Amyotrofik lateral sklerozda antioksidan savunma bozukluğu ve oksidatif stres: Kapsamlı biyomarker analizi

Year 2025, Volume: 11 Issue: 2, 84 - 91, 30.08.2025

Zeliha Işık Bucak , Derya Kocamaz , Şule Menziletoğlu Yıldız

https://doi.org/10.30569/adiyamansaglik.1671769

Abstract

Amaç: Bu çalışma, ALS hastalarında antioksidan enzim aktiviteleri ve lipit peroksidasyon düzeylerini ölçerek oksidatif stresi değerlendirmeyi amaçlamıştır.
Gereç ve Yöntem: Bu retrospektif olgu-kontrol çalışmasına, 29 ALS tanılı hasta ve ve 24 sağlıklı birey dahil edilmiştir. Kan örneklerinde katalaz (CAT), süperoksit dismutaz (SOD), glutatyon S-transferaz (GST), glutatyon peroksidaz (GPx), glutatyon (GSH) ve lipit peroksidasyonu düzeyleri tiyobarbitürik asit reaktif maddeleri (TBARs) testi ile analiz edilmiştir.
Bulgular: ALS hastalarında CAT, SOD, GST ve GSH düzeyleri anlamlı şekilde düşük bulunurken, GPx aktivitesi ve TBARs düzeyleri artış göstermiştir. TBARs ile GST arasında saptanan negatif korelasyon, detoksifikasyon kapasitesinin bozulduğunu göstermektedir. Temel Bileşenler Analizi, özellikle GPx ve TBARs düzeylerinin etkisiyle gruplar arasında belirgin bir ayrım ortaya koymuştur.
Sonuç: Bu bulgular, ALS hastalarında belirgin bir oksidatif dengesizlik olduğunu, antioksidan savunmanın azaldığını ve lipit peroksidasyonunun arttığını göstermektedir. Bu dengesizlik, oksidatif hasarı artırarak motor nöron dejenerasyonuna ve hastalık progresyonuna katkıda bulunabilir. Bu biyobelirteçlerin izlenmesi, hastalık mekanizmalarının daha iyi anlaşılmasına ve hedefe yönelik antioksidan tedavilerin geliştirilmesine katkı sağlayabilir.

Keywords

Antioksidan sistem , Kan antioksidan profili , Lipid peroksidasyonu , Nörodejeneratif hastalıklar , Oksidatif stres

Ethical Statement

This prospective case-control study was approved by the Ethics Committee of Çukurova University (Approval No: 96, dated 14.02.2020). The study was conducted in accordance with the Helsinki declaration principles.

Supporting Institution

The author would like to thank Cukurova University for financial support (TYL2020-12851).

Thanks

The author would like to thank Cukurova University for financial support (TYL2020-12851).

Disrupted antioxidant defense and oxidative stress in amyotrophic lateral sclerosis: A comprehensive biomarker analysis

Abstract

Aim: This study aimed to assess oxidative stress in ALS patients by measuring antioxidant enzyme activities and lipid peroxidation levels.
Materials and Methods: A retrospective case-control study was conducted involving 29 ALS patients and 24 healthy controls. Blood samples were analyzed for catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione (GSH), and lipid peroxidation using the thiobarbituric acid reactive substances (TBARs) assay.
Results: ALS patients showed significantly reduced levels of CAT, SOD, GST, and GSH, whereas GPx activity and TBARs were elevated. A negative correlation between TBARs and GST indicated impaired detoxification capacity. Principal Component Analysis demonstrated clear separation between groups, primarily driven by GPx and TBARs.
Conclusion: These findings suggest a pronounced oxidative imbalance in ALS patients, marked by diminished antioxidant defenses and elevated lipid peroxidation. This imbalance may contribute to disease progression by promoting oxidative damage and motor neuron degeneration. Monitoring these biomarkers could provide valuable insights into disease mechanisms and support the development of new therapies.

