Künt Toraks Travmasında Trimetilamin N-Oksit (TMAO) Düzeylerinin Değerlendirilmesi: Deneysel Bir Çalışma
Year 2024,
Volume: 34 Issue: 3, 327 - 331, 30.06.2024
Fatma Şengül
,
Fikret Akyürek
,
Bahadir Ozturk
,
Hüsamettin Vatansev
,
Aysegül Bayır
,
Hasan Kara
,
Muslu Kazım Körez
Abstract
Arka plan/Amaç: Toraks travmaları akciğer kontüzyonundan multi-organ yaralanmalarına kadar yaşamı tehdit eden problemlere neden olabilirken, akut akciğer yaralanması (ALI) ve akut solunum sıkıntısı sendromu (ARDS), travmatik yaralanmaların yaygın komplikasyonlarıdır. Künt toraks travmasının şiddetini belirlemek ve inflamatuar süreci takip etmek için biyokimyasal bir belirteç oluşturmak önemlidir. Bu çalışmada, tavşanlarda düşük, orta ve yüksek enerjili künt toraks travması modelinde serum Trimetilamin N-oksit (TMAO) düzeylerini ölçmek ve bu metabolitin tanısal değerini araştırmak amaçlanmıştır.
Gereç ve Yöntemler: Bu çalışmada, 27 Yeni Zelanda tavşanı dört gruba ayrılmıştır [kontrol, düşük enerjili travma grubu, orta enerjili travma grubu ve yüksek enerjili travma grubu]. Kan örnekleri toraks travmasından sonraki 1., 12. ve 24. saatlerde alınmıştır.
Bulgular: TMAO için hem gruplar içinde hem de gruplar arasında istatistiksel olarak anlamlı bir fark bulunmuştur (p<0.0001).
Sonuç: TMAO seviyeleri özellikle travmayı takip eden ilk saatte yükselmekte, 12 ve 24. Saatlerde ilk ate kıyasla düşmektedir (orta ve yüksek enerjili travma gruplarında). Bu bilgi potansiyel olarak travmanın hem şiddetinin hem de zamanlamasının bir göstergesi olabilir. Farklı enerji seviyeleri uygulanarak oluşturulan künt torasik travmaya bağlı ALI’de, TMAO seviyeleri gruplar arasında değişiklik göstermiş ve travmanın hem zamanlaması hem de şiddetiyle ilişkilendirilmiştir. Bu bulgular, TMAO düzeylerinin travmanın prognozunu değerlendirmede ve inflamatuar süreci izlemede değerli olabileceği önerisini desteklemektedir.
Ethical Statement
Çalışma Helsinki Bildirgesi'ne uygun olarak yürütülmüş ve Selçuk Üniversitesi Deneysel Tıp Araştırma ve Uygulama Merkezi Etik Kurulu tarafından onaylanmıştır (protokol kodu 2022-39 ve onay tarihi 30/09/2022).
References
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- Matuschak GM, Lechner AJ. Acute lung injury and the acute respiratory distress syndrome: pathophysiology and treatment. Missouri Medicine. 2010;107(4):252-8.
- Wu J, Sheng L, Wang S, Li Q, Zhang M, Xu S, et al. Analysis of clinical risk factors associated with the prognosis of severe multiple-trauma patients with acute lung injury. The Journal of Emergency Medicine. 2012;43(3):407-12. doi.org/10.1016/j.jemermed.2009.05.024
- Shanmugham M, Bellanger S, Leo CH. Gut-Derived Metabolite, Trimethylamine-N-oxide (TMAO) in Cardio-Metabolic Diseases: Detection, Mechanism, and Potential Therapeutics. Pharmaceuticals. 2023;16(4):504. doi.org/10.3390/ph16040504
- Canyelles M, Borràs C, Rotllan N, Tondo M, Escolà-Gil JC, Blanco-Vaca F. Gut Microbiota-Derived TMAO: A Causal Factor Promoting Atherosclerotic Cardiovascular Disease? International Journal of Molecular Sciences. 2023;24(3):1940. doi.org/10.3390/ijms24031940
- Gatarek P, Kaluzna-Czaplinska J. Trimethylamine N-oxide (TMAO) in human health. EXCLI Journal : Experimental and Clinical Sciences. 2021;20:301-19. doi.org/10.17179%2Fexcli2020-3239
- Oktaviono YH, Dyah Lamara A, Saputra PBT, Arnindita JN, Pasahari D, Saputra ME, et al. The roles of trimethylamine-N-oxide in atherosclerosis and its potential therapeutic aspect: A literature review. Biomolecules and Biomedicine. 2023;23(6):936-48. doi.org/10.17305%2Fbb.2023.8893
- Zhang Y, Wang Y, Ke B, Du J. TMAO: how gut microbiota contributes to heart failure. Translational Research. 2021;228:109-25. doi.org/10.1016/j.trsl.2020.08.007
- Fretts AM, Hazen SL, Jensen P, Budoff M, Sitlani CM, Wang M, et al. Association of Trimethylamine N-oxide and metabolites with mortality in older adults. JAMA Network Open. 2022;5(5):e2213242-e. doi.org/10.1001/jamanetworkopen.2022.13242
- Li C, Zhu L, Dai Y, Zhang Z, Huang L, Wang TJ, et al. Diet-induced high serum levels of trimethylamine-N-oxide enhance the cellular inflammatory response without exacerbating acute intracerebral hemorrhage injury in mice. Oxidative Medicine and Cellular Longevity. 2022;2022. doi.org/10.1155/2022/1599747
- Kaya H, Kafalı ME, Aydın K, Şahin M, Duran A, Bayır A, et al. A Novel Experimental Bilateral Blunt Chest Trauma Model on Rabbits and its Effects in Lung. Journal of Academic Emergency Medicine. 2011;10(3). doi.org/10.5152/jaem.2011.020
