Advances in Gerontology

, Volume 8, Issue 4, pp 328–338 | Cite as

Circadian Rhythms of Antioxidant Enzyme’s Activity in Young and Adult Rats under Light Deprivation Conditions

  • E. A. KhizhkinEmail author
  • V. A. Ilyukha
  • I. A. Vinogradova
  • E. P. Antonova
  • A. V. Morozov


We have studied the age-related features of circadian rhythms of superoxide dismutase (SOD) and catalase activity in the liver of rats under conditions of light deprivation. In standard light conditions (LD), significant daily fluctuations in SOD activity with a maximum at 7:00 a.m. were detected only in young animals (1.5 months) while catalase activity was observed in both young animals (1.5 months) and adults (7.5 months) with peak at 4:00 a.m. The daily dynamics of total and specific activity of SOD and catalase in the liver of young and adult rats differed, depending on the period of ontogeny in which the impact of light deprivation had begun. When females after giving birth and their offspring were moved to darkness (group LD/DD), the circadian rhythms of SOD and catalase activities were found in the young rats and were absent in adult rats. However, circadian rhythms of the antioxidant enzymes (AOE) activities were inherent only in adult rats when light deprivation impacted on pregnant females (group DD/DD). Changes in circadian rhythms under light deprivation were characterized either by a phase shift of the enzymes activity (in LD/DD group) or by a violation of their development in ontogeny (in DD/DD group). With aging a significant decrease of catalase activity was compensated by an increase in the amplitude of circadian rhythms of this enzyme activity in animals of all groups. The presence of an ultradian rhythm in the general circadian cycle characterized by a second peak with a smaller amplitude and shorter period can be considered a distinctive feature of daily fluctuations in AOЕ activity in young rats in LD and LD/DD groups.


