Skip to main content
Log in

Prophylactic action of melatonin against cyclophosphamide-induced oxidative stress in mice

  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

The present study investigated the prophylactic influence of melatonin against cyclophosphamide-induced oxidative stress in mouse tissues. Lipid peroxidation, reduced glutathione (GSH), glutathione disulphide (GSSG), glutathione peroxidase (GSH-Px) and serum phosphatase levels were analyzed in brain, spleen liver, lungs, kidney and testes. Fifteen days oral administration with melatonin (0.1 mg/kg bw per day) before treatment checked the augmentation of the level of lipid peroxidation, blood GSSG and acid phosphatase caused by an acute treatment with a radiomimetic drug, cyclophosphamide (75 mg/kg bw). Cyclophosphamide-induced depletion in the level of GSH, GSH-Px and alkaline phosphatase was made up statistically significant by chronic melatonin administration given orally. The results indicate the antioxidative properties of melatonin resulting into its prophylactic property against the cyclophosphamide-induced biochemical alterations. The finding support the idea that melatonin is a potent free-radical scavenger and antioxidant.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Allegra M, Reiter RJ, Tan DX, Gentile G, Tesoriere L, Livrea MA. The chemistry of melatonin's interaction with reactive species. J Pineal Res. 2003;34:1–10.

    Google Scholar 

  • Anderstam B, Vaca C, Ringdahl MH. Lipid peroxide level in a murine adenocarcinoma exposed to hyperthermia: the role of glutathione depletion. Radiat Res. 1992;132:296–300.

    Google Scholar 

  • Anisimov VN, Popovich IG, Zabezhinski MA. Melatonin and colon carcinogenesis: I. Inhibitory effects of melatonin on development of intestinal tumors induced by 1, 2-dimethylhydrazine in rats. Carcinogenesis. 1997;18:1549–53.

    Google Scholar 

  • Blask DE. Melatonin in oncology. In: Yu, HS and Reiter RJ, eds. Melatonin, biosynthesis, physiological effects, and clinical applications. Boca Raton, FL: CRC Press; 1993:447–75.

    Google Scholar 

  • Bueg JA, Aust SD. Methods in enzymology, Vol. 52. New York: Academic Press; 1978:302–14.

    Google Scholar 

  • Cerutti P. Peroxidant states and tumor production. Science. 1985;227:337–81.

    Google Scholar 

  • Comporti M. Glutathione depleting agents and lipid peroxidation. Chem Phys Lipids. 1987;45:143–69.

    Google Scholar 

  • De Salvia R, Fiore M, Aglitti T, Festa F, Ricordy R, Cozzi R. Inhibitory action of melatonin on H2O2-and cyclophosphamide-induced DNA damage. Mutagenesis. 1999;14:107–12.

    Google Scholar 

  • Ellman GL, Archs. Tissue sulfhydril groups. Biochem Biophys. 1959;82:70–7.

    Google Scholar 

  • Gul M, Kutay FZ, Temocin S, Hanninen O. Cellular and clinical implication of glutathione. Ind J Exp Biol. 2000;38:625–34.

    Google Scholar 

  • Halliwell B. Free radicals, antioxidants and human disease: curiosity, cause or consequence? Lancet. 1994;344:721–4.

    Google Scholar 

  • Hatoroft WS. Atheroma begins at birth. In: Kummerow FA, eds. Metabolism of lipids as related to atherosclerosis. IL, USA: Springfield; 1965:18–25.

    Google Scholar 

  • Hochstein P and Utley H. Hydrogen peroxide detoxification by glutathione peroxidase and catalase in rat liver homogenate. Mol Pharmacol. 1968;4:574–9.

    Google Scholar 

  • Kale RK, Sitaswad SL. Radiation induced lipid peroxidation in liposomes. Radiat Phys Chem. 1990;36:361–4.

    Google Scholar 

  • Kaya H, Oral B, Ozguner F, et al. The effect of melatonin application on lipid peroxidation during cyclophosphamide therapy in female rats. Zentralbl Gynakol. 1999; 121:499–502.

