Antioxidant status and clinicopathological parameters in patients with Parkinson's disease

Jadranka Miletić Vukajlović; Snežana Pejić; Ana Todorović; Ana Valenta Šobot; Dunja Drakulić; Ivan Pavlović; Aleksandra Stefanović; Milica Prostran; Tihomir V Ilić; Marina Stojanov

doi:10.2298/VSP180718148M

Jadranka Miletić Vukajlović Univerzitet u BeograduInstitut za nuklearne nauke VinčaLaboratorija za fizičku hemiju
Snežana Pejić Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia
Ana Todorović Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia
Ana Valenta Šobot Department of Physical Chemistry, VINCA Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia
Dunja Drakulić Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia
Ivan Pavlović Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade, Belgrade, Republic of Serbia
Aleksandra Stefanović Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Republic of Serbia
Milica Prostran Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine – University of Belgrade, Belgrade, Republic of Serbia
Tihomir V Ilić University of Defense, Faculty of Medical Military Academy; Military Medical Academy, Clinic of Neurology, Belgrade, Republic of Serbia
Marina Stojanov Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Republic of Serbia

DOI: https://doi.org/10.2298/VSP180718148M

Ključne reči: parkinsonova bolest;, bolest, progresija;, slobodni radikali;, antioksidansi;, demografija

Sažetak

Uvod/Cilj. Ćelijska homeostaza zasniva se na konstantnoj produkciji slobodnih radikala i antioksidanasa (AO). Svako narušavanje njihove ravnoteže može dovesti ili učestvovati u patofiziološkim promenama mnogih bolesti, uključujući i Parkinsonovu bolest (PB). Kako bi se pratio status bolesti, koristi se veliki broj parametara, uključujući i prooksidativni-antioksidativni balans (PAB) i AO, koji ujedno predstavljaju i fokus ispitivanja ove studije. Stoga, cilj ove studije je bilo ispitivanje potencijalne interakcije između AO varijabli: glutation (GSH), superoksid dismutaza (SOD), katalaza (CAT) i PAB i kliničko-patoloških osobina PB bolesnika, najviše Hoehn i Yahr (H&Y) stepena bolesti. Metode. Multivarijantna analiza varijanse (MANOVA) korišćena je za analizu međusobnih razlika između kliničko-patoloških karakteristika (pola, starosti, dužine trajanja bolesti i H&Y stepena bolesti) i AO varijabli bolesnika sa PD sa onima od zdravih osoba. Studija je uključila ukupno 111 ispitanika, 91 bolesnika kojima je dijagnostifikovana idiopatska PB i 20 zdravih osoba. Rezultati. Multivarijantni efekat je bio procenjen na 0,269 (p < 0,000), što implicira da se 27,0% varijanse zavisne varijable odnosi na H&Y stepen bolesti. Univarijantni test je pokazao da postoji statistički značajna razlika (p < 0,001) kroz H&Y stepen bolesti svih AO varijabli. H&Y stepen bolesti ostao je značajan predikator i nakon uvođenja druge varijable, dužine trajanja bolesti (p < 0,001; η²= 0,249). Pokazano je da je ostala značajna razlika kroz H&Y stepen bolesti za sve varijable, tako da se jačina odnosa dve varijable kretala od 0,132 (lnGSH) do i dalje visokih vrednosti: 0,535 (lnPAB), 0,627 (lnSOD) i 0,964 (lnCAT). Zaključak. Rezultati pokazuju da je visoki nivo oksidativnog stresa u krvi obolelih od PB verovatno povezan sa stepenom bolesti. Zajedno sa smanjenjem aktivnosti SOD i nivoa GSH, aktivnost CAT se povećava u poređenju sa ovim vrednostima kod zdravih osoba. Pored toga, PAB ukazuje na povećani oksidativni stres kod obolelih od PB.

Biografija autora

Jadranka Miletić Vukajlović, Univerzitet u BeograduInstitut za nuklearne nauke VinčaLaboratorija za fizičku hemiju

Laboratorija za fizičku hemiju

istraživač saradnik

Reference

Jinsmaa Y, Florang VR, Rees JN, Mexas LM, Eckert LL, Allen EM, et al. Dopamine-derived biological reactive intermediates and protein modifications: Implications for Parkinson's dis-ease. Chem Biol Interact 2011; 192(1–2): 118–21.

Kalia LV, Lng AE. Parkinson’s disease. Lancet 2015; 386(9996): 896–912.

Blesa J, Trigo-Damas I, Quiroga-Varela A, Jackson-Lewis VR. Oxidative stress and Parkinson's disease. Front Neuroanat 2015; 9: 91.

Bolisetty S, Jaimes EA. Mitochondria and reactive oxygen spe-cies: physiology and pathophysiology. Int J Mol Sci 2013; 14(3): 6306–44.

