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Chronic dietary supplementation with kynurenic acid, a neuroactive metabolite of tryptophan, decreased body weight without negative influence on densitometry and mandibular bone biomechanical endurance in young rats


Autoři: Ewa Tomaszewska aff001;  Siemowit Muszyński aff002;  Damian Kuc aff003;  Piotr Dobrowolski aff004;  Krzysztof Lamorski aff005;  Katarzyna Smolińska aff006;  Janine Donaldson aff007;  Izabela Świetlicka aff002;  Maria Mielnik-Błaszczak aff003;  Piotr Paluszkiewicz aff008;  Jolanta Parada-Turska aff009
Působiště autorů: Department of Animal Physiology, University of Life Sciences in Lublin, Lublin, Poland aff001;  Department of Biophysics, University of Life Sciences in Lublin, Lublin, Poland aff002;  Department of Developmental Age Stomatology, Chair of Developmental Age Stomatology, Medical University of Lublin, Lublin, Poland aff003;  Department of Comparative Anatomy and Anthropology, Maria Curie-Sklodowska University, Lublin, Poland aff004;  Bohdan Dobrzański Institute of Agrophysics of the Polish Academy of Sciences, Lublin, Poland aff005;  Department of Surgery and Surgical Nursing, Medical University of Lublin, Lublin, Poland aff006;  School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa aff007;  Department of General, Oncological and Metabolic Surgery, Institute of Haematology and Transfusion Medicine, Warszawa, Poland aff008;  Department of Rheumatology and Connective Tissue Diseases, Medical University of Lublin, Lublin, Poland aff009
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0226205

Souhrn

Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan. KYNA naturally occurs in breast milk and its content increases with lactation, indicating the role of neonatal nutrition in general growth with long-term health effects. KYNA is also an antagonist of ionotropic glutamate receptors expressed in bone cells. The aim of this study was to establish the effects of chronic KYNA supplementation on bone homeostasis in young rats, using mandible as a model bone. Female and male newborn Wistar rats were divided into control and KYNA-administered groups until 60 days of age (25x101 mg/L or 25x102 mg/L in drinking water). Hemimandibles were subjected to densitometry, computed tomography analysis and mechanical testing. Rats supplemented with KYNA at both doses showed a decrease in body weight. There were no effects of KYNA administration and mandible histomorphometry. In males, a significant quadratic effect (P < 0.001) was observed in the densitometry of the hemimandible, where BMD increased in the group supplemented with 2.5x101 mg/L of KYNA. Analysis of mechanical tests data showed that when fracture forces were corrected for bone geometry and rats body weight the improvement of bone material properties was observed in male and female rats supplemented with lower dose of KYNA. This study showed that chronic supplementation with KYNA may limit weight gain in the young, without adversely affecting the development of the skeleton.

Klíčová slova:

Body weight – Water resources – Mandible – Glutamate – Bone fracture – Tryptophan – Bone and joint mechanics


Zdroje

1. Badawy AA. Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects. Int J Tryptophan Res. 2017;1: 1178646917691938.

2. Turski WA, Schwarcz R. On the disposition of intrahippocampally injected kynurenic acid in the rat. Exp Brain Res. 1988;71: 563–567. doi: 10.1007/bf00248748 3416969

3. Noguchi T, Minatogawa Y, Okuno E, Nakatan M, Morimoto M, Kido R. Purification and characterization of kynurenine-2-oxoglutarate aminotransferase from the liver, brain and small intestine of rats. Biochem J. 1975;151: 399–406. doi: 10.1042/bj1510399 1218085

4. Kuc D, Zgrajka W, Parada-Turska J, Urbanik-Sypniewska T, Turski WA. Micromolar concentration of kynurenic acid in rat small intestine. Amino Acids 2008;35: 503–505. doi: 10.1007/s00726-007-0631-z 18235993