diurnal (circadian) rhythms antioxidant enzymes light deprivation rats ontogeny 



  1. 1.
    Anisimov, V.N., Molekulyarnye i fiziologicheskie mekhanizmy stareniya (Molecular and Physiological Mechanisms of Aging), St. Petersburg: Nauka, 2008, vol. 1.Google Scholar
  2. 2.
    Rukovodstvo po laboratornym zhivotnym i al’ternativnym modelyam v biomeditsinskikh issledovaniyakh (Manual on Laboratory Animals and Alternative Models in Biomedical Studies), Karkishchenko, N.N. and Grahcev, S.V., Eds., Moscow: Profil’, 2010.Google Scholar
  3. 3.
    Eticheskaya ekspertiza biomeditsinskikh issledovanii: prakticheskie rekomendatsii (Ethical Expertise of Biomedical Studies: Practical Manual), Belousov, Yu.B., Ed., Moscow: Ross. O-vo Klin. Issled., 2005.Google Scholar
  4. 4.
    Albarrán, M. T., López-Burillo, S., Pablos, M.I., et al., Endogenous rhythms of melatonin, total antioxidant status and superoxide dismutase activity in several tissues of chick and their inhibition by light, J. Pineal Res., 2001, vol. 30, no. 4, pp. 227–233.Google Scholar
  5. 5.
    Antolín, I., Rodríguez, C., and Saínz, R.M., Neurohormone melatonin prevents cell damage: effect on gene expression for antioxidant enzymes, FASEB J., 1996, vol. 10, no. 8, pp. 882–890.Google Scholar
  6. 6.
    Bass, J. and Takahashi, J.S., Circadian integration of metabolism and energetics, Science, 2010, vol. 330, no. 6009, pp. 1349–1354.CrossRefGoogle Scholar
  7. 7.
    Bears, R.F. and Sizer, I.N., A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase, J. Biol. Chem., 1952, vol. 195, no. 1, pp. 133–140.Google Scholar
  8. 8.
    Benot, S., Molinero, P., Soutto, M., et al., Circadian variations in the rat serum total antioxidant status: correlation with melatonin levels, J. Pineal Res., 1998, vol. 25, no. 1, pp. 1–4.CrossRefGoogle Scholar
  9. 9.
    Benot, S., Goberna, R., Reiter, R.J., et al., Physiological levels of melatonin contribute to the antioxidant capacity of human serum, J. Pineal Res., 1999, vol. 27, no. 1, pp. 59–64.CrossRefGoogle Scholar
  10. 10.
    Berra, B. and Rizzo, A.M., Melatonin: circadian rhythm regulator, chronobiotic, antioxidant and beyond, Clin. Dermatol., 2009, vol. 27, no. 2, pp. 202–209.CrossRefGoogle Scholar
  11. 11.
    Bonnefont-Rousselot, D. and Collin, F., Melatonin: action as antioxidant and potential applications in human disease and aging, Toxicology, 2010, vol. 278, no. 1, pp. 55–67.CrossRefGoogle Scholar
  12. 12.
    Borjigin, J., Zhang, L.S., and Calinescu, A.A., Circadian regulation of pineal gland rhythmicity, Mol. Cell. Endocrinol., 2012, vol. 349, no. 1, pp. 13–19.CrossRefGoogle Scholar
  13. 13.
    Brooks, E. and Canal, M.M., Development of circadian rhythms: role of postnatal light environment, Neurosci. Biobehav. Rev., 2013, vol. 37, no. 4, pp. 551–560.CrossRefGoogle Scholar
  14. 14.
    Calvo, J. and Boya, J., Postnatal evolution of the rat pineal gland: light microscopy, J. Anat., 1984, vol. 138, no. 1, pp. 45–53.Google Scholar
  15. 15.
    Christ, E., Korf, H.-W., and von Gall, C., When does it start ticking? Ontogenetic development of the mammalian circadian system, Prog. Brain Res., 2012, vol. 199, pp. 105–118.CrossRefGoogle Scholar
  16. 16.
    Davis, F.C., Melatonin: role in development, J. Biol. Rhythms, 1997, vol. 12, pp. 498–508.CrossRefGoogle Scholar
  17. 17.
    Davis, F.C. and Gorski, R.A., Development of hamster circadian rhythms: role of the maternal suprachiasmatic nucleus, J. Comp. Physiol. A, 1988, vol. 162, no. 5, pp. 601–610.CrossRefGoogle Scholar
  18. 18.
    Deguchi, T., Ontogenesis of a biological clock for serotonin: acetyl coenzyme A N-acetyltransferase in pineal gland of rat, Proc. Natl. Acad. Sci. U.S.A., 1975, vol. 72, no. 7, pp. 2814–2818.CrossRefGoogle Scholar
  19. 19.
    Díaz-Muñoz, M., Hernández-Muñoz, R., Suárez, J., and Chagoya de Sánchez, V., Day-night cycle of lipid peroxidation in rat cerebral cortex and their relationship to the glutathione cycle and superoxide dismutase activity, Neuroscience, 1985, vol. 16, no. 4, pp. 859–863.Google Scholar
  20. 20.
