Ahmet CİZMECİOGLU, Duygu ERYAVUZ ONMAZ, Huseyin Emre AYDİN, Suleyman SENTURK, Ali UNLU, Huseyin KORKMAZ, Gökhan GÜNGÖR

Akut Pankreas İltihabı Süresince Metillenmiş Arginin Rezidüleri ve İlişkili Amino Asitlerdeki Değişimler

Amaç: Enflamasyonun yayılma derecesi, akut pankreatitin (AP) şiddetini belirler. Bir tür inflamasyon mediyatörü olan metillenmiş arjinin rezidüleri (MAR), nitrik oksit seviyelerini düşürür ve vazokonstriksiyona bağlı endotel hasarına neden olur. Bu çalışma, akut pankreas iltihabı sırasında MAR ve ilişkili amino asitleri araştırmayı amaçladı. Gereç ve Yöntem: Bu prospektif, yarı deneysel çalışma, AP tanısı konan hastalar ve yaşca uyumlu bir kontrol grubu ile yürütülmüştür. Hasta örnekleri tanı anı ve iyileşme sırasında, kontrol grubunda ise çalışma sırasında alındı. Başlıca Asimetrik dimetilarjinin (ADMA), Arjinin (ARG), Sitrulin (CIT), ve ilişkili kimyasallar kütle spektrometre ile çalışıldı. Bulgular: Çalışmaya toplam 30 AP (ortalama yaş=53,3±17,8) ve 30 kontrol (ortalama yaş=53,4±18,0) dahil edildi. Hastalar şiddetli (n=22) ve şiddetli olmayan (n=8) olarak tanımlandılar. Kontrol grubuna göre hastaların ADMA düzeylerinde belirgin azalma saptanıldı (p=0,01). MAR seviyelerinde hastalık şiddeti yönünden farklılık yoktu (p>0,05). Ancak, diyabet ya da kronik böbrek hastalığı (KBH) olan hastalarda MAR seviyeleri daha yüksek oranda düşmüştü. İki kan örneklemesi arasında ARG düzeyi ve ARG/ADMA oranı artarken MAR ve CIT/ARG oranı azaldı. Sonuç: Sonuçlarımız, AP iyileşmesi ile MAR düzeylerinin düştüğünü gösterdi. Yüksek kan MAR seviyelerinde azalmanın başlaması, pankreas iltihabının iyileşmeye başlamasını gösterebilir. AP inflamasyonu diyabet veya KBH olan hastalarda daha yıkıcı olabilir.

Anahtar Kelimeler:

Akut pankreatit, Arjinin metabolizması, Asimetrik dimetilarjinin, Nitrik oksit

Alterations of Methylated Arginine Residues and Related Amino Acids During Acute Pancreatic Inflammation

Aim: The extent of the spread of inflammation determines the severity of acute pancreatitis (AP). Methylated arginine residues (MAR), a type of inflammatory mediator, reduce nitric oxide levels and cause vasoconstriction-induced endothelial damage. This study aimed to investigate MAR and related amino acids during acute pancreatic inflammation. Material and Method: This prospective, quasi-experimental study was conducted with patients diagnosed with AP and an age-matched control group. The patient samples were taken during the diagnosis and recovery time, whereas during the study for the control group. Mainly, Asymmetric dimethylarginine (ADMA), Arginine (ARG), Citrulline (CIT), and related chemicals were studied via a mass spectrometer. Results: A total of 30 patients with AP (mean age=53.3±17.8) and 30 controls (mean age=53.4±18.0) were included in the study. All patients were identified as non-severe (n=8) and severe (n=22). A decrease was detected in the patients' ADMA levels compared to the control group (p=0.01). MAR did not differ concerning disease severity (p > 0.05). However, MAR levels decreased higher in patients with diabetes or chronic kidney disease (CKD). Between the two samplings, the ARG level and ARG to ADMA ratio increased, while the MAR and CIT to ARG ratio decreased. Conclusion: Our results showed that MAR levels decreased with AP recovery. The start of a decrease in the high-level blood MAR may indicate the healing of pancreatic inflammation. AP inflammation may be more destructive in patients with diabetes or CKD.