5. Le Floc’h N, Otten W, Merlot E. Tryptophan metabolism, from nutrition to potential therapeutic applications. Amino Acids 2010;41: 1195–1205. doi: 10.1007/s00726-010-0752-7 20872026

6. Paluszkiewicz P, Zgrajka W, Saran T, Schabowski J, Valverde Piedra JL, Fedkiv O, et al. High concentration of kynurenic acid in bile and pancreatic juice. Amino Acids 2009;37: 637–641. doi: 10.1007/s00726-008-0183-x 18836681

7. Stążka J, Luchowski P, Wielosz M, Kleinrok Z, Urbańska EM. Endothelium-dependent production and liberation of kynurenic acid by rat aortic rings exposed to L-kynurenine. Eur J Pharmacol. 2002;448: 133–137. doi: 10.1016/s0014-2999(02)01943-x 12144932

8. Buchli R, Alberati-Giani D, Malherbe P, Köhler C, Broger C, Cesura AM. Cloning and functional expression of a soluble form of kynurenine/a-aminoadipate aminotransferase from rat kidney. J Biol Chem. 1995;270: 29330–29335. doi: 10.1074/jbc.270.49.29330 7493966

9. Milart P, Paluszkiewicz P, Dobrowolski P, Tomaszewska E, Smolińska K, Dębińska I, et al. Kynurenic acid as the neglected ingredient of commercial baby formulas. Sci Rep. 2019;9: 6108. doi: 10.1038/s41598-019-42646-4 30988385

10. Turski MP, Turska M, Zgrajka W, Kuc D, Turski WA. Presence of kynurenic acid in food and honeybee products. Amino Acids 2009;36: 75–80. doi: 10.1007/s00726-008-0031-z 18231708

11. Samad N, Yasmin F, Naheed S, Bari A. Z, Ayaz M. M, Zaman A. Serum levels of leptin, zinc and tryptophan in obese subjects with sleep deficits. Pak J Pharm Sci. 2017; 30: 1431–1438. 29043993

12. Chen Y, Guillemin GJ. Kynurenine pathway metabolites in humans: disease and healthy States. Int J Tryptophan Res. 2009;2: 1–19. doi: 10.4137/ijtr.s2097 22084578

13. Stone TW, Stoy N, Darlington LG. An expanding range of targets for kynurenine metabolites of tryptophan. Trends Pharmacol Sci. 2013;34: 136–143. doi: 10.1016/j.tips.2012.09.006 23123095

14. Moriyama Y, Hayashi M, Yamada H, Yatsushiro S, Ishio S, Yamamoto A. Synaptic-like microvesicles, synaptic vesicle counterparts in endocrine cells, are involved in a novel regulatory mechanism for the synthesis and secretion of hormones. J Exp Biol. 2000;203: 117–125. 10600680

15. Tapiero H, Mathé G, Couvreur P, Tew KD. Glutamine and glutamate. Biomed Pharmacother. 2002;56: 446–457. doi: 10.1016/s0753-3322(02)00285-8 12481981

16. Espinosa L, Itzstein C, Cheynel H, Delmas PD, Chenu C. Active NMDA glutamate receptors are expressed by mammalian osteoclasts. J Physiol. 1999;518: 47–53. doi: 10.1111/j.1469-7793.1999.0047r.x 10373688

17. Taylor AF. Osteoblastic glutamate receptor function regulates bone formation and resorption. J Muskuloskel Neuron Interact. 2002;2: 285–290.

18. Mason DJ. Glutamate signaling and its potential application to tissue engineering of bone. Eur Cells Mater. 2004;7: 12–26.

