálisis y Trasplante
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
