Bulaşıcı Olmayan Hastalıkların Patofizyolojisinde Arjininin Rolü

Yıl 2022, Cilt: 3 Sayı: 3, 144 - 152, 30.07.2022

Betül Sukan Karaçağıl Yasemin Akdevelioğlu

Öz

Çoğu kronik olan “bulaşıcı olmayan hastalıklar (BOH)
her yıl 41 milyon insanın ölümünden sorumludur ve bu
sayı tüm dünyadaki ölüm nedenlerinin %71’ini oluşturmaktadır. Türkiye’de ise 2020 yılında BOH’lardan kaynaklanan ölüm oranı %89 olup, kardiyovasküler hastalıklar
(%36,8), tümörler (%18,4) ve solunum sistemi hastalıkları (%12,9) ölüm sebeplerinin ilk üçünü oluşturmaktadır.
Yüksek ölüm oranları BOH’ları küresel bir endişe kaynağı
haline getirmektedir.
BOH’ların oluşmasında genetik ve fizyolojik faktörlerin
yanı sıra çevresel ve davranışsal faktörler de etkilidir. Çevresel ve davranışsal faktörler değiştirilebilir nitelik taşıdığı
için BOH riskinin azaltılmasında etkili stratejiler sunmaktadır. Bu nedenle besin öğesi ve kronik hastalık ilişkisinin
aydınlatılması BOH’ların tanı ve tedavisinde önem arz
etmektedir.
Bir besin öğesi olan arjinin, şartlı esansiyel bir aminoasittir
ve birçok hastalığın patofizyolojisi ile yakından ilişkilidir.
Arjinin ve türev moleküllerinin veya metabolizmasında
rol alan enzimler ve metabolitlerinin bazı BOH’lar için
biyobelirteç veya teröpatik bir hedef olabileceği düşünülmektedir. Literatürde güncel ve tartışmalı bir konu olan
arjinin-kronik hastalık ilişkisinin netleştirilmesi için daha
fazla bilimsel çalışmaya ihtiyaç duyulmaktadır.
Bu derleme ile arjinin ile bazı kronik hastalıkların ilişkisi
güncel çalışmalar ile tartışılarak, BOH’ların önlenmesi ve
tedavisi için gelecekteki çalışmalara ışık tutmak amaçlanmaktadır.