19. Vidal C, Li W, Santner-Nanan B, Lim CK, Guillemin GJ, Ball HJ, et al. The kynurenine pathway of tryptophan degradation is activated during osteoblastogenesis. Stem Cells 2015;33: 111–121. doi: 10.1002/stem.1836 25186311

20. Dauncey MJ, Bicknell RJ. Nutrition and neurodevelopment: mechanisms of developmental dysfunction and disease in later life. Nutr Res Rev. 1999;12: 231–253. doi: 10.1079/095442299108728947 19087453

21. Neu J, Hauser N, Douglas-Escobar M. Postnatal nutrition and adult health programming. Sem Fetal Neonatal Med. 2007;12: 78–86.

22. Śliwa E. 2-Oxoglutaric acid administration diminishes fundectomy-induced osteopenia in pigs. J Anim Physiol Anim Nutr. 2010;94: e86–e95.

23. Kalaska B, Pawlak K, Domaniewski T, Oksztulska-Kolanek E, Znorko B, Roszczenko A, Rogalska J, et al. Elevated levels of peripheral kynurenine decrease bone strength in rats with chronic kidney disease. Front Physiol. 2017;8: 836. doi: 10.3389/fphys.2017.00836 29163188

24. Fejes A, Párdutz A, Toldi J, Vécsei L. Kynurenine metabolites and migraine: experimental studies and therapeutic perspectives. Curr Neuropharmacol. 2011;9: 376–387. doi: 10.2174/157015911795596621 22131946

25. Glavin GB, Pinsky C. Kynurenic acid attenuates experimental ulcer formation and basal gastric acid secretion in rats. Res Commun Chem Pathol Pharmacol. 1989;64: 111–119. 2748994

26. Wejksza K, Rzeski W, Turski WA. Kynurenic acid protects against the homocysteine-induced impairment of endothelial cells. Pharmacol Rep. 2009;61: 751–756. doi: 10.1016/s1734-1140(09)70130-6 19815960

27. Jiang GZ, Matsumoto H, Hori M, Gunji A, Hakozaki K, Akimoto Y, et al. Correlation among geometric, densitometric, and mechanical properties in mandible and femur of osteoporotic rats. J Bone Miner Metab. 2008;26: 130–137. doi: 10.1007/s00774-007-0811-7 18301968

28. Ridler TW, Calvard S. Picture thresholding using an iterative selection method. IEEE Trans Syst Man Cybern. 1978;8: 630–632.

29. Hsu PY, Tsai MT, Wang SP, Chen YJ, Wu J, Hsu JT. Cortical bone morphological and trabecular bone microarchitectural changes in the mandible and femoral neck of ovariectomized rats. PLoS ONE 2016;11: e0154367. doi: 10.1371/journal.pone.0154367 27127909

30. Bozzini C, Picasso E, Champin G, Bozzini CE, Alippi RM. Effect of physical consistency of food on the biomechanical behaviour of the mandible in the growing rat. Eur J Oral Sci. 2015;123: 350–355. doi: 10.1111/eos.12209 26336977

31. Muszyński S, Kwiecień M, Tomaszewska E, Świetlicka I, Dobrowolski P, Kasperek K, et al. Effect of caponization on performance and quality characteristics of long bones in Polbar chickens. Poult Sci. 2017;96: 491–500. doi: 10.3382/ps/pew301 27591270

32. Bianchi ML. Osteoporosis in children and adolescents. Bone 2007;41: 486–495. doi: 10.1016/j.bone.2007.07.008 17706477

33. Heaney RP, Abrams S, Dawson-Hughes B, Looker A, Marcus R, Matkovic V, et al. Peak bone mass. Osteoporos Int. 2000;11: 985–1009. doi: 10.1007/s001980070020 11256898

34. Williams B, Waddington D, Murray DH, Farquharson C. Bone strength during growth: influence of growth rate on cortical porosity and mineralization. Calcif Tissue Int. 2004;74: 236–245. doi: 10.1007/s00223-002-2124-0 14517713

35. Turski WA, Małaczewska J, Marciniak S, Bednarski J, Turski MP, Jabłoński M, et al. On the toxicity of kynurenic acid in vivo and in vitro. Pharmacol Rep. 2014;66: 1127–1133. doi: 10.1016/j.pharep.2014.07.013 25443745

36. Isales C, Ding K, Bollag W, McGee-Lawrence M, Hill W, Shi W, et al. Kynurenic acid a tryptophan metabolite induces bone loss in mice. Innov Aging 2018;2(Suppl 1): 100–101.