    Google Scholar 

  • Leyko W, Bartosz G. Membranes effect of ionizing radiation and hyperthermia. Int J Radiat Biol. 1986;49:743–70.

    Google Scholar 

  • Lopez-Gonzalez MA, Guerrero JM, Torronteras R, Osuna C, Delgado F. Ototoxicity caused by aminoglycosidase is ameliorated by melatonin without interfering with the antibiotic capacity of the drugs. J Pineal Res. 2000;28:26–33.

    Google Scholar 

  • Lopez-Gonzalez MA, Guerrero JM, Torronteras R, Osuna C, Delgado F. Ototoxicity caused by cisplatine is ameliorated by melatonin and other antioxidants. J Pineal Res. 2000;28:73–80.

    Google Scholar 

  • Manda K, Bhatia AL. Melatonin-induced reduction in age-related accumulation of oxidative damage in mice. Biogerontology. 2003a; 4(3):133–9.

    Google Scholar 

  • Manda K, Bhatia AL. Melatonin's anti-aging role: a study on LPO in mice tissues. Ind J Gerontol. 2003b;16:211–17.

    Google Scholar 

  • Meister A, Andersen ME. Glutathione. Ann Rev Biochem. 1983;52:711–60.

    Google Scholar 

  • Mohn GR, Ellenberger. Genetic effect of cyclophosphamide, ifosfamide and trofosfamide. Mutat Res. 1976;32:334–60.

    Google Scholar 

  • Muscari MR, Caldarera CM, Guarnieri C. Age-dependent production of mitochondrial hydrogen peroxide, lipid peroxides and fluorescent pigments in the rat heart. Basic Res Cardiol. 1990;85:172–8.

    Google Scholar 

  • Pryor WA, Godber SS. Noninvasive measures of oxidative stress status in humans. Free Rad Biol Med. 1991;10:177–84.

    Google Scholar 

  • Raleigh JE. Radioprotection of membranes. Phamacol Ther. 1985;39:109–13.

    Google Scholar 

  • Reiter RJ. Functional pleiotropy of the neurohormone melatonin: antioxidant protection and neuroendocrine regulation. Front Neuroendocrinol. 1995;16:383–415.

    Google Scholar 

  • Reiter RJ. Melatonin and human reproduction. Ann Med. 1998;30:103–8.

    Google Scholar 

  • Reiter RJ, Tan DX, Manchester LC, Qi W. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of evidence. Cell Biochem Biophys. 2001;34:237–56.

    Google Scholar 

  • Schneider EL, Sternberg H, Tice RR. The analysis of cellular replication. Proc Natl Acad Sci USA. 1977;74:2041–4.

    Google Scholar 

  • Sies H. Oxidative stress. London: Academic Press; 1985:1–8.

    Google Scholar 

  • Sies H and Stahl W. Vitamin E and C, β-carotene and other carotenoids as antioxidants. Am J Clin Nutr. 1995;62:1315S–21S.

    Google Scholar 

  • Tan DX, Manchester LC, Reiter RJ, Qi WB, Karbownik M, Calvo JR. Significance of melatonin in antioxidative defense system: reactions and products. Biol Signals Recept. 2000;9:137–59.

    Google Scholar 

  • Waldhauzer F, Kovacs J, Reiter E. Age-related changes in melatonin levels in humans and its potential consequences for sleep disorders. Exp Gerontol. 1998;33:759–72.

    Google Scholar 

  • Yu HS, Tsin ATC, Reiter RJ. Melatonin: history, biosynthesis and assay methodology. In: Yu HS, Reiter RJ, eds. Melatonin, biosynthesis, physiological effects, and clinical applications. Boca Raton: CRC Press; 1993:1–16.

    Google Scholar 

  • Zhdanova IV, Cantor ML, Leclair OU. Behavioral effect of melatonin treatment in non-human primates. Sleep Res Online. 1998;1:114–18.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A.L. Bhatia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Manda, K., Bhatia, A. Prophylactic action of melatonin against cyclophosphamide-induced oxidative stress in mice. Cell Biol Toxicol 19, 367–372 (2003). https://doi.org/10.1023/B:CBTO.0000013342.17370.16

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:CBTO.0000013342.17370.16

Navigation