Cortisol levels and serum antioxidant status following chemotherapy


Chemotherapy results in increased free radical formation and depletion of tissue antioxidants. Moreover, patients receiving chemotherapy are under emotional stress, which is also accompanied by low antioxidant levels. In the present study, we measured cortisol, the main stress hormone, and total antioxidant capacity (TAC) in serum of 51 cancer patients during chemotherapy. Antioxidant activity was estimated by measuring the influence of serum in oxidation of ABTS (2,2'-azino-bis (3-ethylbenz-thiazoline-6-sulfonic acid to ABTS+ by methmyoglobin (Antioxidant kit of Cayman). Serum cortisol was measured using an ELISA colorimetric assay. Serum TAC was significantly decreased (75% decrease compared to normal levels, p = 0.001) in all patients during chemotherapy, while blood cortisol concentration was increased by 10%, (p = 0.044). Lower antioxidant levels and higher cortisol concentration were detected in patients receiving chemotherapeutic drugs daily, compared to the ones receiving chemotherapy once a week. A difference between sexes was observed with male patients presenting lower antioxidant status and higher cortisol levels than females. A significant and persistent decrease in antioxidant capacity accompanied by increased cortisol concentration was observed in all patients during chemotherapy. This fact, which is probably generated by biological and emotional stress, increases the probability of harmful side effects and organism weakening and needs to be considered during patients’ treatment.

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Limberaki, E. , Eleftheriou, P. , Gasparis, G. , Karalekos, E. , Kostoglou, V. and Petrou, C. (2011) Cortisol levels and serum antioxidant status following chemotherapy. Health, 3, 512-517. doi: 10.4236/health.2011.38085.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Skrzydlewska, E., Stankiewicz, A., Sulkowska, M., Sul- kowski, S. and Kasacka, I. (2001) Aantioxidant status and lipid peroxidation in colorectal cancer. Journal of Toxicology and Environmental Health, 64, 213-222. doi:10.1080/15287390152543690
[2] Shacter, E., Williams, J.A., Hinson, R.M., Senturker, S. and Lee, Y.J. (2000) Oxidative stress interferes with cancer chemotherapy: Inhibition of lymphoma cell apoptosis and phagocytosis. Blood, 96, 307-313.
[3] Lee, Y.J. and Shacter, E. (1999) Oxidative stress inhibits apoptosis in human lymphoma cells. Journal of Biolo- gical Chemistry, 274, 19792-19798. doi:10.1074/jbc.274.28.19792
[4] Weijl, N.I., Leton, F.J. and Osanto, S. (1997) Free radi- cals and antioxidants in chemotherapy-induced toxicity. Cancer Treatment Reviews, 23, 209-240. doi:10.1016/S0305-7372(97)90012-8
[5] Durken, M., Agbenu, J., Finckh, B., Hübner, C., Pichl- meier, U., Zeller, W., et al. (1995) Deteriorating free radicaltrapping capacity and antioxidant status in plasma during bone marrow transplantation. Bone Marrow Transplant, 15, 757-762.
[6] Lauterburg, B.H., Nguyen, T., Hartmann, B., Junker, E., Kupfer, A. and Cerny, T. (1994) Depletion of total cysteine, glutathione, and homocysteine in plasma by ifosfamide/mesna therapy. Cancer Chemotherapy and Pharmacology, 35,132-136. doi:10.1007/BF00686635
[7] Crohns, M., Liippo, K., Erhola, M., Kankaanranta, H., Moilanen, E., Alho, H., et al. (2009) Concurrent decline of several antioxidants and markers of oxidative stress during combination chemotherapy for small cell lung cancer. Clinical Biochemistry, 42, 1236-1245. doi:10.1016/j.clinbiochem.2009.05.003
[8] Ladner, C., Ehninger, G., Gey, K.F. and Clemens, M.R. (1989) Effect of etoposide (VP16–213) on lipid peroxi- dation and antioxidant status in a highdose radiochemo- therapy regimen. Cancer Chemotherapy and Pharma- cology, 25, 210-212. doi:10.1007/BF00689585
[9] Faure, H., Coudray, C., Mousseau, M., Ducros, V., Douki, T., Bianchini, F., et al. (1996) 5-Hydroxymethyluracil excretion, plasma TBARS and plasma antioxidant vita- mins in adriamycin-treated patients. Free Radical Biol- ogy and Medicine, 20, 979-983. doi:10.1016/0891-5849(95)02187-6
[10] Bhuvarahamurthy, V., Balasubramanian, N. and Govin- dasamy, S. (1996) Effect of radiotherapy and chemo- therapy on circulating antioxidant system of human uter- ine cervical carcinoma. Molecular and Cellular Bio- chemistry, 158, 17-23.