Dröge W. Free radicals in the physiological control of cell function. Physiol Rev 2002; 82(1): 47–95.

Gandhi S, Abramov AY. Mechanism of oxidative stress in neu-rodegeneration. Oxid Med Cell Longev 2012; 2012: 428010.

Carocho M, Ferreira IC. A review on antioxidants, prooxidants and related controversy: natural and synthetic compounds, screening and analysis methodologies and future perspectives. Food Chem Toxicol 2013; 51: 15–25.

Fridovich I. Superoxide radical and superoxide dismutases. An-nu Rev Biochem 1995; 64: 97–112.

Dasuri K, Zhang L, Keller JN. Oxidative stress, neurodegenera-tion, and the balance of protein degradation and protein syn-thesis. Free Radic Biol Med 2013; 62: 170–85.

Schafer FQ, Buettner GR. Redox environment of the cell as viewed through the redox state of the glutathione disul-fide/glutathione couple. Free Radic Biol Med 2001; 30(11): 1191–212.

Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological func-tions and human disease. Int J Biochem Cell Biol 2007; 39(1): 44–84.

Masella R, Di Benedetto R, Varì R, Filesi C, Giovannini C. Nov-el mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. J Nutr Biochem 2005; 16(10): 577–86.

Sahebkar A, Mohammadi A, Atabati A, Rahiman S, Tavallaie S, Iranshahi M, et al. Curcuminoids Modulate Pro-Oxidant–Antioxidant Balance but not the Immune Response to Heat Shock Protein 27 and Oxidized LDL in Obese Individuals. Phytother Res 2013; 27(12): 1883–88.

Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychia-try 1992; 55(3): 181–4.

Beutler E. Catalase. In: Beutler E, editor. Red cell metabolism: a manual of biochemical methods. 3rd ed. Orlando, FL: Grune and Stratton; 1984: p. 105–6.

Miletić J, Drakulić D, Pejić S, Petković M, Ilić TV, Miljković M, et al. Prooxidant–antioxidant balance, advanced oxidation pro-tein products and lipid peroxidation in Serbian patients with Parkinson's disease. Int J Neurosci 2018; 128(7): 600–7.

Hayyan M, Hashim MA, AlNashef IM. Superoxide ion: genera-tion and chemical implications. Chem Rev 2016; 116(5): 3029–85.

de la Torre MR, Casado A, López-Fernández ME, Carrascosa D, Casado MC, Venarucci D, et al. Human aging brain disorders: role of antioxidant enzymes. Neurochem Res 1996; 21(8): 885–8.

Bostantjopoulou S, Kyriazis G, Katsarou Z, Kiosseoglou G, Kazis A, Mentenopoulos G. Superoxide dismutase activity in early and advanced Parkinson’s disease. Funct Neurol 1997; 12(2): 63–8.

Ihara Y, Chuda M, Kuroda S, Hayabara T. Hydroxyl radical and superoxide dismutase in blood of patients with Parkinson’s isease:relationship to clinical data. J Neurol Sci 1999; 170(2): 75–6.

Abraham S, Soundararajan CC, Vivekanandhan S, Behari M. Erythrocyte antioxidant enzymes in Parkinson’s disease. Indi-an J Med Res 2005; 121(2): 111–5.

Younes-Mhenni S, Frih-Ayed M, Kerkeni A, Bost M, Chazot G. Peripheral blood markers of oxidative stress in Parkinson’s disease. Eur Neurol 2007; 58(2): 78–83.

Kalra J, Rajput AH, Mantha SV, Prasad K. Serum antioxidant enzyme activity in Parkinson’s disease. Mol Cell Biochem 1992; 110(2): 165–8.

Kocaturk PA, Akbostanci MC, Tan F, Kavas GO. Superoxide dismutase activity and zinc and copper concentrations in Par-kinson’s disease. Pathophysiology 2000; 7(1): 63–7.

Serra JA, Dominguez RO, De Lustig ES, Guareschi EM, Famulari AL, Bartolomé EL, et al. Parkinson’s disease is associated with oxidative stress: comparison of peripheral antioxidant profiles in living Parkinson’s, Alzheimer’s and vascular dementia pa-tients. J Neural Transm (Vienna) 2001; 108(10): 1135–48.

Barthwal MK, Srivastava N, Shukla R, Nag D, Seth PK, Srirnal RC, et al. Polymorphonuclear leukocyte nitrite content and antioxidant enzymes in Parkinson's disease patients. Acta Neurol Scand 1999; 100(5): 300–4.

Sudha K, Rao AV, Rao S, Rao A. Free radical toxicity and an-tioxidants in Parkinson’s disease. Neurol India 2003; 51(1): 60–2.