Keywords:

Acute pancreatitis, Arginine metabolism, Asymmetric dimethylarginine, Nitric oxide,

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Teerlink T. ADMA metabolism and clearance. Vasc Med 2005;10:73-81.
Morris SM, Jr. Arginine Metabolism Revisited. J Nutr 2016;146:2579-86.
Brooks ER, Langman CB, Wang S, et al. Methylated arginine derivatives in children and adolescents with chronic kidney disease. Pediatr Nephrol 2009;24:129-34.
D'Andrea G, Gucciardi A, Giordano G, Bussone G, Leon A. Study of arginine metabolism in medication overuse chronic migraine: possible defect in NO synthesis. Neurol Sci 2022;43:2745–9.
Cinelli MA, Do HT, Miley GP, Silverman RB. Inducible nitric oxide synthase: Regulation, structure, and inhibition. Med Res Rev 2020;40:158-89.
Crockett SD, Wani S, Gardner TB, Falck-Ytter Y. Barkun AN, American Gastroenterological Association Institute Clinical Guidelines C. American Gastroenterological Association Institute Guideline on Initial Management of Acute Pancreatitis. Gastroenterology 2018;154:1096-101.
van Santvoort HC, Bakker OJ, Bollen TL, et al. A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome. Gastroenterology 2011;141:1254-63.
Mehmood A, Ullah W, Chan V, Ringold D. The Assessment of Knowledge and Early Management of Acute Pancreatitis Among Residents. Cureus 2019;11:e4389.
Singh VK, Bollen TL, Wu BU et al. An assessment of the severity of interstitial pancreatitis. Clin Gastroenterol Hepatol 2011;9:1098-103.
Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013;62:102-11.
Basit H, Ruan GJ, Mukherjee S. Ranson Criteria. StatPearls. Treasure Island;2021.
Ong Y, Shelat VG. Ranson score to stratify severity in Acute Pancreatitis remains valid - Old is gold. Expert Rev Gastroenterol Hepatol 2021;15:865-77.
Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med 2013;368:149-60.
Jacobsen DW. Homocysteine and vitamins in cardiovascular disease. Clin Chem 1998;44:1833-43.
Fu Q, Zhai Z, Wang Y, et al. NLRP3 Deficiency Alleviates Severe Acute Pancreatitis and Pancreatitis-Associated Lung Injury in a Mouse Model. Biomed Res Int 2018;2018:1294951.
Avgerinos C, Delis S, Rizos S, et al. Nutritional support in acute pancreatitis. Dig Dis 2003;21:214-9.
Trgo G, Zaja I, Bogut A et al. Association of asymmetric dimethylarginine with acute pancreatitis-induced hyperglycemia. Pancreas 2016;45:694-9.
Yuan Q, Jiang DJ, Chen QQ, et al. Role of asymmetric dimethylarginine in homocysteine-induced apoptosis of vascular smooth muscle cells. Biochem Biophys Res Commun 2007;356:880-5.
Wells SM, Holian A. Asymmetric dimethylarginine induces oxidative and nitrosative stress in murine lung epithelial cells. Am J Respir Cell Mol Biol 2007;36:520-8.
Boger RH. Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the "L-arginine paradox" and acts as a novel cardiovascular risk factor. J Nutr 2004;134:2842-7.
Boger RH, Bode-Boger SM, Szuba A, et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 1998;98:1842-7.
Zafari P, Zarifian A, Alizadeh-Navaei R, et al. Asymmetric and symmetric dimethylarginine concentration as an indicator of cardiovascular diseases in rheumatoid arthritis patients: a systematic review and meta-analysis of case-control studies. Clin Rheumatol 2020;39:127-34.
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;48:776-82.
Janes F, Cifu A, Pessa ME, et al. ADMA as a possible marker of endothelial damage. A study in young asymptomatic patients with cerebral small vessel disease. Sci Rep 2019;9:14207.
Celik M, Cerrah S, Arabul M, Akalin A. Relation of asymmetric dimethylarginine levels to macrovascular disease and inflammation markers in type 2 diabetic patients. J Diabetes Res 2014;2014:139215.