[11] Gadjeva, V., Dimov, A. and Georgieva, N. (2008) Influ- ence of therapy on the antioxidant status in patients with melanoma. Journal of Clinical Pharmacy and Therapeu- tics, 33, 179-185. doi:10.1111/j.1365-2710.2008.00909.x
[12] Papageorgiou, M., Stiakaki, E., Dimitriou, H., Malliaraki, N., Notas, G., Castanas, E., et al. (2005) Cancer chemotherapy reduces plasma total antioxidant capacity in children with malignancies. Leukemia Research, 29, 11- 16. doi:10.1016/j.leukres.2004.04.017
[13] Ten Kate, M., van der Wal, J.B., Sluiter, W., Hofland, L.J., Jeekel, J., Sonneveld, P., et al. (2008) The role of superoxide anions in the development of distant tumour recurrence. British Journal of Cancer, 98, 580-586.
[14] Burstein, H.J., Gelber, S., Guadagnoli, E. and Weeks, J.C. (1999) Use of alternative medicine by women with early-stage breast cancer. New England Journal of Medicine, 340, 1733-1739. doi:10.1056/NEJM199906033402206
[15] Van de Creek, L., Rogers, E. and Lester, J. (1999) Use of alternative therapies among breast cancer outpatients compared with the general population. Alternative Thera- pies in Health and Medicine, 5, 71-76.
[16] D’Andrea, G.M. (2005) Use of antioxidants during chemotherapy and radiotherapy should be avoided. A Cancer Journal for Clinicians, 55, 319-321.
[17] Pace, A., Savarese, A., Picardo, M., Maresca, V., Pacetti, U., Del Monte, G., et al. (2003) Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. Journal of Clinical Oncology, 21, 927-931. doi:10.1200/JCO.2003.05.139
[18] Iarussi, D., Auricchio, U., Agretto, A., Murano, A., Giuliano, M., Casale, F., et al. (1994) Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: Control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Molecular Aspects of Medicine, 15, 207-212.
[19] Weijl, N.I., Elsendoorn, T.J., Lentjes, E.G., Hopman, G.D., Wipkink-Bakker, A., Zwinderman, A.H., et al. (2004) Supplementation with antioxidant micronutrients and chemotherapy-induced toxicity in cancer patients treated with cisplatin-based chemotherapy: A randomised, double-blind, placebo-controlled study. European Journal of Cancer, 40, 1713-1723.
[20] Guaiquil, V.H., Vera, J.C. and Golde, DW. (2001) Mecha- nism of vitamin C inhibition of cell death induced by oxidative stress in glutathione-depleted HL-60 cells. Jour- nal of Biological Chemistry, 276, 40955-40961. doi:10.1074/jbc.M106878200
[21] Lesperance, M.L., Olivotto, I.A., Forde, N., Zhao, Y., Speers, C., Foster, H., et al. (2002) Mega-dose vitamins and minerals in the treatment of non-metastatic breast cancer: An historical cohort study. Breast Cancer Research and Treatment, 76, 137-143. doi:10.1023/A:1020552501345
[22] Bjelakovic, G., Nikolova, D., Simonetti, R.G. and Gluud, C. (2004) Antioxidant supplements for prevention of gastrointestinal cancers: A systematic review and meta- analysis. Lancet, 364, 1219-1228.
[23] Greggi Antunes, L.M., Darin, J.D. and Bianchi, M.D. (2000) Protective effects of vitamin C against cisplatin-induced nephrotoxicity and lipid peroxidation in adult rats: A dose-dependent study. Pharmacological Research, 41, 405-411. doi:10.1006/phrs.1999.0600
[24] Chinery, R., Brockman, J.A., Peeler, M.O., Shyr, Y., Beauchamp, R.D. and Coffey, R.J. (1997) Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer: A p53-independent induction of p21 WAF1/CIP1 via C/EBPbeta. Nature Medicine, 3, 1233- 1241.
[25] Daubeuf, S., Balin, D., Leroy, P. and Visvikis, A. (2003) Different mechanisms for gamma-glutamyltranspepti- dase-dependent resistance to carboplatin and cisplatin. Biochemical Pharmacology, 66, 595-604.
[26] Agelaki, S., Tsatsanis, C., Gravanis, A. and Margioris, A.N. (2002) Corticotropin-releasing hormone augments proinflammatory cytokine production from macrophages in vitro and in lipopolysaccharide-induced endotoxin shock in. Infection and Immunity, 70, 6068-6074.