    Farajnia, S., Deboer, T., and Rohling, J.H., Aging of the suprachiasmatic clock, Neuroscientist, 2014, vol. 20, no. 1, pp. 44–55.CrossRefGoogle Scholar
  21. 21.
    Froy, O., The circadian clock and metabolism, Clin. Sci., 2011, vol. 120, no. 2, pp. 65–72.CrossRefGoogle Scholar
  22. 22.
    Hardeland, R., Coto-Montes, A., and Poeggeler, B., Circadian rhythms, oxidative stress, and antioxidative defense mechanisms, Chronobiol. Int., 2003, vol. 20, no. 6, pp. 921–962.CrossRefGoogle Scholar
  23. 23.
    Hardeland, R., Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance, Endocrine, 2005, vol. 27, no. 2, pp. 119–130.CrossRefGoogle Scholar
  24. 24.
    Husse, J., Eichele, G., and Oster, H., Synchronization of the mammalian circadian timing system: light can control peripheral clocks independently of the SCN clock: alternate routes of entrainment optimize the alignment of the body’s circadian clock network with external time, BioEssays, 2015, vol. 37, no. 10, pp. 1119–1128.CrossRefGoogle Scholar
  25. 25.
    Ikegami, T., Maruyama, Y., Doi, H., et al., Ultradian oscillation in expression of four melatonin receptor subtype genes in the pineal gland of the grass puffer, a semilunar-synchronized spawner, under constant darkness, Front. Neurosci., 2015, vol. 30, pp. 1–10.Google Scholar
  26. 26.
    Jang, Y.S., Lee, M.H., Lee, S.H., and Bae, K., Cu/Zn superoxide dismutase is differentially regulated in period gene-mutant mice, Biochem. Biophys. Res. Commun., 2011, vol. 409, no. 1, pp. 22–27.CrossRefGoogle Scholar
  27. 27.
    Lacoste, M.G., Ponce, I.T., Golini, R.L., et al., Aging modifies daily variation of antioxidant enzymes and oxidative status in the hippocampus, Exp. Gerontol., 2017, vol. 88, pp. 42–50.CrossRefGoogle Scholar
  28. 28.
    Landgraf, D., Koch, C.E., and Oster, H., Embryonic development of circadian clocks in the mammalian suprachiasmatic nuclei, Front. Neuroanat., 2014, vol. 8, pp. 1–10.CrossRefGoogle Scholar
  29. 29.
    Liu, T. and Borjigin, J., Free-running rhythms of pineal circadian output, J. Biol. Rhythms, 2005, vol. 20, no. 5, pp. 430–440.CrossRefGoogle Scholar
  30. 30.
    Lowry, O.H., Rosenbrough, N.J., Farr, A.L., and Randall, R.J., Protein measurement with the Folin phenol reagent, J. Biol. Chem., 1951, vol. 193, no. 1, pp. 265–275.Google Scholar
  31. 31.
    Manikonda, P.K. and Jagota, A., Melatonin administration differentially affects age-induced alterations in daily rhythms of lipid peroxidation and antioxidant enzymes in male rat liver, Biogerontology, 2012, vol. 13, no. 5, pp. 511–524.CrossRefGoogle Scholar
  32. 32.
    Martin, V., Sainz, R.M., Mayo, J.C., et al., Daily rhythm of gene expression in rat superoxide dismutases, Endocr. Res., 2003, vol. 29, no. 1, pp. 83–95.CrossRefGoogle Scholar
  33. 33.
    Mirmiran, M., Swaab, D.F., Kok, J.H., et al., Circadian rhythms and the suprachiasmatic nucleus in perinatal development, aging and Alzheimer’s disease, Prog. Brain Res., 1992, vol. 93, pp. 151–162.CrossRefGoogle Scholar
  34. 34.
    Misra, H.H. and Fridovich, I., The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase, J. Biol. Chem., 1972, vol. 247, no. 10 P. 3170–3175.Google Scholar
  35. 35.
    Miyata, R., Tanuma, N., Sakuma, H., and Hayashi, M., Circadian rhythms of oxidative stress markers and melatonin metabolite in patients with xeroderma pigmentosum group A, Oxid. Med. Cell. Longevity, 2016, vol. 2016. doi 10.1155/2016/5741517Google Scholar
  36. 36.
    Pablos, M.I., Reiter, R.J., Ortiz, G.G., et al., Rhythms of glutathione peroxidase and glutathione reductase in brain of chick and their inhibition by light, Neurochem. Int., 1998, vol. 32, no. 1, pp. 69–75.CrossRefGoogle Scholar
  37. 37.
    Pandi-Perumal, S.R., BaHammam, A.S., Brown, G.M., et al., Melatonin antioxidative defense: therapeutical implications for aging and neurodegenerative processes, Neurotoxic. Res., 2013, vol. 23, no. 3, pp. 267–300.CrossRefGoogle Scholar
  38. 38.
    Pereira, B., Rosa, L.F., Safi, D.A., et al., Hormonal regulation of superoxide dismutase, catalase, and glutathione peroxidase activities in rat macrophages, Biochem. Pharmacol., 1995, vol. 50, no. 12, pp. 2093–2098.CrossRefGoogle Scholar