- Calfee CS, Eisner MD, Ware LB, Thompson BT, Parsons PE, Wheeler AP, et al. Trauma-associated lung injury differs clinically and biologically from acute lung injury due to other clinical disorders. Critical Care Medicine. 2007;35(10):2243-50. doi.org/10.1097/01.ccm.0000280434.33451.87
- Raghavendran K, Notter RH, Davidson BA, Helinski JD, Kunkel SL, Knight PR. Lung contusion: inflammatory mechanisms and interaction with other injuries. Shock. 2009;32(2):122-30. doi.org/10.1097/SHK.0b013e31819c385c
- Ganie FA, Lone H, Lone GN, Wani ML, Singh S, Dar AM, et al. Lung Contusion: A Clinico-Pathological Entity with Unpredictable Clinical Course. Bulletin of Emergency & Trauma. 2013;1(1):7-16.
- Li T, Chen Y, Gua C, Li X. Elevated Circulating Trimethylamine N-Oxide Levels Contribute to Endothelial Dysfunction in Aged Rats through Vascular Inflammation and Oxidative Stress. . Frontiers in Physiology. 2017;8:350. doi.org/10.3389/fphys.2017.00350
- Zeisel SH, Warrier M. Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease. Annual Review of Nutrition. 2017;37:157-81.
- Brunt VE, Gioscia-Ryan RA, Casso AG, VanDongen NS, Ziemba BP, Sapinsley ZJ, et al. Trimethylamine-N-Oxide Promotes Age-Related Vascular Oxidative Stress and Endothelial Dysfunction in Mice and Healthy Humans. Hypertension. 2020;76(1):101-12. doi.org/10.1161/hypertensionaha.120.14759
- Sun X, Jiao X, Ma Y, Liu Y, Zhang L, He Y, et al. Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome. Biochemical and Biophysical Research Communications. 2016;481(1):63-70. doi.org/10.1016/j.bbrc.2016.11.017
- Fioretto JR, Campos FJ, Ronchi CF, Ferreira AL, Kurokawa CS, Carpi MF, et al. Effects of inhaled nitric oxide on oxidative stress and histopathological and inflammatory lung injury in a saline-lavaged rabbit model of acute lung injury. Respiratory Care. 2012;57(2):273-81. doi.org/10.4187/respcare.01289
- Kinross JM, Alkhamesi N, Barton RH, Silk DB, Yap IK, Darzi AW, et al. Global metabolic phenotyping in an experimental laparotomy model of surgical trauma. Journal of Proteome Research. 2011;10(1):277-87. doi.org/10.1021/pr1003278
- Schindler CR, Lustenberger T, Woschek M, Störmann P, Henrich D, Radermacher P, et al. Severe traumatic brain injury (TBI) modulates the kinetic profile of the inflammatory response of markers for neuronal damage. Journal of Clinical Medicine. 2020;9(6):1667. doi.org/10.3390/jcm9061667
- Zhen J, Zhou Z, He M, Han HX, Lv EH, Wen PB, et al. The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases. Frontiers in Endocrinology (Lausanne). 2023;14:1085041. doi.org/10.3389%2Ffendo.2023.1085041
- Tu R, Xia J. Stroke and vascular cognitive impairment: the role of intestinal microbiota metabolite TMAO. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders). 2024;23(1):102-121. doi.org/10.2174/1871527322666230203140805
- Liu Y, Dai M. Trimethylamine N-Oxide Generated by the Gut Microbiota Is Associated with Vascular Inflammation: New Insights into Atherosclerosis. Mediators of Inflammation. 2020;2020:4634172. doi.org/10.1155/2020/4634172
- Matsuzawa Y, Nakahashi H, Konishi M, Sato R, Kawashima C, Kikuchi S, et al. Microbiota-derived Trimethylamine N-oxide Predicts Cardiovascular Risk After STEMI. Scientific Reports. 2019;9(1):11647. doi.org/10.1038/s41598-019-48246-6
- Janeiro MH, Ramírez MJ, Milagro FI, Martínez JA, Solas M. Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target. Nutrients. 2018;10(10):1398. doi.org/10.3390/nu10101398
Evaluation of Trimethylamine N-Oxide (TMAO) Levels in Blunt Thoracic Trauma: An Experimental Study
Year 2024,
Volume: 34 Issue: 3, 327 - 331, 30.06.2024
Fatma Şengül
,
Fikret Akyürek
,
Bahadir Ozturk
,
Hüsamettin Vatansev
,
Aysegül Bayır
,
Hasan Kara
,
Muslu Kazım Körez
Abstract
Background/Aims: Thoracic traumas cause life-threatening problems ranging from lung contusion to multiorgan injuries, while acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common complications of traumatic injuries. It is important to establish a biochemical marker to determine the severity of blunt thoracic trauma and to follow the inflammatory process. To measure serum Trimethylamine N-oxide (TMAO) levels and to investigate the diagnostic value of this metabolite in a low, medium, and high energy blunt thoracic trauma model in rabbits.