[27] Lovallo, W.R., Farag, N.H., Vincent, A.S., Thomas, T.L. and Wilson, M.F. (2006) Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women. Pharmacology Biochemistry and Behaviour, 83, 441-447. doi:10.1016/j.pbb.2006.03.005
[28] Ruzic, B., Tomaskovic, I., Trnski, D., Kraus, O., Beka- vac-Beslin, M. and Vrkic, N. (2005) Systemic stress responses in patients undergoing surgery for benign pro- static hyperplasia. BJU International, 95, 77-80.
[29] Lutgendorf, SK., Weinrib, A.Z., Penedo, F., Russell, D., DeGeest, K. and Costanzo, E. (2008) Interleukin-6, cortisol, and depressive symptoms in ovarian cancer patients. Journal of Clinical Oncology, 26, 4820-4827. doi:10.1200/JCO.2007.14.1978
[30] Young, A.H. (2004) Cortisol in mood disorders. Stress, 7, 205-208.
[31] Wang, L., Muxin, G., Nishida, H., Shirakawa, C., Sato, S. and Konishi, T. (2007) Psychological stress-induced oxidative stress as a model of sub-healthy condition and the effect of TCM. Evidence Based Complementary and Alternative Medicine, 4, 195-202.
[32] Marusin, A.V., Salyukov, V.B. and Yu Bragina, E. (2002) Antioxidant activity of blood plasma in individuals with neoplasms. Bulletin of Experimental Biology and Medicine, 133, 481-483.
[33] Thakor, A.S. and Giussani, D.A. (2005) Antioxidants enhance the adrenocortical response to stress in the fetus. Endocrine Abstracts, 196th Meeting of the Society for Endocrinology, London, UK, 7-9 November 2005, 10 OC22
[34] Erel, O.A. (2004) Novel automated method to measure total antioxidant response against potent free radical reactions. Clinical Biochemistry, 37, 112-119.
[35] Perry, L.A. and Gossman, A.B. (1997) The role of the laboratory in the diagnosis of Cushing’s syndrome. Annals of Clinical Biochemistry, 34, 345-359.
[36] Press, W.H., Teukolsky, S.A., Vetterling, W.T. and Flannery B.P. (1992) Numerical Recipes in C: The art of scientific computing. Cambridge University Press, Cambridge.
[37] Almawi, W.Y. and Melemedjian, O.K. (2002) Negative regulation of nuclear factor-kappab activation and function by glucocorticoids. Journal of Molecular Endocrinology, 28, 69-78. doi:10.1677/jme.0.0280069
[38] Marumo, T., Schini-Kerth, V.B., Brandes, R.P. and Busse, R. (1998) Glucocorticoids inhibit superoxide anion production and p22 phox mRNA expression in human aortic smooth muscle cells. Hypertension, 32, 1083-1088.
[39] Peji?, S., Todorovi?, A., Stojiljkovi?, V., Cvetkovi?, D., Luci?, N., Radojici?, R.M., et al. (2008) Superoxide dismutase and lipid hydroperoxides in blood and endometrial tissue of patients with benign, hyperplastic and malignant endometrium. Annals of the Brazilian Academy of Science, 80, 515-522.
[40] Swaab, D.F., Raadsheer, F.C., Endert, E., Hofman Kamphorst, M.W. and Ravid, R. (2006) Increased cortisol levels in Aging and Alzheimer’s disease in postmortem cerebrospinal fluid. Journal of Neuroendocrinology, 6, 681-687. doi:10.1111/j.1365-2826.1994.tb00635.x
[41] Morrow, G.R., Hickok, J.T., Andrews, P.L. and Stern, R.M. (2002) Reduction in serum cortisol after platinum based chemotherapy for cancer: A role for the HPA axis in treatment-related nausea? Psychophysiology, 39, 491- 495. doi:10.1111/1469-8986.3940491
[42] Paris, J.J., Franco, C., Sodano, R., Freidenberg, B., Gordis, E., Anderson, D.A., et al. (2010) Sex differences in salivary cortisol in response to acute stressors among healthy participants, in recreational or pathological gamblers, and in those with posttraumatic stress disorder. Hormones and Behaviour, 57, 35-45. doi:10.1016/j.yhbeh.2009.06.003
[43] McCann, J. (2000) Gender differences in cancer that don’t make sense—Or do they? Journal of the National Cancer Institute, 92, 1560-1562. doi:10.1093/jnci/92.19.1560

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