37. Agudelo LZ, Ferreira DMS, Cervenka I, Bryzgalova G, Dadvar S, Jannig PR, et al. Kynurenic acid and Gpr35 regulate adipose tissue energy homeostasis and inflammation. Cell Metab. 2018;27: 378–392. doi: 10.1016/j.cmet.2018.01.004 29414686

38. Rios-Avila L, Nijhout HF, Reed MC, Sitren HS, Gregory JF 3rd. A mathematical model of tryptophan metabolism via the kynurenine pathway provides insights into the effects of vitamin B-6 deficiency, tryptophan loading, and induction of tryptophan 2,3-dioxygenase on tryptophan metabolites. J Nutr. 2013;43: 1509–1519.

39. Magni P, Dozio E, Galliera E, Ruscica M, Corsi MM. Molecular aspects of adipokine-bone. Curr Mo. Med. 2010;10: 522–532.

40. Reid IR. Fat and bone. Arch Biochem Biophys. 2010; 503; 20–27. doi: 10.1016/j.abb.2010.06.027 20599663

41. Horner K, Devlin H, Alsop CW, Hodgkinson IM, Adams JE. Mandibular bone mineral density as a predictor of skeletal osteoporosis. Br J Radiol. 1996;68: 1019–1025.

42. Jespen KJ, Silva MJ, Vashishth D, Guo XE, van der Meulen MCH. Establishing biomechanical mechanisms in mouse models: practical guidelines for systematically evaluating phenotypic changes in the diaphyses of long bones. J Bone Miner Res. 2015;30: 951–966. doi: 10.1002/jbmr.2539 25917136

43. Poormasjedi-Meibod M-S, Hartwell R, Taghi Kilani R, Ghahary A. Anti-Scarring Properties of Different Tryptophan Derivatives. PLoS ONE 2014;93: e91955.

44. Nowicka-Stążka P, Langner E, Turski W, Rzeski W, Parada-Turska J. Quinaldic acid in synovial fluid of patients with rheumatoid arthritis and osteoarthritis and its effect on synoviocytes in vitro. Pharmacol Rep. 2018;70: 277–283. doi: 10.1016/j.pharep.2017.09.010 29477035

45. Lezón CE, Pintos PM, Bozzini C, Romero AA, Casavalle P, Friedman SM, et al. Mechanical mandible competence in rats with nutritional growth retardation. Arch Oral Biol. 2017;80: 10–17. doi: 10.1016/j.archoralbio.2017.03.009 28363114

46. Wang S, Ye L; Li M; Zhan H; Ye R; Yu Li Y, et al. Effects of growth hormone and functional appliance on mandibular growth in an adolescent rat model. Angle Orthod. 2018;88: 624–631. doi: 10.2319/120417-829.1 29708397

47. Wang J, Simonavicius N, Wu X, Swaminath G, Reagan J, Tian H, et al. Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. J Biol Chem. 2006;281: 22021–22028. doi: 10.1074/jbc.M603503200 16754668

48. Brakspear KS, Mason DJ. Glutamate signaling in bone. Front Endocrinol. 2012;3: 97.

49. Tavafoghi M, Cerruti M. The role of amino acids in hydroxyapatite mineralization. J R Soc Interface 2016;13: 20160462. doi: 10.1098/rsif.2016.0462 27707904

50. Lin TH, Yang RS, Tang CH, Wu MY, Fu WM. Regulation of the maturation of osteoblasts and osteoclastogenesis by glutamate. Eur J Pharmacol. 2008;589: 37–44. doi: 10.1016/j.ejphar.2008.04.060 18538763

51. Śliwa E, Kowalik S, Tatara MR, Krupski W, Majcher P, Łuszczewska-Sierakowska I, et al. Effect of alpha-ketoglutarate given to pregnant sows on the development of the humerus and femur in newborns. Bull Vet Inst Pulawy 2005;49: 117–120.

