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

Year 2021, Volume: 28 Issue: 4, 565 - 571, 30.12.2021

Aslı İnci Asburce Olgac Betül Genç Derin Gürsel Biberoğlu İlyas Okur Fatih Süheyl Ezgü Leyla Tümer

https://doi.org/10.17343/sdutfd.928607

Abstract

Amaç
Mukopolisakkaridoz (MPS) hastalarında oksidatif
stresi taramak için uygulanabilir ve kolay bir prosedür
mevcut değildir. Bu çalışmada amaç, MPS'deki oksidatif
belirteçlere göre serbest karnitin (SK) ve propiyonilkarnitinin
(PK) antioksidatif özelliklerini göstermek
ve hasta takibinde basit ve kolay bir yöntem olarak
kullanmaktır.
Gereç ve Yöntem
Çalışmaya, 27 MPS hastasında ve 24 sağlıklı gönüllü
dahil edilerek bu hastalarda SK ve PK, antioksidatif
belirteç olarak tandem kütle spektroskopisi kullanılarak
çalışıldı ve malondialdehit (MDA), ise oksidatif
belirteç olarak kullanıldı.
Bulgular
MPS hastalarında, PK ve SK seviyeleri önemli ölçüde
azalırken, MDA seviyeleri sağlıklı gönüllülere göre
daha yüksek bulundu. Enzim yerine koyma tedavisi
alan MPS hastaları ile tedavi edilmeyen MPS hastaları
karşılaştırıldığında, gruplar arasında anlamlı bir fark
saptanmadı. Çalışma, MDA'nın PK ile anlamlı oranda
ters orantılı olduğu bulundu (r = –0.402, P = 0.003).
PK'nin MDA ile anlamlı bir korelasyona sahip olması
dikkat çekiciydi.
Sonuç
MPS hastalarının daha yüksek MDA düzeylerine ve
daha düşük PK ve SK düzeylerine sahip olduğunu
göstermiştir, buna göre MPS hastalarının oksidatif
yönde bir dengesizliğe sahip olduğunu ortaya koymuştur.
PK ve SK, MPS hastalarının takibinde uygulanabilir
bir yöntem olabilir ve hastaların enzim yerine
koyma ve/veya antioksidan ilaçların tedavilerinin cevabının
gözlemek için yeni biyobelirteçler olarak kullanılabilir.

Keywords

mukopolisakkaridoz, propionilkarnitin, serbest karnitin, antioksidasyon, MDA

Supporting Institution

Yoktur

Project Number

Yoktur

Thanks

Tüm hastalarımıza ve sağlık çalışanlarına teşekkür ederiz.

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

Abstract

Objective
There is no applicable and easy procedure to screen
oxidative stress in mucopolysaccaridosis (MPS)
patients. The aim herein was to show the antioxidative
properties of free carnitine (FC) and propionylcarnitine
(PC) with respect to oxidative markers in MPS and
use a simple and easy method in patient follow-up.
Material and Methods
FC and PC were studied as an antioxidative
marker using tandem mass spectroscopy and
malondialdehyde (MDA) was studied as an oxidative
marker in 27 MPS patients and 24 healthy volunteers.
Results
While the PC and FC levels were significantly
decreased, the MDA levels were higher in the
MPS patients than in the healthy volunteers.When
compared between the enzyme-treated MPS patients
and untreated MPS patients, there were no significant
differences between the groups. MDA was found to
inversely correlated with PC (r =–0.402, P=0.003).It
was noteworthy that PC had a significant correlation
with MDA.
Conclusion
The findings revealed that the affected patients had
higher MDA levels and lower PC and FC levels,
indicating an imbalance through the oxidative side. An
applicable method of FC and PC measurement could
be used to screen patients, considering them as new
antioxidative markers in the patient follow-up period
for the response of enzyme replacement therapy and/
or antioxidant drugs.

Keywords

free carnitine, mucopolysaccaridosis, propionylcarnitine, antioxidation, MDA

Project Number

Yoktur

References

• 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