sdü tıp fak derg

Medical Journal of Süleyman Demirel University

2602-2109

Süleyman Demirel Üniversitesi

10.17343/sdutfd.928607

Clinical Sciences

Klinik Tıp Bilimleri

PROPIONYLCARNITINE AND FREE CARNITINE ARE NEW BIOMARKERS IN THE FOLLOW-UP PERIOD OF MUCOPOLYSACCARIDOSIS TO SCREEN OXIDATIVE STRESS

MUKOPOLİSAKKARİDOZ HASTALARININ TAKİP SÜRECİNDE OKSİDATİF STRESİ TARAMADA YENİ BİYOBELİRTEÇLER, PROPİONİLKARNİTİN VE SERBEST KARNİTİN

https://orcid.org/0000-0001-5446-4140

İnci

Aslı

GAZİ ÜNİVERSİTESİ

https://orcid.org/0000-0002-4989-221X

Olgac

Asburce

GAZİ ÜNİVERSİTESİ

https://orcid.org/0000-0003-3805-4445

Genç Derin

Betül

GAZİ ÜNİVERSİTESİ

https://orcid.org/0000-0001-5948-188X

Biberoğlu

Gürsel

GAZİ ÜNİVERSİTESİ

https://orcid.org/0000-0002-8772-0689

Okur

İlyas

GAZİ ÜNİVERSİTESİ

https://orcid.org/0000-0001-9497-3118

Ezgü

Fatih Süheyl

GAZİ ÜNİVERSİTESİ

https://orcid.org/0000-0002-7831-3184

Tümer

Leyla

GAZİ ÜNİVERSİTESİ

12 30 2021

28 4 565 571 04 30 2021 10 21 2021

1994

Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi

ObjectiveThere is no applicable and easy procedure to screenoxidative stress in mucopolysaccaridosis (MPS)patients. The aim herein was to show the antioxidativeproperties of free carnitine (FC) and propionylcarnitine(PC) with respect to oxidative markers in MPS anduse a simple and easy method in patient follow-up.Material and MethodsFC and PC were studied as an antioxidativemarker using tandem mass spectroscopy andmalondialdehyde (MDA) was studied as an oxidativemarker in 27 MPS patients and 24 healthy volunteers.ResultsWhile the PC and FC levels were significantlydecreased, the MDA levels were higher in theMPS patients than in the healthy volunteers.Whencompared between the enzyme-treated MPS patientsand untreated MPS patients, there were no significantdifferences between the groups. MDA was found toinversely correlated with PC (r =–0.402, P=0.003).Itwas noteworthy that PC had a significant correlationwith MDA.ConclusionThe findings revealed that the affected patients hadhigher MDA levels and lower PC and FC levels,indicating an imbalance through the oxidative side. Anapplicable method of FC and PC measurement couldbe used to screen patients, considering them as newantioxidative markers in the patient follow-up periodfor the response of enzyme replacement therapy and/or antioxidant drugs.