52. Tomaszewska E, Dobrowolski P, Wydrych J. Postnatal administration of 2-oxoglutaric acid improves articular and growth plate cartilages and bone tissue morphology in pigs prenatally treated with dexamethasone. J Physiol Pharmacol. 2012;63: 547–554. 23211309

53. Tomaszewska E, Dobrowolski P, Bieńko M, Prost Ł, Szymańczyk S, Zdybel A. Effects of 2-oxoglutaric acid on bone morphometry, densitometry, mechanics, and immunohistochemistry in 9-month-old boars with prenatal dexamethasone-induced osteopenia. Connect Tissue Res. 2015;56: 483–492. doi: 10.3109/03008207.2015.1069822 26305209

54. Tomaszewska E, Dobrowolski P, Prost Ł, Hułas-Stasiak M, Muszyński S, Blicharski T. The effect of supplementation of glutamine precursor on the growth plate, articular cartilage and cancellous bone in fundectomy-induces osteopenic bone. J Vet Med Sci. 2016;76: 563–571.

55. Suva LJ, Gaddy D. Back to the future: Evaluation of the role of glutamate in bone cells. Calcif Tissue Int. 2016;99: 112–113. doi: 10.1007/s00223-016-0135-5 27061091

56. Forrest CM, Mackay GM, Oxford L, Stoy N, Stone TW, Darlington LG. Kynurenine pathway metabolism in patients with osteoporosis after 2 years of drug treatment. Clin Exp Pharmacol Physiol. 2006;33: 1078–1087. doi: 10.1111/j.1440-1681.2006.04490.x 17042918

57. Michalowska M, Znorko B, Kaminski E, Oksztulska-Kolanek E, Pawlak D. New insights into tryptophan and its metabolites in the regulation of bone metabolism. J Physiol Pharmacol. 2015;66: 779–791. 26769827

58. Forrest CM, Kennedy A, Stone TW, Stoy N, Darlington LG. Kynurenine and neopterin levels in patients with rheumatoid arthritis and osteoporosis during drug treatment. Adv Exp Med Biol. 2003;527: 287–295. doi: 10.1007/978-1-4615-0135-0_32 15206742

59. Dinçel E, Özkan Y, Şüküroğlu M, Özsoy H, Sepici Dinçel A. Evaluation of tryptophan/kynurenine pathway relevance with immune system biomarkers of low energy trauma hip fractures in osteoporotic patients. Arch Rheumatol. 2017;32: 203–208. doi: 10.5606/ArchRheumatol.2017.6216 30375548

60. Pernow Y, Thorén M, Sääf M, Fernholm R, Anderstam B, Hauge EM, et al. Associations between amino acids and bone mineral density in men with idiopathic osteoporosis. Bone 2010;47: 959–965. doi: 10.1016/j.bone.2010.08.017 20813216

61. Badawy AA, Dougherty DM. Assessment of the human kynurenine pathway: comparisons and clinical implications of ethnic and gender differences in plasma tryptophan, kynurenine metabolites, and enzyme expressions at baseline and after acute tryptophan loading and depletion. Int J Tryptophan Res. 2016;9: 31–49. doi: 10.4137/IJTR.S38189 27547036

62. Kim BJ, Hamrick MW, Yoo HJ, Lee SH, Kim SJ, Koh JM, et al. The detrimental effects of kynurenine, a tryptophan metabolite, on human bone metabolism. J Clin Endocrinol Metab. 2019;104: 2334–2342. doi: 10.1210/jc.2018-02481 30715395


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