Correlation of Oxidative Stress Biomarkers and Hematological Parameters in Blood Cancer Patients from Sardinia, Italy
Background: Over the last few decades, there has been a dramatic increase in hematological malignancies (HMs) in the population of Sardinia. It is accepted that oxidative stress biomarkers have been demonstrated to be prognostically important in various neoplastic diseases. The aim of this study is to evaluate serum vitamin E, total antioxidant capacity (TAC), Malondialdehyde (MDA) and reactive oxygen species (ROS) levels in 80 Sardinian patients with different HMs [acute myeloid leukemia (AML)(n=20), myelodysplastic syndromes (MDS) (n=20), Hodgkin lymphoma (HL) (n=20) and non-Hodgkin lymphoma (NHL) (n=20)] on the day of their diagnosis.
Materials and Methods: Samples from all participants were obtained after an overnight fast (at least 10 hours). This study was approved and conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. Patients and controls provided written, informed consent before entering the study. All study participants’ medical history and their medication were documented upon enrolling.
Results: Lower levels of TAC and Vitamin E were observed in most of the studied groups compared to healthy controls (0.41-0.49 mmol/L vs. 0.56 mmol/L) (19.55-28.55 μmol/L vs. 34.51 μmol/L). Moreover, higher average MDA levels were observed in HL and NHL patients compared to healthy controls (16.6 ng/ml-17.8 ng/ml vs. 7.4 ng/ml). Additionally, the ROS values of all studied groups were found elevated. Serum TAC showed significant negative correlations with MDA values (R= -0.51; P<0.001). Statistical significance was observed in all hematological parameters, producing either positive or negative correlation with at least one OS biomarker.
Conclusion: The present data suggest that Sardinian patients with HL and NHL on the day of their diagnosis presented the highest OS in comparison to AML and healthy subjects. Moreover, MDS patients presented high OS status. Likewise, our results also indicated that changes in their hematological indices are eminent of their oxidative and antioxidative status.
2. Broccia G, Gabbas A, Longinotti M. Newly diagnosed cases of hematologic malignancies in Sardinia in the early 2000: an estimation of their number, age and geographic distribution on the basis of a previous epidemiologic survey. Haematologica. 2005;90(3):429-30.
3. Cao A, Galanello R, Furbetta M, et al. Thalassaemia types and their incidence in Sardinia. J Med Genet. 1978;15(6):443-7.
4. Lenzerini L, Meera Khan P, Filippi G, et al. Characterization of glucose-6-phosphate dehydrogenase variants. I. Occurrence of a G6PD Seattle-like variant in Sardinia and its interaction with the G6PD Mediterranean variant. Am J Hum Genet. 1969;21(2):142-53.
5. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010; 5(6):463-6.
6. Marrocco I, Altieri F, Peluso I. Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans. Oxid Med Cell Longev. 2017;2017:6501046.
7. Pitocco D, Tesauro M, Alessandro R, et al. Oxidative stress in diabetes: implications for vascular and other complications. Int J Mol Sci. 2013; 14(11):21525-21550.
8. Aguilar R, Marrocco T, Skorokhod OA, et al. Blood oxidative stress markers and Plasmodium falciparum malaria in non-immune African children. Br J Haematol. 2014;164(3):438-50.
9. Percário S, Moreira DR, Gomes BA, et al. Oxidative stress in malaria. Int J Mol Sci. 2012; 13(12):16346-72.
10. Pantaleo A, Ferru E, Pau MC, et al. Band 3 Erythrocyte Membrane Protein Acts as Redox Stress Sensor Leading to Its Phosphorylation by p (72) Syk. Oxid Med Cell Longev. 2016;2016:6051093.
11. Costa VM, Carvalho F, Bastos ML, et al. Contribution of catecholamine reactive intermediates and oxidative stress to the pathologic features of heart diseases. Curr Med Chem. 2011; 18(15):2272-314.
12. Liu Z, Zhou T, Ziegler AC, et al. Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications. Oxid Med Cell Longev. 2017;2017:2525967.
13. Uttara B, Singh AV, Zamboni P, et al. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 2009;7(1):65-74.
14. Tsamesidis I, Fozza C, Vagdatli E, et al. Total antioxidant capacity in Mediterranean beta-thalassemic patients. Adv Clin Exp Med. 2017; 26(5):789-793.
15. Vanella A, Campisi A, Castorina C, et al. Antioxidant enzymatic systems and oxidative stress in erythrocytes with G6PD deficiency: effect of deferoxamine. Pharmacol Res. 1991;24(1):25-31.
16. Goncalves A, Cortesao E, Oliveiros B, et al. Oxidative stress and mitochondrial dysfunction play a role in myelodysplastic syndrome development, diagnosis, and prognosis: a pilot study. Free Radic Res. 2015; 49(9):1081-94.