AmaçMukopolisakkaridoz (MPS) hastalarında oksidatifstresi taramak için uygulanabilir ve kolay bir prosedürmevcut değildir. Bu çalışmada amaç, MPS'deki oksidatifbelirteçlere göre serbest karnitin (SK) ve propiyonilkarnitinin(PK) antioksidatif özelliklerini göstermekve hasta takibinde basit ve kolay bir yöntem olarakkullanmaktır.Gereç ve YöntemÇalışmaya, 27 MPS hastasında ve 24 sağlıklı gönüllüdahil edilerek bu hastalarda SK ve PK, antioksidatifbelirteç olarak tandem kütle spektroskopisi kullanılarakçalışıldı ve malondialdehit (MDA), ise oksidatifbelirteç olarak kullanıldı.BulgularMPS hastalarında, PK ve SK seviyeleri önemli ölçüdeazalırken, MDA seviyeleri sağlıklı gönüllülere göredaha yüksek bulundu. Enzim yerine koyma tedavisialan MPS hastaları ile tedavi edilmeyen MPS hastalarıkarşılaştırıldığında, gruplar arasında anlamlı bir farksaptanmadı. Çalışma, MDA'nın PK ile anlamlı orandaters orantılı olduğu bulundu (r = –0.402, P = 0.003).PK'nin MDA ile anlamlı bir korelasyona sahip olmasıdikkat çekiciydi.SonuçMPS hastalarının daha yüksek MDA düzeylerine vedaha düşük PK ve SK düzeylerine sahip olduğunugöstermiştir, buna göre MPS hastalarının oksidatifyönde bir dengesizliğe sahip olduğunu ortaya koymuştur.PK ve SK, MPS hastalarının takibinde uygulanabilirbir yöntem olabilir ve hastaların enzim yerinekoyma ve/veya antioksidan ilaçların tedavilerinin cevabınıngözlemek için yeni biyobelirteçler olarak kullanılabilir.

free carnitine mucopolysaccaridosis propionylcarnitine antioxidation MDA

mukopolisakkaridoz propionilkarnitin serbest karnitin antioksidasyon MDA

Yoktur

1. Gustavo KA,Adalisa K, Marcos RO, Luisa MB, Melissa C. Alterations in Oxidative Markers in the Cerebellum and Peripheral Organs in MPS I Mice. Cell Mol Neurobiol 2009; 29: 443–448.

2. Pereira VG, Martins AM, Micheletti C, Almeida VD. Mutational and oxidative stress analysis in patients with mucopolysaccaridosis type 1 undergoing enzyme replacement theraphy. Clin Chim Acta 2007;387:75-79.

3. Bremer J. Carnitine: Metabolism and functions. Physiol Rev 1983;63(4):1420-1480

4. Bahl JJ, Bressler R. The pharmacology of carnitine. Annu Rev Pharmacol Toxicol 1987;27:257-277

5. T Fukao, Lopaschuk GD, Mitchell GA. Pathways and control of ketone body metabolism: on the fringe of lipid biochemistry. Prostaglandins Leukot Essent Fatty Acids 2004;70: 243-251.

6. Platell C,Kong SE, McCauley R, Hall JC. Branced –chain aminoacids. J Gastroenterol Hepatol 2000;15:706-717

7. Jogl G, Hsiao YS, Tong L. Structure and function of carnitine acyltransferases. Ann N Y Acad Sci 2004;1033;17-29.

8. Gan JLF, Simmons PA, Vehige J, Willcox MDP, Garrett Q. Role of carnitine in disease. Nutr Metab (Lond) 2010;7:30.

9. Malaguarnera M. Carnitine derivatives: clinical usefullness. Curr Opin Gastroenterol 2012;28:166-176.

10. Bertelli A, Giovannini L, Galmozzi G, Bertelli AA. Protective role of propionyl carnitine in vascular disorders experimentally induced by endothelin (ET-1) serotonin and K-carrageenin. Drugs Exp Clin Res 1993;7:7–11.

11. Bertelli A, Galmozzi G, Giovannini L, Mian M. Thrombosis induced by endothelin (ET-1) and carrageenin in rats treated with indomethacin and propionyl carnitine. Drugs Exp Clin Res 1993;19:75–78.

12. Bueno R,Alvarez de Sotomayor M, Perez-Guerrero C, Gómez-Amores L, Vazquez CM, Herrera MD. L-carnitine and propionyl-L-carnitine improve endothelial dysfunction in spontaneously hypertensive rats: diﬀerent participation of NO and COX-products. Life Sci 2005;77:2082–2097

13. Bertelli A, Conte A, Ronca G, Segnini D, Yu G. Protective eﬀect of propionyl carnitine against peroxidative damage to arterial endothelium membranes. Int J Tissue React 1991;13:41–43.