Keywords

Antioxidant system , Blood antioxidant profile , Lipid peroxidation , Neurodegenerative diseases , Oxidative stress

Ethical Statement

This prospective case-control study was approved by the Ethics Committee of Çukurova University (Approval No: 96, dated 14.02.2020). The study was conducted in accordance with the Helsinki declaration principles.

Supporting Institution

The author would like to thank Cukurova University for financial support (TYL2020-12851).

Thanks

The author would like to thank Cukurova University.

References

• Mead RJ, Shan N, Reiser HJ, Marshall F, Shaw PJ. Amyotrophic lateral sclerosis: A neurodegenerative disorder poised for successful therapeutic translation. Nat Rev Drug Discov. 2023;22(3):185-212. doi:10.1038/s41573-022-00612-2.
• Hulisz D. Amyotrophic lateral sclerosis: Disease state overview. Am J Manag Care. 2018;24(15 Suppl):S320-S326.
• van Es MA, Veldink JH, Saris CG, et al. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nat Genet. 2009;41(10):1083-1087. doi:10.1038/ng.442.
• Kaymak G, Aydin H. Nörodejeneratif hastalıklarda oksidatif stresin rolü. Osmangazi J Med. 2021. doi:10.20515/otd.845217.
• Angelova PR, Esteras N, Abramov AY. Mitochondria and lipid peroxidation in the mechanism of neurodegeneration: Finding ways for prevention. Med Res Rev. 2021;41(2):770-784. doi:10.1002/med.21712.
• Dash UC, Bhol NK, Swain SK, et al. Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications. Acta Pharm Sin B. 2024. doi:10.1016/j.apsb.2024.10.004.
• Juan CA, Pérez de la Lastra JM, Plou FJ, Pérez-Lebeña E. The chemistry of reactive oxygen species (ROS) revisited: Outlining their role in biological macromolecules (DNA, lipids, and proteins) and induced pathologies. Int J Mol Sci. 2021;22(9):4642. doi:10.3390/ijms22094642.
• Singh A, Kukreti R, Saso L, Kukreti S. Oxidative stress: A key modulator in neurodegenerative diseases. Molecules. 2019;24(8):1583. doi:10.3390/molecules24081583.
• Obrador E, Salvador-Palmer R, López-Blanch R, Jihad-Jebbar A, Vallés SL, Estrela JM. The link between oxidative stress, redox status, bioenergetics and mitochondria in the pathophysiology of ALS. Int J Mol Sci. 2021;22(12):6352. doi:10.3390/ijms22126352.
• Barber SC, Shaw PJ. Oxidative stress in ALS: Key role in motor neuron injury and therapeutic target. Free Radic Biol Med. 2010;48(5):629-641. doi:10.1016/j.freeradbiomed.2009.11.018.
• Shaw PJ, Ince PG, Falkous G, Mantle D. Oxidative damage to protein in sporadic motor neuron disease spinal cord. Ann Neurol. 1995;38(4):691-695. doi:10.1002/ana.410380424.
• Ferrante RJ, Browne SE, Shinobu LA. Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis. J Neurochem. 1997;69(5):2064-2074.doi:10.1046/j.14714159.1997.69052064.x.
• Shibata N, Hirano A, Hedley-Whyte TE, Dal Canto MC, Nagai R, Uchida K, Horiuchi S, Kawaguchi M, Yamamoto T, Kobayashi M. Selective formation of certain advanced glycation end products in spinal cord astrocytes of humans and mice with superoxide dismutase-1 mutation. Acta Neuropathol. 2002;104(2):171–178. doi:10.1007/s00401-002-0547-7.
• Cunha-Oliveira T, Montezinho L, Mendes C. Oxidative stress in amyotrophic lateral sclerosis: Pathophysiology and opportunities for pharmacological intervention. Oxid Med Cell Longev. 2020; 2020:5021694. doi:10.1155/2020/5021694
• Aebi H. Catalase. In: Bergmeyer HU, ed. Methods of Enzymatic Analysis. New York, NY: Academic Press; 1974:673-684.
