Protein carbonyl products, malondialdehyde, glutathione and vitamins C/E of breast cancer patients subjected to chemotherapy

ABSTRACT

Introduction: Various endogenous and exogenous processes contribute to the production of oxidative stress, of which anticancer drugs may be one. This study aimed at evaluating the effect of breast cancer chemotherapy on oxidative stress.

Material and Methods: Oxidative markers and antioxidant defense molecules were monitored in 59 women undergoing a year of treatment for breast cancer.

Results: During the treatment, the levels of vitamin C and glutathione decreased, while both malondialdehyde and protein carbonyl products increased. Vitamin E levels were affected to a smaller extent. The patients were grouped by principal component analysis using their oxidative stress profiles according to the time of the chemotherapy and 95.9% of the total variance was explained by the first three principal components.

Conclusion: The oxidative stress profile of the study population was modified extensively during one year of exposure to antineoplastic drugs.

RESUMO

Introdução: Vários processos endógenos e exógenos contribuem para a produção de estresse oxidativo, dos quais os fármacos antineoplásicos podem ser um deles. Este estudo teve como objetivo avaliar o efeito da quimioterapia do câncer de mama sobre o estresse oxidativo.

Material e Métodos: Marcadores oxidativos e moléculas de defesa antioxidante foram monitorados em 59 mulheres submetidas a um ano de tratamento para câncer de mama.

Resultados: Durante o tratamento, os níveis de vitamina C e glutationa diminuíram, enquanto o malondialdeído e os produtos proteicos carbonílicos aumentaram. Os níveis de vitamina E foram afetados em menor grau. As pacientes foram agrupadas por análise de componentes principais usando seus perfis de estresse oxidativo de acordo com o tempo da quimioterapia e 95,9% da variância total foi explicada pelos três primeiros componentes principais.

Conclusão: O perfil de estresse oxidativo da população estudada foi amplamente modificado, durante um ano de exposição aos antineoplásicos.

Keywords:

Oxidative stress - Biomarkers - Breast diseases

Descritores:

