Investigation of the Oxidative Process by Measuring Total Antioxidant Capacity and Total Oxidant Capacity in Patients with Gaucher Disease

Abstract

Background

Gaucher disease is caused by mutations in the GBA1 gene, which encodes the β-glucocerebrosidase enzyme. The deficiency of this enzyme result in glucosylceramide and glucosylsphingosine accumulation, within lysosomes and resulted triggering inflammation and accumulating substrates affect multiple organ systems, causing progressive cellular damage. Evidence has shown that the accumulation of glucosylceramide in macrophages is associated with inflammatory processes, reactive oxygen species production and an imbalance between the pro-oxidants and the antioxidant reserve, resulting in oxidative stress and inflammation.

Aims

The aim of this study was to compare the oxidative stress status between patients with Gaucher disease and healthy controls.

Study design

Case-control study

Materials and Methods

This study included 10 patients with Gaucher disease aged between 2–40 years, and 30 healthy controls. Total antioxidant capacity and total oxidant capacity parameters between these groups were compared.

Results

Although the total antioxidant capacity value of the case group was higher, it was not significant. The total oxidant capacity and oxidative stress index values were significantly higher in the patient group (p<0.05).

Conclusion

Our study showed that oxidative stress increased in patients with Gaucher disease. The results of our study may guide the application of antioxidant treatment in Gaucher disease patients as a supportive treatment.

Zusammenfassung

Hintergrund

Die Gaucher-Krankheit wird durch Mutationen im GBA1-gen verursacht, das für das enzym β-Glukozerebrosidase kodiert. Der Mangel an diesem Enzym führt zur Akkumulation von Glucosylceramid und Glucosylsphingosin in den Lysosomen und löst Entzündungen aus. Die Ansammlung von Substraten wirkt sich auf mehrere Organsysteme aus und verursacht fortschreitende Zellschäden. Es gibt Hinweise darauf, dass die Akkumulation von Glucosylceramid in Makrophagen mit entzündlichen Prozessen, der Produktion reaktiver Sauerstoffspezies und einem Ungleichgewicht zwischen den Prooxidantien und der Antioxidantienreserve verbunden ist, was zu oxidativem Stress und Entzündungen führt.

Ziele

Ziel dieser Studie war es, den oxidativen Stressstatus zwischen Patienten mit Gaucher-Krankheit und gesunden Kontrollpersonen zu vergleichen.

Studiendesign:

Fall-Kontroll-Studie.

Materialien und Methoden:

An dieser Studie nahmen 10 Patienten mit Gaucher-Krankheit im Alter zwischen 2 und 40 Jahren sowie 30 gesunde Kontrollpersonen teil. Die Parameter der Gesamtantioxidationskapazität und der Gesamtoxidationskapazität zwischen diesen Gruppen wurden verglichen.

Ergebnisse

Obwohl der Gesamtwert der antioxidativen Kapazität in der Fallgruppe höher war, war er nicht signifikant. Die Gesamtoxidationskapazität und die Indexwerte für oxidativen Stress waren in der Patientengruppe signifikant höher (p<0,05).

Schlussfolgerung

Unsere Studie zeigte, dass oxidativer Stress bei Patienten mit Gaucher-Krankheit zunahm. Die Ergebnisse unserer Studie könnten als unterstützende Maßnahme für die Anwendung einer antioxidativen Behandlung bei Patienten mit Gaucher-Krankheit dienen.

Keywords

Gaucher disease - oxidativen stress - total oxidant capacity - total antioxidant capacity

Schlüsselwörter

Gaucher krankheit - Oxidativen stress - Gesamt antioxidant kapazität - Gesamt oxidant kapazität

