The relationship between melatonin level, oxidative stress, fatigue and sleep disorders in multiple sclerosis patients

Year 2024, , 168 - 174, 08.03.2024

Yıldız Dağcı , Nuray Bilge , Mustafa Ceylan , Halil İbrahim Özkan

https://doi.org/10.38053/acmj.1395276

Cited By: 1

Abstract

Aims: Our study aimed to investigate the relationship between oxidative stress and melatonin levels, sleep disturbances and fatigue in persons with MS (pwMS).
Methods: The study included 50 pwMS and 30 healthy controls. Levels of serum melatonin, glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured in both groups. Persons with MS (pwMS) were evaluated using the extended disability status scale (EDDS) while Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale, insomnia severity index, fatigue severity scale and Beck depression scale were used for both groups.
Results: Persons with MS (pwMS) exhibited significantly higher sleep disturbances (p<0,001), PSQI score (p<0,001), sleep latency (p=0,014), insomnia severity (p=0,001), fatigue (0,001) and fatigue severity (p<0,001), and Beck depression scale scores (p<0,001) and SOD levels (p<0,001) compared to the control group, while exhibiting significantly lower levels of melatonin(p=0,004). In pwMS, patients who experienced difficulty sleeping had significantly lower melatonin levels compared to those who did not (p=0,049). In pwMS, the melatonin level showed a negative correlation with age (r=-0,341; p=0,015) and EDSS (r=-0,386; p=0,006). Persons with MS (pwMS) with fatigue had significantly higher EDSS (p=0,003), PUQI (p=0,001), Epworth sleepiness score (p=0,028) and insomnia scores (p=0,002), compared to those who didn’t.
Conclusion: Our results showed that the melatonin levels were lower, presence of fatigue, and fatigue severity were higher in pwMS with sleep disorders than in those without sleep disorders. The frequent occurrence of fatigue(indirectly) and sleep disturbances in pwMS can be attributed to low melatonin levels.

Keywords

Multiple sclerosis, melatonin, sleep disturbances, oxidative stress, fatigue

Ethical Statement

The study was initiated with the approval of the Atatürk University Medical Faculty Clinical Researches Ethics Committee (02/3 / 29.03.2018).

References

• Comabella M, Khoury SJ. Immunopathogenesis of multiple sclerosis. Clin Immunol. 2012;142(1):2-8.
• Kamm CP, Uitdehaag BM, Polman CH. Multiple sclerosis: current knowledge and future outlook. Eur Neurol. 2014;72(3-4):132-141.
• Golan D, Staun-Ram E, Glass-Marmor L, et al. The influence of vitamin D supplementation on melatonin status in patients with multiple sclerosis. Brain Behav Immun. 2013;32:180-185.
• Gilgun-Sherki Y, Melamed E, Offen D. The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol. 2004;251(3):261-268.
• Korkmaz A, Reiter RJ, Topal T, Manchester LC, Oter S, Tan DX. Melatonin: an established antioxidant worthy of use in clinical trials. Mol Med. 2009;15(1):43-50.
• Cote I, Trojan DA, Kaminska M, et al. Impact of sleep disorder treatment on fatigue in multiple sclerosis. Mult Scler. 2013;19(4):480-489.
• Hagan RM, Oakley NR. Melatonin comes of age? Trends Pharmacol Sci. 1995;16(3):81-83.
• Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurol. 1983;33(11):1444-1452.
• Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale: application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46(10):1121-1123.
• Agargun M. Pittsburgh uyku kalitesi indeksinin gecerligi ve guvenirligi. Turk Psikiyatri Derg. 1996;7:107-115.
• Izci B, Ardic S, Firat H, Sahin A, Altinors M, Karacan I. Reliability and validity studies of the Turkish version of the Epworth sleepiness scale. Sleep Breath. 2008;12(2):161-168.
• Boysan M, Güleç M, Besiroglu L, Kalafat T. Uykusuzluk şiddeti indeksi’nin Türk örneklemindeki psikometrik özellikleri. Anadolu Psikiyatri Derg. 2010;11(3):248-252.
• Hisli N. Beck Depresyon envanterinin gecerliligi uzerine bit calisma (a study on the validity of Beck depression inventory.). Psikol Derg. 1988;6:118-122.
• Anisimov VN, Popovich IG, Zabezhinski MA, Anisimov SV, Vesnushkin GM, Vinogradova IA. Melatonin as antioxidant, geroprotector and anticarcinogen. Biochim Biophys Acta. 2006; 1757(5-6):573-589.
• Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95(2):351-358.
• Khanzode SD, Dakhale GN, Khanzode SS, Saoji A, Palasodkar R. Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors. Redox Rep. 2003;8(6):365-370.
• Smolders J, Peelen E, Thewissen M, et al. The relevance of vitamin D receptor gene polymorphisms for vitamin D research in multiple sclerosis. Autoimmun Rev. 2009;8(7):621-626.
• Sakkas GK, Giannaki CD, Karatzaferi C, Manconi M. Sleep abnormalities in multiple sclerosis. Curr Treat Options Neurol. 2019;21(1):4.
• Haider L, Fischer MT, Frischer JM, et al. Oxidative damage in multiple sclerosis lesions. Brain. 2011;134(7):1914-1924.
• Ferretti G, Bacchetti T. Peroxidation of lipoproteins in multiple sclerosis. J Neurol Sci. 2011;311(1-2):92-97.
• Adamczyk-Sowa M, Sowa P, Pierzchala K, Polaniak R, Labuz-Roszak B. Antioxidative enzymes activity and malondialdehyde concentration during mitoxantrone therapy in multiple sclerosis patients. J Physiol Pharmacol. 2012;63(6):683-690.
• Tasset I, Agüera E, Sánchez-López F, et al. Peripheral oxidative stress in relapsing-remitting multiple sclerosis. Clin Biochem. 2012;45(6):440-444.
• Hedström AK, Åkerstedt T, Hillert J, Olsson T, Alfredsson L. Shift work at young age is associated with increased risk for multiple sclerosis. Ann Neurol. 2011;70(5):733-741.
• Adamczyk-Sowa M, Pierzchala K, Sowa P, Polaniak R, Kukla M, Hartel M. Influence of melatonin supplementation on serum antioxidative properties and impact of the quality of life in multiple sclerosis patients. J Physiol Pharmacol. 2014;65(4):543-550.
• McCord JM. Human disease, free radicals, and the oxidant/antioxidant balance. Clin Biochem. 1993;26(5):351-357.
• Kostoglou-Athanassiou I. Therapeutic applications of melatonin. Ther Adv Endocrinol Metab. 2013;4(1):13-24.
• Wurtman RJ, Zhdanova I. Improvement of sleep quality by melatonin. Lancet. 1995;346(8988):1491.
• Ebers GC. Environmental factors and multiple sclerosis. Lancet Neurol. 2008;7(3):268-277.
• Emre U, Ergün U, Yıldız H, Coşkun Ö, İnan L. Multipl sklerozda depresyon. Düşünen Adam. 2003;16(1):53-56.