• McCord JM, Fridovich I. Superoxide dismutase. J Biol Chem. 1969;244(22):6049-6055. doi:10.1016/s0021-9258(18)63504-5.
• Carlberg I, Mannervik B. Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J Biol Chem. 1975;250(14):5475-5480.
• Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases: The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249(22):7130-7139.
• Beutler E. Red Cell Metabolism: A Manual of Biochemical Methods. Grune and Stratton Inc; 1984:66-71.
• Wills ED, Wilkinson AE. Release of enzymes from lysosomes by irradiation and the relation of lipid peroxide formation to enzyme release. Biochem J. 1966;99(3):657-666. doi:10.1042/bj0990657.
• Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-275.
• Park HR, Yang EJ. Oxidative stress as a therapeutic target in amyotrophic lateral sclerosis: Opportunities and limitations. Diagnostics (Basel). 2021;11(9):1546. doi:10.3390/diagnostics11091546.
• Cohen O, Kohen R, Lavon E, Abramsky O, Steiner I. Serum Cu/Zn superoxide dismutase activity is reduced in sporadic amyotrophic lateral sclerosis patients. J Neurol Sci. 1996;143(1-2):118-120. doi:10.1016/s0022-510x(96)00190-6.
• Nikolic-Kokic A, Stevic Z, Blagojevic D, Davidovic B, Jones DR, Spasic MB. Alterations in anti-oxidative defense enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients. Clin Chem Lab Med. 2006;44(5):589-593. doi:10.1515/cclm.2006.111.
• Andersen PM. Amyotrophic lateral sclerosis associated with mutations in the CuZn superoxide dismutase gene. Curr Neurol Neurosci Rep. 2006;6(1):37–46. doi:10.1007/s11910-996-0008-9.
• Szuster-Ciesielska A, Slotwinska M, Stachura A, et al. Accelerated apoptosis of blood leukocytes and oxidative stress in blood of patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(3):686-694. doi:10.1016/j.pnpbp.2007.11.012.
• Fujita K, Yamauchi M, Shibayama K, Ando M, Honda M, Nagata Y. Decreased cytochrome c oxidase activity but unchanged superoxide dismutase and glutathione peroxidase activities in the spinal cords of patients with amyotrophic lateral sclerosis. J Neurosci Res. 1996;45(3):276-281. doi:10.1002/(sici)1097-4547(19960801)45:3<276::aid-jnr9>3.0.co;2-a.
• Babu GN, Kumar A, Chandra R, et al. Oxidant-antioxidant imbalance in the erythrocytes of sporadic amyotrophic lateral sclerosis patients correlates with the progression of disease. Neurochem Int. 2008;52(6):1284-1289. doi:10.1016/j.neuint.2008.01.009.
• Apostolski S, Marinkovic Z, Nikolic A, Blagojevic D, Spasic MB, Michelson AM. Glutathione peroxidase in amyotrophic lateral sclerosis: The effects of selenium supplementation. J Environ Pathol Toxicol Oncol. 1998;17(3-4):325-329.
• Bonnefont-Rousselot D, Lacomblez L, Jaudon M, Lepage S, Salachas F, Bensimon G, Meininger V. Blood oxidative stress in amyotrophic lateral sclerosis. J Neurol Sci. 2000;178(1):57-62. doi:10.1016/s0022-510x(00)00365-8.
• Cova E, Bongioanni P, Cereda C, et al. Time course of oxidant markers and antioxidant defenses in subgroups of amyotrophic lateral sclerosis patients. Neurochem Int. 2010;56(5):687-693. doi:10.1016/j.neuint.2010.02.004.
• Moumen R, Nouvelot A, Duval D, Lechevalier B, Viader F. Plasma superoxide dismutase and glutathione peroxidase activity in sporadic amyotrophic lateral sclerosis. J Neurol Sci. 1997;151(1):35-39. doi:10.1016/s0022-510x(97)00109-3.