Publication History

Article published online:
05 May 2025

• References

• 1 Castillon G, Chang SC, Moride Y. Global Incidence and Prevalence of Gaucher Disease: A Targeted Literature Review. J Clin Med 2022; 12: 85
• 2 Stirnemann J, Belmatoug N, Camou F. et al. Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. Int J Mol Sci 2017; 18: 441
• 3 Mello AS, Garcia CS, Machado FS. et al. Oxidative stress parameters of Gaucher disease type I patients. Molecular Genetics and Metabolism Reports 2015; 4: 1-5
• 4 Valko M, Leibfritz D, Moncol J. et al. Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell Biology 2007; 39: 44-84
• 5 Mello AS, Garcia CS, Souza Machado FS. et al. Oxidative stress parameters of Gaucher disease type I patients. Molecular Genetics and Metabolism Reports 2015; 4: 1-5
• 6 Mozafari H, Khatami S, Kiani A. et al. Oxidative Stress Parameters, Trace Elements, and Lipid Profile in Iranian Patients with Gaucher Disease. Biol Trace Elem Res 2020; 193: 130-7
• 7 Schlesier K, Harwat M, Böhm V. et al. Assessment of antioxidant activity by using different in vitro methods. Free Radic Res 2002; 36: 177-87
• 8 Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38: 1103-11
• 9 Cam V, Olgac A, Kilic M. et al. Oxidative Stress in Intoxıcation Type Inborn Errors of Metabolism using Thiol-Disulfide Ratio. J Coll Physicians Surg Pak 2021; 30: 663-667
• 10 Mc Guire PJ, Parikh A, Diaz GA. Profiling of oxidative stress in patients with inborn errors of metabolism. Mol Genet Metab 2009; 98: 173-80
• 11 Vardar Acar N, Dursun A, Aygün D. et al. An investigation of different intracellular parameters for Inborn Errors of Metabolism: Cellular stress, antioxidant response and autophagy. Free Radic Biol Med 2022; 179: 190-9
• 12 Pierzynowska K, Gaffke L, Cyske Z. et al. Oxidative Stress in Mucopolysaccharidoses: Pharmacological Implications. Molecules. 2021; 26: 5616
• 13 Donida B, Marchetti DP, Biancini GB. et al. Oxidative stress and inflammation in mucopolysaccharidosis type IVA patients treated with enzyme replacement therapy. Biochim Biophys Acta – Mol Basis Dis 2015; 1: 1852 :1012–9
• 14 Pascua-Maestro R, Diez-Hermano S, Lillo C. et al. Protecting cells by protecting their vulnerable lysosomes: identification of a new mechanism for preserving lysosomal functional integrity upon oxidative stress. PLoS Genet 2017; 13: 1-33
• 15 Mello AS, da Silva Garcia C, de Souza Machado F. et al Oxidative stress parameters of Gaucher disease type I patients. Mol Genet Metab Rep 2015; 22 4 1-5
• 16 Cleeter MWJ, Chau KY, Gluck C. et al. Glucocerebrosidase inhibition causes mitochondrial dysfunction and free radical damage. Neurochemistry International 2013; 62: 1-7
• 17 Deganuto M, Pittis MG, Pines A. et al. Altered intracellular redox status in Gaucher disease fibroblasts and impairment of adaptive response against oxidative stress. J Cell Physiol 2007; 212: 223-5
• 18 de la Mata M., Cotán D., Oropesa-Ávila M.. et al. Coenzyme Q 10 partially restores pathological alterations in a macrophage model of Gaucher disease. Orphanet J Rare Dis 2017; 12: 23
• 19 Biancini GB, Vanzin CS, Rodrigues DB, Deon M, Ribas GS. et al. Globotriaosylceramide is correlated with oxidative stress and inflammation in Fabry patients treated with enzyme replacement therapy. Biochim Biophys Acta 2012; 1822: 226-232
• 20 Kartha RV, Terluk MR, Brown R. et al. Patients with Gaucher disease display systemic oxidative stress dependent on therapy status. Mol Genet Metab Rep 2020; 25: 100667
• 21 Deganuto M, Pittis MG, Pines A. et al. Altered intracellular redox status in Gaucher disease fibroblasts and impairment of adaptive response against oxidative stress. J Cell Physiol 2007; 212: 223-35
• 22 Roversi FM, Galdieri LC, Grego BH. et al. Blood oxidative stress markers in Gaucher disease patients. Clin Chim Acta 2006; 364: 316-20
• 23 Mozafari H, Khatami S, Kiani A. et al. Oxidative Stress Parameters, Trace Elements, and Lipid Profile in Iranian Patients with Gaucher Disease. Biol Trace Elem Res 2020; 193: 130-137
• 24 Zahran AM, Elsayh KI, El-Deek SE. et al. Oxidative stress, trace elements, and circulating microparticles in patients with Gaucher disease before and after enzyme replacement therapy. Clin Appl Thromb Hemost 2015; 21: 58-65
• 25 Kartha R.V, Joers J, Terluk MR. et al. Neurochemical abnormalities in patients with type 1 Gaucher disease on standard of care therapy. J Inherit Metab Dis 43 2020; 564-573
• 26 Seo CH, Kim JB. Therapeutic Potential of Resveratrol in Type I Gaucher Disease. Phytother Res 2015; 29: 835-9