Hu N, Ren J. Reactive Oxygen Species Regulate Myocardial Mitochondria through Post-Translational Modification. ROS 2016; 2(4): 264–71.

Ahmad A, Shameem M, Husain Q. Altered oxidant-antioxidant levels in the disease prognosis of chronic obstructive pulmo-nary disease. Int J Tuberc Lung Dis 2013; 17(8): 1104–9.

Aziz MA, Majeed GH, Diab KS, Al-Tamimi RJ. The associa-tion of oxidant–antioxidant status in patients with chronic re-nal failure. Ren Fail 2016; 38(1): 20–6.

Liu Z, Zhou T, Ziegler AC, Dimitrion P, Zuo L. Oxidative stress in neurodegenerative diseases: from molecular mechanisms to clinical applications. Oxid Med Cell Longev 2017; 2017: 2525967.

Polidori MC, Stahl W, Eichler O, Niestroj I, Sies H. Profiles of antioxidants in human plasma. Free Radic Biol Med 2001; 30(5): 456–62.

Durham HD, Roy J, Dong L, Figlewicz DA. Aggregation of mu-tant Cu/Zn superoxide dismutase proteins in a culture model of ALS. J Neuropathol Exp Neurol 1997; 56(5): 523–30.

Kilinç A, Yalçin AS, Yalçin D, Taga Y, Emerk K. Increased erythrocyte susceptibility to lipid peroxidation in human Park-inson's disease. Neurosci Lett 1988: 87(3): 307–10.

Makino N, Mochizuki Y, Bannai S, Sugita Y. Kinetic studies on the removal of extracellular hydrogen peroxide by cultured fi-broblasts. J Biol Chem 1994; 269(2): 1020–5.

Flohé L, Loschen G, Gunzler WA, Eichele E. Glutathione perox-idase, V. The kinetic mechanism. Hoppe Seylers Z Physiol Chem 1972; 353(6): 987–99.

Todorović A, Pejić S, Stojiljković V, Gavrilović L, Popović N, Pavlović I, et al. Antioxidative enzymes in irradiated rat brain-indicators of different regional radiosensitivity. Childs Nerv Syst 2015; 31(12): 2249–56.

Saleh L, Plieth C. Total low-molecular-weight antioxidants as a summary parameter, quantified in biological samples by a chemiluminescence inhibition assay. Nat Protoc 2010; 5(10): 1627–34.

Alamdari DH, Paletas K, Pegiou T, Sarigianni M, Befani C, Kolia-kos G. A novel assay for the evaluation of the prooxidant-antioxidant balance, before and after antioxidant vitamin ad-ministration in type II diabetes patients. Clin Biochem 2007; 40(3–4): 248–54.

Zeevalk GD, Razmpour R, Bernard LP. Glutathione and Parkin-son's disease: is this the elephant in the room? Biomed Phar-macother 2008; 62(4): 236–49.

Mischley LK, Standish LJ, Weiss NS, Padowski JM, Kavanagh TJ, White CC, et al. Glutathione as a biomarker in Parkinson’s disease: Associations with aging and disease severity. Oxid Med Cell Longev 2016; 2016: 9409363.

Meister A, Anderson ME. Glutathione. Annu Rev Biochem 1983; 52: 711–60.

Aquilano K, Baldelli S, Ciriolo MR. Glutathione: new roles in redox signaling for an old antioxidant. Front Pharmacol 2014; 5: 196.

Lu SC. Regulation of glutathione synthesis. Mol Aspects Med 2009; 30(1–2): 42–59.

Malone PE, Hernandez MR. 4-Hydroxynonenal, a Product of Oxidative Stress, Leads to an Antioxidant Response in Optic Nerve Head Astrocytes. Exp Eye Res 2007; 84(3): 444–54.

Ballatori N, Krance SM, Marchan R, Hammond CL. Plasma membrane glutathione transporters and their roles in cell phys-iology and pathophysiology. Mol Aspects Med 2009; 30(1–2): 13–28.

Mischley LK, Lau RC, Shankland EG, Wilbur TK, Padowski JM. Phase IIb Study of Intranasal Glutathione in Parkinson’s Dis-ease. J Parkinsons Dis 2017; 7(2): 289–99.

Otto M, Magerus T, Langland J. The Use of Intravenous Gluta-thione for Symptom Management of Parkinson’s Disease: A Case Report. Altern Ther Health Med 2017; pii: AT494.

Sechi G, Deledda MG, Bua G, Satta WM, Deiana GA, Pes GM, et al. Reduced intravenous glutathione in the treatment of early Parkinson's disease. Prog Neuropsychopharmacol Biol Psychiatry 1996; 20(7): 1159–70.