  39. 39.
    Pevet, P. and Challet, E., Melatonin: both master clock output and internal time-giver in the circadian clocks network, J. Physiol. (Paris), 2011, vol. 105, nos. 4–6, pp. 170–182.Google Scholar
  40. 40.
    Reiter, R.J., Rosales-Corral, S., Coto-Montes, A., et al., The photoperiod, circadian regulation and chronodisruption: the requisite interplay between the suprachiasmatic nuclei and the pineal and gut melatonin, J. Physiol. Pharmacol., 2011, vol. 62, no. 3, pp. 269–274.Google Scholar
  41. 41.
    Reiter, R.J., Tan, D.-X., Korkmaz, A., and Rosales-Corral, S.A., Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology, Hum. Reprod. Update, 2014, vol. 20, no. 2, pp. 293–307.CrossRefGoogle Scholar
  42. 42.
    Reppert, S.M., Weaver, D.R., and Rivkees, S.A., Prenatal function and entrainment of a circadian clock, in Research in Perinatal Medicine, Vol. 9: Development of Circadian Rhythmicity and Photoperiodism in Mammals, Reppert, S.M., Ed., Ithaca, NY: Perinatology Press, 1989, ch. 2, pp. 25–44.Google Scholar
  43. 43.
    Reppert, S.M. and Schwartz, W.J., Maternal coordination of the fetal biological clock in utero, Science, 1983, vol. 220, no. 4600, pp. 969–971.CrossRefGoogle Scholar
  44. 44.
    Rowe, S.A. and Kennaway, D.J., Melatonin in rat milk and the likelihood of its role in postnatal maternal entrainment of rhythms, Am. J. Physiol.-Regul., Integr. Comp. Physiol., 2002, vol. 282, no. 3, pp. R797–R804.CrossRefGoogle Scholar
  45. 45.
    Sancar, A., Lindsey-Boltz, L.A., Kang, T.H., et al., Circadian clock control of the cellular response to DNA damage, FEBS Lett., 2010, vol. 584, no. 12, pp. 2618–2625.CrossRefGoogle Scholar
  46. 46.
    Sani, M., Sebaï, H., Gadacha, W., et al., Catalase activity and rhythmic patterns in mouse brain, kidney and liver, Comp. Biochem. Physiol., Part B: Biochem. Mol. Biol., 2006, vol. 145, nos. 3–4, pp. 331–337.Google Scholar
  47. 47.
    Sanchez, S., Paredes, S.D., Martin, M.I., et al., Effect of tryptophan administration on circulating levels of melatonin and phagocytic activity, J. Appl. Biomed., 2004, vol. 2, no. 3, pp. 169–177.Google Scholar
  48. 48.
    Sumova, A., Sladek, M., Polidarova, L., et al., Circadian sys tem from conception till adulthood, Prog. Brain Res., 2012, vol. 199, pp. 83–103.CrossRefGoogle Scholar
  49. 49.
    Tan, D.-X., Reiter, R.J., Manchester, L.C., et al., Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger, Curr. Top. Med. Chem., 2002, vol. 2, no. 2, pp. 181–197.CrossRefGoogle Scholar
  50. 50.
    Tapia-Osorio, A., Salgado-Delgado, R., Angeles-Castellanos, M., and Escobar, C., Disruption of circadian rhythms due to chronic constant light leads to depressive and anxiety-like behaviors in the rat, Behav. Brain Res., 2013, vol. 252, pp. 1–9.CrossRefGoogle Scholar
  51. 51.
    Tomas-Zapico, C., Coto-Montes, A., Martinez-Fraga, J., et al., Effects of continuous light exposure on antioxidant enzymes, porphyric enzymes and cellular damage in the Harderian gland of Syrian hamster, J. Pineal. Res., 2003, vol. 34, no. 1, pp. 60–68.CrossRefGoogle Scholar
  52. 52.
    Wilking, M., Ndiaye, M., Mukhtar, H., and Ahmad, N., Circadian rhythm connections to oxidative stress: implications for human health, Antioxid. Redox Signaling, 2013, vol. 19, no. 2, pp. 192–208.CrossRefGoogle Scholar
  53. 53.
    Xu, Y.-Q., Zhang, D., Jin, T., et al., Diurnal variation of hepatic antioxidant gene expression in mice, PLoS One, 2012, vol. 7, no. 8. doi doi 10.1371/journal.pone.0044237Google Scholar
  54. 54.
    Yamazaki, S., Yoshikawa, T., Biscoe, E.W., et al., Ontogeny of circadian organization in the rat, J. Biol. Rhythms, 2009, vol. 24, no. 1, pp. 55–63.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • E. A. Khizhkin
    • 1
    • 2
    Email author
  • V. A. Ilyukha
    • 1
  • I. A. Vinogradova
    • 2
  • E. P. Antonova
    • 1
  • A. V. Morozov
    • 1
  1. 1.Institute of Biology, Karelian Research Centre, Russian Academy of SciencesPetrozavodskRussia
  2. 2.Petrozavodsk State UniversityPetrozavodskRussia

Personalised recommendations