17. Camargo Cde Q, Borges Dda S, de Oliveira PF, et al. Individuals with hematological malignancies before undergoing chemotherapy present oxidative stress parameters and acute phase proteins correlated with nutritional status. Nutr Cancer. 2015;67(3):463-71.
18. Masutani H. Oxidative stress response and signaling in hematological malignancies and HIV infection. Int J Hematol. 2000;71(1):25-32.
19. Bowen D, Wang L, Frew M, et al. Antioxidant enzyme expression in myelodysplastic and acute myeloid leukemia bone marrow: further evidence of a pathogenetic role for oxidative stress? Haematologica. 2003;88(9):1070-2.
20. Bur H, Haapasaari KM, Turpeenniemi-Hujanen T, et al. Oxidative stress markers and mitochondrial antioxidant enzyme expression are increased in aggressive Hodgkin lymphomas. Histopathology. 2014;65(3):319-27.
21. Wang SS, Davis S, Cerhan JR, et al. Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma. Carcinogenesis. 2006;27(9):1828-34.
22. Battisti V, Maders LD, Bagatini MD, et al. Measurement of oxidative stress and antioxidant status in acute lymphoblastic leukemia patients. Clin Biochem. 2008;41(7-8):511-8.
23.Pimková K, Chrastinová L, Suttnar J, et al. Plasma levels of aminothiols, nitrite, nitrate, and malondialdehyde in myelodysplastic syndromes in the context of clinical outcomes and as a consequence of iron overload. Oxid Med Cell Longev. 2014; 2014: 416028.
24. Fracchiolla NS CA, Orofino N, Novembrino C, et al. Oxidative Stress as Marker of Sepsis in Onco Hematological Patients: A Pilot Study. J Blood Disord Transfus. 2015; 6(5):311.
25. Kuhn V, Diederich L, Keller TCS 4th, et al. Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia. Antioxid Redox Signal. 2017; 26(13):718-742.
26. Cosentino-Gomes D, Rocco-Machado N, Meyer-Fernandes JR. Cell signaling through protein kinase C oxidation and activation. Int J Mol Sci. 2012; 13(9): 10697–10721.
27. Reuter S, Gupta SC, Chaturvedi MM, et al. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010; 49(11):1603-16.
28. Gupta RK, Patel AK, Shah N, et al. Oxidative stress and antioxidants in disease and cancer: a review. Asian Pac J Cancer Prev. 2014; 15(11):4405-9.
29. Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem. 2015; 97: 55-74.
30. Dröge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002; 82(1):47-95.
31. Blokhina O, Virolainen E, Fagerstedt KV. Antioxidants, oxidative damage and oxygen deprivation stress: a review. Ann Bot. 2003; 91 Spec No: 179-94.
32. Apostolidou C, Adamopoulos K, Lymperaki E, et al. Cardiovascular risk and benefits from antioxidant dietary intervention with red wine in asymptomatic hypercholesterolemics. Clin Nutr ESPEN. 2015; 10(6):e224-e233.
33. Fucile C, Marini V, Zuccoli ML, et al. HPLC determination of malondialdehyde as biomarker for oxidative stress: application in patients with alcohol dependence. Clin Lab. 2013; 59(7-8):837-41.
34. Oparka M, Walczak J, Malinska D, et al. Quantifying ROS levels using CM-H2DCFDA and HyPer. Methods. 2016;109:3-11.
35. Frijhoff J, Winyard PG, Zarkovic N, et al. Clinical Relevance of Biomarkers of Oxidative Stress. Antioxid Redox Signal. 2015; 23(14):1144-70.
36. Lee JD, Cai Q, Shu XO, et al. The Role of Biomarkers of Oxidative Stress in Breast Cancer Risk and Prognosis: A Systematic Review of the Epidemiologic Literature. J Womens Health (Larchmt). 2017; 26(5):467-482.
37. Omoti CE, Benedict N, ES I, et al. Total Antioxidant Capacity (TAC) in Patients with Haematological Malignancies in Niger Delta-region of Nigeria. Am J Cancer Sci. 2013; 2: 101-107.
38. Swart Ld, Reiniers C, Bagguley T, et al. Plasma Iron Levels Predict Survival in Patients with Lower-Risk Myelodysplastic Syndromes. Haematologica. 2018; 103(1):69-79.
39. Pilo F, Angelucchi E. A storm in the niche: Iron, oxidative stress and haemopoiesis. Blood Rev. 2018; 32(1):29-35.
40. Udensi UK, Tchounwou PB. Dual effect of oxidative stress on leukemia cancer induction and treatment. J Exp Clin Cancer Res. 2014; 33: 106.
41. Fiaschi T, Chiarugi P. Oxidative stress, tumor microenvironment, and metabolic reprogramming: a diabolic liaison. Int J Cell Biol. 2012; 2012:762825.