Estresse oxidativo - Biomarcadores - Doenças da mama

Publikationsverlauf

Eingereicht: 01. Oktober 2021

Angenommen: 03. Dezember 2021

Artikel online veröffentlicht:
13. Mai 2022

• REFERENCES

• 1 National Cancer Institute of Jose Alencar Gomes da Silva (INCA). Estimate 2020: cancer incidence in Brazil [Internet]. Rio de Janeiro (RJ): INCA; 2019. ;[access in ANO Mês dia]. Available from: https://www.inca.gov.br/sites/ufu.sti.inca.local/files/media/document/estimativa-2020-incidencia-de-cancer-no-brasil.pdf
• 2 Ferreira LLG, Andricopulo AD. Cancer estimates in Brazil reveal progress for the most lethal malignancies. Curr Top Med Chem 2020; 20 (22) 1962-1966
• 3 University Hospital Southampton (UHS), NHS Foundation Trust. Breast chemotherapy protocols [Internet]. Hampshire: UHS/NHS;; 2020. ;[access in 2020 Jun 09]. Available from: https://www.uhs.nhs.uk/HealthProfessionals/Chemotherapy-protocols/Breast-chemotherapy-protocols.aspx
• 4 Waks AG, Winer EP. Breast cancer treatment: a review. JAMA 2019; Jan; 321 (03) 288-300
• 5 Chen Y, Jungsuwadee P, Vore M, Butterfield DA, St Clair DK. Collateral damage in cancer chemotherapy: oxidative stress in nontargeted tissues. Mol Interv 2007; Jun; 7 (03) 147-156
• 6 Mahboob M, Rahman MF, Rekhadevi PV, Sailaja N, Balasubramanyam A, Prabhakar PV. et al. Monitoring of oxidative stress in nurses occupationally exposed to antineoplastic drugs. Toxicol Int 2012; Jan/Apr; 19 (01) 20-24
• 7 Gonçalves IL, Rockenbach L, Göethel G, Saüer E, Kagami LP, Neves GM. et al. New pharmacological findings linked to biphenyl DHPMs, kinesin Eg5 ligands: anticancer and antioxidant effects. Future Med Chem 2020; Jun; 12 (12) 1137-1154
• 8 Songbo M, Lang H, Xinyong C, Bin X, Ping Z, Liang S. Oxidative stress injury in doxorubicin- induced cardiotoxicity. Toxicol Lett 2019; Jun; 307: 41-48
• 9 Meshkini A, Yazdanparast R. Involvement of oxidative stress in taxol-induced apoptosis in chronic myelogenous leukemia K562 cells. Exp Toxicol Pathol 2012; May; 64 (04) 357-365
• 10 Oboh G, Ogunruku OO. Cyclophosphamide-induced oxidative stress in brain: protective effect of hot short pepper (Capsicum frutescens L. var. abbreviatum). Exp Toxicol Pathol 2010; May; 62 (03) 227-233
• 11 Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J 2012; Jan; 5 (01) 9-19
• 12 Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med 2011; sep; 51 (05) 1000-1013
• 13 Fu J, Wu Z, Liu J, Wu T. Vitamin C: a stem cell promoter in cancer metastasis and immunotherapy. Biomed Pharmacother 2020; Nov; 131: 110588
• 14 Cong G, Yan R, Sachdev U. Low serum vitamin C correlates with an increased risk of peripheral arterial disease in current smokers: Results from NHANES 2003-2004. Int J Cardiol Hypertens 2020; Sep; 6: 100037
• 15 Alghamdi F, Al-Seeni MN, Ghoneim MA. Potential synergistic antioxidant effect of thymoquinone and vitamin E on cisplatin-induced acute nephropathy in rats. Clin Nutr Exp 2020; 32: 29-37
• 16 Gaucher C, Boudier A, Bonetti J, Clarot I, Leroy P, Parent M. Glutathione: antioxidant properties dedicated to nanotechnologies. Antioxidants (Basel) 2018; Apr; 7 (05) 62
• 17 Bansal A, Simon MC. Glutathione metabolism in cancer progression and treatment resistance. J Cell Biol 2018; Jul; 217 (07) 2291-2298
• 18 Traverso N, Ricciarelli R, Nitti M, Marengo B, Furfaro AL, Pronzato MA. et al. Role of glutathione in cancer progression and chemoresistance. Oxid Med Cell Longev 2013; 2013: 972913
• 19 Chevion M, Berenshtein E, Stadtman ER. Human studies related to protein oxidation: protein carbonyl content as a marker of damage. Free Rad Res 2000; Nov; 33 (Suppl 1): S99-S108
• 20 Weber D, Davies MJ, Grune T. Determination of protein carbonyls in plasma, cell extracts, tissue homogenates, isolated proteins: focus on sample preparation and derivatization conditions. Redox Biol 2015; Aug; 5: 367-380
• 21 Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014; 2014: 360438
• 22 Il'yasova D, Mixon G, Wang F, Marcom PK, Marks J, Spasojevich I. et al. Markers of oxidative status in a clinical model of oxidative assault: a pilot study in human blood following doxorubicin administration. Biomarkers 2009; 14 (05) 321-325
• 23 Panis C, Herrera AC, Victorino VJ, Campos FC, Freitas LF, Rossi T. et al. Oxidative stress and hematological profiles of advanced breast cancer patients subjected to paclitaxel or doxorubicin chemotherapy. Breast Cancer Res Treat 2012; May; 133 (01) 89-97
• 24 Chala E, Manes C, Iliades H, Skaragkas G, Mouratidou D, Kapantais E. Insulin resistance, growth factors and cytokine levels in overweight women with breast cancer before and after chemotherapy. Hormones (Athens) 2006; Apr/Jun; 5 (02) 137-146
• 25 Kasapović J, Pejić S, Stojiljković V, Todorović A, Radoŝević-Jelić L, Saiĉić ZS. et al. Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages after chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide. Clin Biochem 2010; Nov; 43 (16-17): 1287-1293
• 26 Silva FB, Romero WG, Carvalho ALRA, Souza GAA, Claudio ERG, Abreu GR. Effects of treatment with chemotherapy and/or tamoxifen on the biomarkers of cardiac injury and oxidative stress in women with breast cancer. Medicine 2017; Nov; 96 (47) e8723
• 27 Karatepe M. Simultaneous determination of ascorbic acid and free malondialdehyde in human serum by HPLC-UV. LCGC North America 2004; 22: 104-106
• 28 Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG. et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 1990; 186: 464-478
• 29 Hansen LG, Warwick WJ. A fluorometric micromethod for serum vitamins A and E. Tech Bull Regist Med Technol 1969; Mar; 39 (03) 70-73
• 30 Akerboom T, Sies H. Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Methods Enzymol 1981; 77: 373-382
• 31 Tualeka AR, Martiana T, Ahsan A, Russeng SS, Meidikayanti W. Association between malondialdehyde and glutathione (l-gamma-glutamyl-cysteinyl-glycine/ GSH) levels on workers exposed to benzene in Indonesia. Open Access Maced J Med Sci 2019; Apr; 7 (07) 1198-1202
• 32 Lenton KJ, Therriault H, Cantin AM, Fülöp T, Payette H, Wagner JR. Direct correlation of glutathione and ascorbate and their dependence on age and season in human lymphocytes. Am J Clin Nutr 2000; May; 71 (05) 1194-1200
• 33 Karki K, Pande D, Negi R, Khanna RS, Khanna HD. An assessment of oxidative damage and non-enzymatic antioxidants status alteration in relation to disease progression in breast diseases. Med Sci (Basel) 2016; Dec; 4 (04) 17
• 34 Feng JF, Lu L, Dai CM, Wang D, Yang YH, Yang YW. et al. Analysis of the diagnostic efficiency of serum oxidative stress parameters in patients with breast cancer at various clinical stages. Clin Biochem 2016; Jun; 49 (09) 692-698
• 35 Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J. Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/ radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany. In Vivo 2011; Nov/Dec; 25 (06) 983-990
• 36 Cappetta D, Angelis A, Sapio L, Prezioso L, Illiano M, Quaini F. et al. Oxidative stress and cellular response to doxorubicin: a common factor in the complex milieu of anthracycline cardiotoxicity. Oxid Med Cell Longev 2017; 2017: 1521020