Material and methods: In this study, 27 New Zealand rabbits were divided four groups [control, low energy trauma group, medium energy trauma group, and high energy trauma group]. Blood samples were obtained at 1st, 12th and 24th hour after thoracic trauma.
Results: There has been a statistically significant difference found both within groups and between groups for TMAO (p<0.0001).
Conclusions: TMAO levels are particularly elevated in the first hour following trauma, decreasing at 12 and 24 hours compared to the first hour (in the medium and high energy trauma groups). This information could potentially serve as an indicator of both the severity and timing of trauma. In blunt thoracic trauma-induced ALI created by applying different energy levels, TMAO levels varied among groups and were associated with both the timing and severity of the trauma. These findings support the suggestion that TMAO levels could be valuable in assessing the prognosis of trauma and monitoring the inflammatory process.
Ethical Statement
The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the University of Selçuk, Experimental Medicine Applications and Research Centre (protocol code 2022-39 and date of approval 30/09/2022) for studies.
References
- Mouawad NJ, Paulisin J, Hofmeister S, Thomas MB. Blunt thoracic aortic injury – concepts and management. Journal of Cardiothoracic Surgery. 2020;15(1):62. doi.org/10.1186/s13019-020-01101-6
- Matuschak GM, Lechner AJ. Acute lung injury and the acute respiratory distress syndrome: pathophysiology and treatment. Missouri Medicine. 2010;107(4):252-8.
- Wu J, Sheng L, Wang S, Li Q, Zhang M, Xu S, et al. Analysis of clinical risk factors associated with the prognosis of severe multiple-trauma patients with acute lung injury. The Journal of Emergency Medicine. 2012;43(3):407-12. doi.org/10.1016/j.jemermed.2009.05.024
- Shanmugham M, Bellanger S, Leo CH. Gut-Derived Metabolite, Trimethylamine-N-oxide (TMAO) in Cardio-Metabolic Diseases: Detection, Mechanism, and Potential Therapeutics. Pharmaceuticals. 2023;16(4):504. doi.org/10.3390/ph16040504
- Canyelles M, Borràs C, Rotllan N, Tondo M, Escolà-Gil JC, Blanco-Vaca F. Gut Microbiota-Derived TMAO: A Causal Factor Promoting Atherosclerotic Cardiovascular Disease? International Journal of Molecular Sciences. 2023;24(3):1940. doi.org/10.3390/ijms24031940
- Gatarek P, Kaluzna-Czaplinska J. Trimethylamine N-oxide (TMAO) in human health. EXCLI Journal : Experimental and Clinical Sciences. 2021;20:301-19. doi.org/10.17179%2Fexcli2020-3239
- Oktaviono YH, Dyah Lamara A, Saputra PBT, Arnindita JN, Pasahari D, Saputra ME, et al. The roles of trimethylamine-N-oxide in atherosclerosis and its potential therapeutic aspect: A literature review. Biomolecules and Biomedicine. 2023;23(6):936-48. doi.org/10.17305%2Fbb.2023.8893
- Zhang Y, Wang Y, Ke B, Du J. TMAO: how gut microbiota contributes to heart failure. Translational Research. 2021;228:109-25. doi.org/10.1016/j.trsl.2020.08.007
- Fretts AM, Hazen SL, Jensen P, Budoff M, Sitlani CM, Wang M, et al. Association of Trimethylamine N-oxide and metabolites with mortality in older adults. JAMA Network Open. 2022;5(5):e2213242-e. doi.org/10.1001/jamanetworkopen.2022.13242
- Li C, Zhu L, Dai Y, Zhang Z, Huang L, Wang TJ, et al. Diet-induced high serum levels of trimethylamine-N-oxide enhance the cellular inflammatory response without exacerbating acute intracerebral hemorrhage injury in mice. Oxidative Medicine and Cellular Longevity. 2022;2022. doi.org/10.1155/2022/1599747