14. Bertelli A, Conte A, Palmieri L, Ronca G, Segnini D, Yu G. Eﬀect of propionyl carnitine on energy charge and adenine nucleotide content of cardiac endothelial cells during hypoxia. Int J Tissue React 1991;13: 37–40

15. De Sotomayor MA, Mingorance C, Rodriguez-Rodriguez R, Marhuenda E, Herrera MD.L-carnitine and its propionate: improvement of endothelial function in SHR through superoxide dismutase-dependent mechanisms. Free Radic Res 2007;41:884–891.

16. Alvarez de Sotomayor M, Bueno R, Pérez-Guerrero C, Herrera MD. Eﬀect of L-carnitine and propionyl-L-carnitine on endothelial function of small mesenteric arteries from SHR. J Vasc Res 2007; 44:354–364.

17. Libby P. Inﬂammation in atherosclerosis. Nature 2002;420:868–874.

18. Del Rio D, Stewart AJ, Pellegrini N.A review of recent studies on Mda as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 2005;15:316–328

19. Gucciardi A, Zaramella P, Costa I, Pirillo P, Nardo D, Naturale M et al. Analysis and interpretation of acylcarnitine profiles in dried blood spot and plasma of preterm and full-term newborns. Pediatric Research 2015;77:36–47.

20.Tsikas D. Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges. Anal Biochem 2017;524:13-30

21. Hess B, Saftig P, Hartmann D, Coenen R, Lu ¨llmann-Rauch R, Goebel HH et al. Phenotype of arylsulfatase Adeﬁcient mice: relationship to human metachromatic leukodystrophy. Proc Natl Acad Sci USA 1996; 93:14821–26. doi:10.1073/ pnas.93.25.14821

22. Wu YP, Matsuda J, Kubota A, Suzuki K. Inﬁltration of hematogenous lineage cells into the demyelinating central nervous system of twitcher mice. J Neuropathol Exp Neurol 2000;59:628–639

23. German DC, Liang CL, Song T, Yazdani U, Xie C, Dietschy JM. Neurodegeneration in the Niemann-Pick C mouse: glial involvement. Neuroscience 2002;109:437–50.doi:10.1016/S03064522(01)00517-6

24. Ohmi K, Greenberg DS, Rajavel KS, Ryazantsev S, Li HH, Neufeld EF. Activated microglia in cortex of mouse models of mucopolysaccharidosis I and IIIB. Proc Natl Acad Sci USA 2003;100 :1902–1907. doi:10.1073/pnas.252784899

25. Jeyakumar M, Thomas R, Elliot-Smith E, Smith DA, Van der Spoel AC, d’Azzo A et al. Central nervous system inﬂammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. Brain 2003;126:974–987. doi:10.1093/brain/awg089.

26. Jeyakumar M, Smith DA, Williams IM, Borja MC, Neville DC, Butters TD et al. NSAIDs increase survival in the Sandhoff disease mouse: synergy with N butyldeoxynojirimycin. Ann Neurol 2004;56:642–9. doi:10.1002/ ana.202429.

27. Filippona L, Wayhs CY, Atik DM, Manfredini V, Herber S, Carvalho CG et al. DNA damage in leukocytes from pretreatment mucopolysaccharidosis type II patients; protective effect of enzyme replacement therapy. Mutation Research 2011;721:206–210

28. Signorelli SS, Fatuzzo P, Rapisarda F, Neri S, Ferrante M, Conti GO, Fallico R et al. A randomised, controlled clinical trial evaluating changes in therapeutic efficacy and oxidative parameters after treatment with propionyl L-carnitine in patients with peripheral arterial disease requiring haemodialysis. Drugs Aging 2006;23(3):263-270

29. Santo SS, Sergio N, Luigi DP, Giuseppe Ma, Margherita F, Gea OA, Roberto F, Gabriella C et al. Effect of PC on functional parameters and oxidative profile in type 2 diabetes-associated PAD. Diabetes Res Clin Pract 2006;72(3):231