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Indian Journal of Clinical Biochemistry logoLink to Indian Journal of Clinical Biochemistry
. 2008 Dec 20;23(4):328–333. doi: 10.1007/s12291-008-0072-9

Oxidative stress and antioxidant status in patients with chronic myeloid leukemia

Rizwan Ahmad 2, Anil K Tripathi 1,2, Payal Tripathi 1,2, Ranjana Singh 2, Sushma Singh 2, Raj K Singh 2,
PMCID: PMC3453137  PMID: 23105780

Abstract

Chronic myeloid leukemia is a myeloproliferative disorder with a unique rearrangement, the Philadelphia chromosome. Oxidative stress, a pervasive condition of an increased number of reactive oxygen species, is now recognized to be prominent feature of various diseases and their progression. Thus antioxidants, which control the oxidative stress state, represent a major line of defense regulating overall true state of health. The relationship between antioxidants status and levels of well-known markers of oxidative stress that are measured as lipid peroxides and oxidized proteins reflect better health indices and postures. The aim of this study was to evaluate the role of oxidative stress in pathophysiology of Chronic myeloid leukemia by measuring the circulating plasma lipid peroxide levels in terms of malonyldialdehyde, total lipid hydroperoxide and oxidized proteins as protein carbonyl whereas antioxidant status were estimated in terms of reduced glutathione and total thiol in plasma of Chronic myeloid leukemia patients. The present study included 47 Chronic myeloid leukemia patients and 20 age-and sex-matched healthy subjects. Out of 47 Chronic myeloid leukemia patients, 31 were in chronic phase (CML-CP) and 16 in accelerated phase (CML-AP). The median age of Chronic myeloid leukemia patients was 33 years and that of controls was 32 years. Oxidative stress and antioxidant status in plasma were evaluated by spectrophotometric procedures. There was a significant increase (p<0.05) in plasma malonyldialdehyde, total lipid hydroperoxide and protein carbonyl levels in Chronic myeloid leukemia patients as compared to healthy subjects. Our results also showed that plasma malonyldialdehyde and protein carbonyl levels were markedly elevated (p<0.05) in both chronic phase (CML-CP) and accelerated phase (CML-AP) as compared to healthy volunteers. Antioxidant status was found to be significantly decreased (p<0.05) in Chronic myeloid leukemia patients and its phases as compared to healthy participants. It could be concluded that oxidative stress may be associated with the pathophysiology of Chronic myeloid leukemia.

Key Words: Chronic myeloid leukemia, Oxidative stress, Antioxidants, Malonyldialdehyde, Total lipid hydroperoxide, Protein carbonyl