Anahtar Kelimeler

Bulaşıcı Olmayan Hastalıklar, Kronik Hastalıklar, Arjinin

Kaynakça

• 1. Organization WH. Non-communicable diseases Progress Monitor, 2020 [Internet]. Available at: https://www.who.int/publications/i/item/ncd-progress-monitor-2020
• 2. Kluge HHP, Wickramasinghe K, Rippin HL, Mendes R, Peters DH, Kontsevaya A, et al. lütfenPrevention and control of non-communicable diseases in the COVID-19 response. Lancet. 2020;395(10238):1678–80.
• 3. Noncommunicable diseases [Internet]. 2021. Available at: https://www.who. int/news-room/fact-sheets/detail/noncommunicable-diseases
• 4. Türkiye İstatistik Kurumu, 2019 [Internet]. Available at: https://data.tuik.gov.tr/Bulten/Index?p=Olum-ve-Olum-Nedeni-Istatistikleri-2019-33710
• 5. Budreviciute A, Damiati S, Sabir DK, Onder K, Schuller-Goetzburg P, Plakys G, et al. Management and Prevention Strategies for Non-communicable Diseases (NCDs) and Their Risk Factors. Front Public Heal. 2020 Nov 26;8:788.
• 6. Ulusal Gıda Kompozisyon Veri Tabanı, 2020 [Internet]. Available at: http://www.turkomp.gov.tr/component_result-153
• 7. McNeal CJ, Meininger CJ, Reddy D, Wilborn CD, Wu G. Safety and effectiveness of Arginine in adults. J Nutr. 2016;146(12):2587-93.
• 8. Zou S, Wang X, Liu P, Ke C, Xu S. Arginine metabolism and deprivation in cancer therapy. Biomed Pharmacother. 2019;118:1-11.
• 9. Szefel J, Danielak A, Kruszewski WJ. Metabolic pathways of L-arginine and therapeutic consequences in tumors. Adv Med Sci. 2019;64(1):104–10.
• 10. Mangoni AA, Rodionov RN, Mcevoy M, Zinellu A, Carru C, Sotgia S. New horizons in arginine metabolism, ageing and chronic disease states. Age Ageing. 2019;48(6):776–82.
• 11. Farah C, Michel LYM, Balligand JL. Nitric oxide signalling in cardiovascular health and disease. Nat Rev Cardiol. 2018;15(5):292–316.
• 12. Gambardella J, Khondkar W, Morelli MB, Wang X, Santulli G, Trimarco V. Arginine and endothelial function. Biomedicines. 2020;8(8):1-25.
• 13. Sardu C, Gambardella J, Morelli MB, Wang X, Marfella R, Santulli G. Hypertension, thrombosis, kidney failure, and diabetes: Is covid-19 an endothelial disease? a comprehensive evaluation of clinical and basic evidence. J Clin Med. 2020;9(5):1-22.
• 14. Reizine F, Lesouhaitier M, Gregoire M, Pinceaux K, Gacouin A, Maamar A, et al. SARS-CoV-2-Induced ARDS Associates with MDSC Expansion, Lymphocyte Dysfunction, and Arginine Shortage. J Clin Immunol.2021;41(3):515–25. 15. Fiorentino G, Coppola A, Izzo R, Annunziata A, Bernardo M, Lombardi A, et al. Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of the first interim analysis. EClinicalMedicine. 2021;40:1-7.
• 16. Zarezadeh M, Emami MR, Kord-Varkane H, Mousavi SM, Alizadeh H, As-baghi O, et al. The effect of oral L-arginine supplementation on asymmetric dimethylarginine levels: A systematic review and meta-analysis of randomized clinical trials. Adv Integr Med. 2020;7(2):61–6.
• 17. Tsikas D, Wu G. Homoarginine, arginine, and relatives: analysis, metabolism, transport, physiology, and pathology. Amino Acids. 2015;47(9):1697–702.
• 18. Zinellu A, Paliogiannis P, Carru C, Mangoni AA. Homoarginine and all-cause mortality: A systematic review and meta-analysis. Eur J Clin Invest. 2018;48(8):1-9.
• 19. Papageorgiou N, Androulakis E, Papaioannou S, Antoniades C, Tousoulis D. Homoarginine in the shadow of asymmetric dimethylarginine: from nitric oxide to cardiovascular disease. Amino Acids. 2015;47(9):1741–50.
• 20. Adejare A, Oloyo A, Anigbogu C, Jaja S. l-arginine Supplementation Increased Only Endothelium-Dependent Relaxation in Sprague-Dawley Rats Fed a High-Salt Diet by Enhancing Abdominal Aorta Endothelial Nitric Oxide Synthase Gene Expression. Clin Med Insights Cardiol. 2020;14:1-9.
• 21. Ellis AC, Mehta T, Nagabooshanam VA, Dudenbostel T, Locher JL, Crowe-White KM. Daily 100% watermelon juice consumption and vascular function among postmenopausal women: A randomized controlled trial. Nutr Metab Cardiovasc Dis. 2021;31(10):2959-68.
• 22. Salmani M, Alipoor E, Navid H, Farahbakhsh P, Yaseri M, Imani H. Effect of l-arginine on cardiac reverse remodeling and quality of life in patients with heart failure. Clin Nutr. 2021;40(5):3037-44.
• 23. Qiu F, Huang J, Sui M. Targeting arginine metabolism pathway to treat arginine-dependent cancers. Cancer Lett. 2015 Aug 1;364(1):1–7.
• 24. Zou Z, Hu X, Luo T, Ming Z, Chen X, Xia L, et al. Naturally-occurring spinosyn A and its derivatives function as argininosuccinate synthase activator and tumor inhibitor. Nat Commun. 2021;12(1):1-15.
• 25. Locke M, Ghazaly E, Freitas MO, Mitsinga M, Lattanzio L, Lo Nigro C, et al. Inhibition of the Polyamine Synthesis Pathway Is Synthetically Lethal with Loss of Argininosuccinate Synthase 1. Cell Rep.2016;16(6):1604–13.
• 26. Szabo C. Gasotransmitters in cancer: From pathophysiology to experimental therapy. Nat Rev Drug Discov. 2016;15(3):185–203.
• 27. Zhang Y, Chung SF, Tam SY, Leung YC, Guan X. Arginine deprivation as a strategy for cancer therapy: An insight into drug design and drug combination. Cancer Lett. 2021;502:58–70.
• 28. Fried, R., Carlton, R. M., Fried, D. A. (2021). Cancer Cells: Evidence-Based Strategies to Slow Cancer Progression. 1st ed. Cambirdge:Academic Press;2021, p. 25–111.
• 29. Philiph R, Campbell E, Wheatley DN. Arginine deprivation, growth inhibition and tumour cell death: 2. Enzymatic degradation of arginine in normal and malignant cell cultures. Br J Cancer. 2003;88(4):613-23.
• 30. Buijs N, van Bokhorst-de van der Schueren MA, Langius JA, Leemans CR, Kuik DJ, Vermeulen MA, van Leeuwen PA. Perioperative arginine-supplemented nutrition in malnourished patients with head and neck cancer improves long-term survival. Am J Clin Nutr. 2010;92(5):1151-6.
• 31. Zhao H, Zhao H, Wang Y, Jing H, Ding Q, Xue J. Randomized clinical trial of arginine-supplemented enteral nutrition versus standard enteral nutrition in patients undergoing gastric cancer surgery. J Cancer Res Clin Oncol. 2013;139(9):1465-70.
• 32. Scott JA, Maarsingh H, Holguin F, Grasemann H. Arginine Therapy for Lung Diseases. Front Pharmacol. 2021;12:1-7.
• 33. Zinellu A, Fois AG, Mangoni AA, Paliogiannis P, Sotgiu E, Zinellu E, et al. Systemic concentrations of asymmetric dimethylarginine (ADMA) in chronic obstructive pulmonary disease (COPD): state of the art. Amino Acids. 2018;50(9):1169–76.
• 34. Menzies-Gow A, Mansur AH, Brightling CE. Clinical utility of fractional exhaled nitric oxide in severe asthma management. Eur Respir J. 2020;55(3):1-13.
• 35. den Berg MPM, Kurhade SH, Maarsingh H, Erceg S, Hulsbeek IR, Boekema PH, et al. Pharmacological Screening Identifies SHK242 and SHK277 as Novel Arginase Inhibitors with Efficacy against Allergen-Induced Airway Narrowing In Vitro and In Vivo. J Pharmacol Exp Ther. 2020;374(1):62 - 73.
• 36. Brown MB, Kempf A, Collins CM, Long GM, Owens M, Gupta S, Hellman Y, Wong V, Farber M, Lahm T. A prescribed walking regimen plus arginine supplementation improves function and quality of life for patients with pulmonary arterial hypertension: a pilot study. Pulmonary circulation. 2017;8(1):1-12.