- Kaya H, Kafalı ME, Aydın K, Şahin M, Duran A, Bayır A, et al. A Novel Experimental Bilateral Blunt Chest Trauma Model on Rabbits and its Effects in Lung. Journal of Academic Emergency Medicine. 2011;10(3). doi.org/10.5152/jaem.2011.020
- Calfee CS, Eisner MD, Ware LB, Thompson BT, Parsons PE, Wheeler AP, et al. Trauma-associated lung injury differs clinically and biologically from acute lung injury due to other clinical disorders. Critical Care Medicine. 2007;35(10):2243-50. doi.org/10.1097/01.ccm.0000280434.33451.87
- Raghavendran K, Notter RH, Davidson BA, Helinski JD, Kunkel SL, Knight PR. Lung contusion: inflammatory mechanisms and interaction with other injuries. Shock. 2009;32(2):122-30. doi.org/10.1097/SHK.0b013e31819c385c
- Ganie FA, Lone H, Lone GN, Wani ML, Singh S, Dar AM, et al. Lung Contusion: A Clinico-Pathological Entity with Unpredictable Clinical Course. Bulletin of Emergency & Trauma. 2013;1(1):7-16.
- Li T, Chen Y, Gua C, Li X. Elevated Circulating Trimethylamine N-Oxide Levels Contribute to Endothelial Dysfunction in Aged Rats through Vascular Inflammation and Oxidative Stress. . Frontiers in Physiology. 2017;8:350. doi.org/10.3389/fphys.2017.00350
- Zeisel SH, Warrier M. Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease. Annual Review of Nutrition. 2017;37:157-81.
- Brunt VE, Gioscia-Ryan RA, Casso AG, VanDongen NS, Ziemba BP, Sapinsley ZJ, et al. Trimethylamine-N-Oxide Promotes Age-Related Vascular Oxidative Stress and Endothelial Dysfunction in Mice and Healthy Humans. Hypertension. 2020;76(1):101-12. doi.org/10.1161/hypertensionaha.120.14759
- Sun X, Jiao X, Ma Y, Liu Y, Zhang L, He Y, et al. Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome. Biochemical and Biophysical Research Communications. 2016;481(1):63-70. doi.org/10.1016/j.bbrc.2016.11.017
- Fioretto JR, Campos FJ, Ronchi CF, Ferreira AL, Kurokawa CS, Carpi MF, et al. Effects of inhaled nitric oxide on oxidative stress and histopathological and inflammatory lung injury in a saline-lavaged rabbit model of acute lung injury. Respiratory Care. 2012;57(2):273-81. doi.org/10.4187/respcare.01289
- Kinross JM, Alkhamesi N, Barton RH, Silk DB, Yap IK, Darzi AW, et al. Global metabolic phenotyping in an experimental laparotomy model of surgical trauma. Journal of Proteome Research. 2011;10(1):277-87. doi.org/10.1021/pr1003278
- Schindler CR, Lustenberger T, Woschek M, Störmann P, Henrich D, Radermacher P, et al. Severe traumatic brain injury (TBI) modulates the kinetic profile of the inflammatory response of markers for neuronal damage. Journal of Clinical Medicine. 2020;9(6):1667. doi.org/10.3390/jcm9061667
- Zhen J, Zhou Z, He M, Han HX, Lv EH, Wen PB, et al. The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases. Frontiers in Endocrinology (Lausanne). 2023;14:1085041. doi.org/10.3389%2Ffendo.2023.1085041
- Tu R, Xia J. Stroke and vascular cognitive impairment: the role of intestinal microbiota metabolite TMAO. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders). 2024;23(1):102-121. doi.org/10.2174/1871527322666230203140805
- Liu Y, Dai M. Trimethylamine N-Oxide Generated by the Gut Microbiota Is Associated with Vascular Inflammation: New Insights into Atherosclerosis. Mediators of Inflammation. 2020;2020:4634172. doi.org/10.1155/2020/4634172
- Matsuzawa Y, Nakahashi H, Konishi M, Sato R, Kawashima C, Kikuchi S, et al. Microbiota-derived Trimethylamine N-oxide Predicts Cardiovascular Risk After STEMI. Scientific Reports. 2019;9(1):11647. doi.org/10.1038/s41598-019-48246-6
- Janeiro MH, Ramírez MJ, Milagro FI, Martínez JA, Solas M. Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target. Nutrients. 2018;10(10):1398. doi.org/10.3390/nu10101398