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References

  • 1.Nowell P.C., Hungerford D.A. A minute chromosome in human chronic granulocytic leukemia [abstract] Science. 1960;132:1497. [Google Scholar]
  • 2.Kurzrock R., Kantarjian H.M., Drucker B.J., Talpaz M. Philadelphia chromosome-positive leukemias: From basic mechanisms to molecular therapeutics. Ann Intern Med. 2003;138:819–830. doi: 10.7326/0003-4819-138-10-200305200-00010. [DOI] [PubMed] [Google Scholar]
  • 3.Frei B. Reactive oxygen species and antioxidant vitamins: mechanisms of action. Am J Med. 1994;97:S5–S13. doi: 10.1016/0002-9343(94)90292-5. [DOI] [PubMed] [Google Scholar]
  • 4.Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 3rd Edition. Oxford University Press, 1999.
  • 5.Irshad M., Chaudhuri P.S. Oxidant-antioxidant system: Role and significance in human body. Ind J Exp Biol. 2002;40:1233–1239. [PubMed] [Google Scholar]
  • 6.Dalle-Donne I., Rossi R., Colombo R., Giustarini D., Milazani A. Biomarkers of oxidative stress in human disease. Clin Chem. 2006;52:601–623. doi: 10.1373/clinchem.2005.061408. [DOI] [PubMed] [Google Scholar]
  • 7.Ray G., Batra S., Shukla N.K., Deo S., Raina V., Ashok S., Husain S.A. Lipid peroxidation, free radical production and antioxidant status in breast cancer. Breast Cancer Research and Treatment. 2000;59:163–170. doi: 10.1023/A:1006357330486. [DOI] [PubMed] [Google Scholar]
  • 8.Suzuki Y.J., Forman H.J., Sevanian A. Oxidants as stimulators of signal transduction. Free Rad Biol Med. 1997;22:269–285. doi: 10.1016/S0891-5849(96)00275-4. [DOI] [PubMed] [Google Scholar]
  • 9.Galli F., Piroddi M., Annetti C., Aisa C., Floridi E., Floridi A. Oxidative stress and reactive oxygen species. Contrib Nephrol. 2005;149:240–260. doi: 10.1159/000085686. [DOI] [PubMed] [Google Scholar]
  • 10.Singh V., Ghalaut P.S., Kharb S., Singh G.P. Plasma concentrations of lipid peroxidation products in children with acute leukemia. Ind J Med Sci. 2001;55:215–217. [PubMed] [Google Scholar]
  • 11.Sie H. oxidative stress: from basic research to clinical application. Am J Med. 1991;9:31–38. doi: 10.1016/0002-9343(91)90281-2. [DOI] [PubMed] [Google Scholar]
  • 12.Manoharan S., Kolanjiappan K., Suresh K., Panjamutrhy K. Lipid peroxidation and antioxidant status in patients with oral squamous cell carcinoma. Ind J Med Res. 2005;122:529–534. [PubMed] [Google Scholar]
  • 13.Czeczot H., Scibior D., Skrzycki M., Podsiad M. Glutathione and GSH-dependent enzymes in patients with liver cirrhosis and hepatocellular carcinoma. Acta Biochemia Polonica. 2006;53:237–241. [PubMed] [Google Scholar]
  • 14.Navarro J., Obrador E., Carretero J., Petschen I., Avino J., Perez P., Estrela J.M. Change in glutathione status and the antioxidant system in blood and in cancer cells associate with tumor growth in vivo. Free Radic Biol Med. 1999;26:410–418. doi: 10.1016/S0891-5849(98)00213-5. [DOI] [PubMed] [Google Scholar]
  • 15.Uzun H., Konukoglu D., Gelisgen R., Zengin K., Taskin M. plasma protein carbonyl and thiol stress before and after laproscopic gastric banding in morbidly obese patients. Obesity Surgery. 2007;17:1367–1373. doi: 10.1007/s11695-007-9242-8. [DOI] [PubMed] [Google Scholar]
  • 16.Draper H.H., Hadley M. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol. 1990;186:421–431. doi: 10.1016/0076-6879(90)86135-I. [DOI] [PubMed] [Google Scholar]
  • 17.Wolf S.P. Ferrous ion oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxide. Methods Enzymol. 1994;233:182–189. doi: 10.1016/S0076-6879(94)33021-2. [DOI] [Google Scholar]
  • 18.Levine R.L., Garland D., Oliver C.N., Amici A., Climent I., Lenz A.G., Ahn B.W., Shaltiel S., Stadtman E.R. Determination of carbonyl content of oxidatively modified proteins. Methods Enzymol. 1990;186:464–478. doi: 10.1016/0076-6879(90)86141-H. [DOI] [PubMed] [Google Scholar]
  • 19.Lowry O.H., Rosebrough N.J., Farr A.L., Randall R.J. Protein measurement with the Folin phenol reagents. J Biol Chem. 1951;193:265–275. [PubMed] [Google Scholar]
  • 20.Beutler E., Duran O., Kelly M.B. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963;61:882–888. [PubMed] [Google Scholar]
  • 21.Hu M.L. Measurement of protein thiol group and glutathione in plasma. Methods Enzymol. 1994;233:381–385. doi: 10.1016/s0076-6879(94)33044-1. [DOI] [PubMed] [Google Scholar]
  • 22.Cerutti P.A. Pro-oxidant status and tumor promotion. Science. 1985;227:375–381. doi: 10.1126/science.2981433. [DOI] [PubMed] [Google Scholar]
  • 23.Dalle-Donne I., Aldini G., Carini M., Colombo R., Rossi R., Milazani A. Protein carbonylation, cellular dysfunction, and disease progression. J Cell Mol Med. 2006;10(2):389–406. doi: 10.1111/j.1582-4934.2006.tb00407.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Cerutti P.A. Oxy-radicals and cancer. Lancet. 1994;344:862–863. doi: 10.1016/S0140-6736(94)92832-0. [DOI] [PubMed] [Google Scholar]
  • 25.Dormandy T.I. An approach to free radicals. Lancet. 1983;1:1010–1014. doi: 10.1016/S0140-6736(83)90989-3. [DOI] [PubMed] [Google Scholar]
  • 26.Ghalaut V.S., Ghalaut P.S., Singh S. Lipid peroxidation in leukemia. J Asso Phys Ind. 1999;47:403–405. [PubMed] [Google Scholar]
  • 27.Abd-El-Rahman M.A.H., Soliman S.F., Tolba K.A., El-Kabbany Z.A., Makhlouf M.S. Plasma concentrations of lipid peroxidation products in children with acute lymphoblastic leukemia. Clin Chem. 1992;38:594–595. [PubMed] [Google Scholar]
  • 28.Manju V., Kalaivani Sailaja J., Nalini N. Circulating lipid peroxidation and antioxidant status in cervical cancer patients: a case-control study. Clin Biochem. 2002;35:621–625. doi: 10.1016/S0009-9120(02)00376-4. [DOI] [PubMed] [Google Scholar]
  • 29.Geetha A., Karthiga S., Surendran G., Jayalakshmi G. Biochemical studies on the level of lipid hydroperoxide and antioxidants in different types of obstructive jaundice. J Lab Med. 2001;2:20–27. [Google Scholar]
  • 30.Pignatelli B., Li C.Q., Boffetta P., Chen Q., Ahrens W., Nyberg F., et al. Nitrated and oxidized protein in smokers and lung cancer patients. Cancer Research. 2001;61(2):778–784. [PubMed] [Google Scholar]
  • 31.Yilmaz I.A., Akçay T., Cakatay U., Telci A., Ataus S., Yalçin V. R. Relation between bladder and protein oxidation. Int Urol Nephrol 20. 2003;35(3):345–350. doi: 10.1023/B:UROL.0000022920.93994.ba. [DOI] [PubMed] [Google Scholar]
  • 32.Morabito F., Cristani M., Saija A., Stelitano C., Callea V., Tomaino A., et al. Lipid peroxidation and protein oxidation in patients affected by Hodgkin’s lymphoma. Mediators Inflam. 2004;13(5–6):381–383. doi: 10.1155/S0962935104000584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Popadiuk S., Korzon M., Renke J., Wozniak M. Carbonyl group content on the basis of protein peroxidation analysis with total antioxidant status in blood of children with cancers. Wiad Lek. 1998;51:107–112. [PubMed] [Google Scholar]
  • 34.Wu G., Fang Y.Z., Yang S., Lupton J.R., Turner N.D. Glutathione Metabolism and Its Implications for Health. J Nutr. 2004;134:489–492. doi: 10.1093/jn/134.3.489. [DOI] [PubMed] [Google Scholar]
  • 35.Oberley L.W., Oberley T.D. Role of antioxidant enzymes in cell immortalization and transformation. Mol Cell Biochem. 1988;84:147–153. doi: 10.1007/BF00421049. [DOI] [PubMed] [Google Scholar]
  • 36.Sun Y. Free radicals, antioxidant enzymes and carcinogenesis. Free Radic Biol Med. 1990;8:583–599. doi: 10.1016/0891-5849(90)90156-D. [DOI] [PubMed] [Google Scholar]
  • 37.Bakan N., Taysi S., Yilmaz O., Bakan E., Kuskay S., Uzun N. Glutathione peroxidase, glutathione reductase, Cu-Zn superoxide dismautase activities, glutathione, nitric oxide, and malondialdehyde concentrations in serum of patients with chronic myeloid leukemia. Clin Chim Acta. 2003;338:143–149. doi: 10.1016/j.cccn.2003.08.013. [DOI] [PubMed] [Google Scholar]
  • 38.Kharb S., Singh V., Ghalaut P.S., Sharma A., Singh G.P. Glutathione levels in health and sickness. Ind J Med Sci. 2000;54:52–54. [PubMed] [Google Scholar]
  • 39.Giacomo C.D., Acquaviva R., Lanteri R., Licata F., Licata A., Vanella A. Nonproteic antioxidant status in plasma of subjects with colon cancer. Exp Biol Med. 2003;228:525–528. doi: 10.1177/15353702-0322805-17. [DOI] [PubMed] [Google Scholar]
  • 40.Andersson A., Lindgren A., Arnadottir M., Prytz H., Hultberg B. Thiols as a measure of plasma redox status in healthy subjects and in patients with renal or liver failure. Clin Chem. 1999;45:1084–1087. [PubMed] [Google Scholar]
  • 41.Weijl N.I., Leton F.J., Osanto S. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treat Rev. 1997;23:209–240. doi: 10.1016/S0305-7372(97)90012-8. [DOI] [PubMed] [Google Scholar]
  • 42.Sangeetha P., Das U.N., Koratkar R., Suryaprabha P. Increase in free radical generation and lipid peroxidation following chemotherapy in patients with cancer. Free Radic Biol Med. 1990;8:15–19. doi: 10.1016/0891-5849(90)90139-A. [DOI] [PubMed] [Google Scholar]
  • 43.Lauterburg B.H., Nguyen T., Hartmann B., Junker E., Kupfer A., Cerny T. Depletion of total cysteine, glutathione, and homocysteine in plasma by ifosfamide/mesna therapy. Cancer Chemother Pharmacol. 1994;35:132–136. doi: 10.1007/BF00686635. [DOI] [PubMed] [Google Scholar]
  • 44.Wu W.S. The signaling mechanism of ROS in tumor progression. Cancer Metastasis Rev. 2006;25:695–705. doi: 10.1007/s10555-006-9037-8. [DOI] [PubMed] [Google Scholar]
  • 45.Sattler M., Verma S., Shrikhande G., Byrne C.H., Pride Y.B., Winkler T., et al. The BCR/ABL tryrosine kinase induces production of reactive oxygen species in hematopoietic cells. J Biol Chem. 2000;275:24273–24278. doi: 10.1074/jbc.M002094200. [DOI] [PubMed] [Google Scholar]
  • 46.Koptyra M., Falinski R., Nowicki M., Stoklosa T., Majsterek I., Nieborowska-Skorska M., Blasiak J., Skorski T. BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance. Blood. 2006;108(1):319–327. doi: 10.1182/blood-2005-07-2815. [DOI] [PMC free article] [PubMed] [Google Scholar]

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