Melatonin attenuates estradiol-induced oxidative damage to DNA: Relevance for cancer prevention

Malgorzata Karbownik, Russel J Reiter, Susanne Burkhardt, Eloisa Gitto, Dun Xian Tan, Andrzej Lewiñski

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Estrogens exert pro-oxidative effects and have been shown to damage DNA, potentially leading to cancer. Melatonin is a well-known antioxidant, free radical scavenger, and oncostatic agent. Changes in the levels of 8-oxo-7,8-dihydro-2′deoxyguanosine (8-oxodGuo), an index of DNA damage, and the levels of malondialdehyde + 4-hydroxyalkenals, an index of lipid peroxidation, were measured in kidneys, liver, and testes from hamsters treated with E2 (75 mg/kg body wt) and were collected 3 or 5 hr later. Other animals were treated with melatonin (15 mg/kg body wt, 30 min before and 120 min after E2 treatment) or were given both compounds. Additionally, lipid peroxidation was measured in liver homogenates exposed to ferrous sulfate (15 μM) in vitro. E2 treatment caused an increase in 8-oxodGuo levels in kidneys collected 5 hr after E2 administration, and in liver 3 hr after estrogen treatment. Melatonin completely prevented E2-induced DNA damage in both organs. Melatonin alone or when given with E2 and examined 3 hr later decreased the base level of 8-oxodGuo in testes. A tendency for a reduction in in vivo lipid peroxidation was observed after treatment of hamsters with either melatonin, E2, or both compounds, with a statistically significant decrease being measured in the liver following E2 administration. In vitro exposure to iron significantly enhanced lipid peroxidation in hepatic homogenates from untreated, melatonin-treated, or E2-injected hamsters; in the hepatic homogenates of hamsters given both E2 and melatonin, ferrous sulfate failed to augment lipid peroxidation. Our results confirm the dual actions of estrogens relative to oxidative damage, i.e., estrogen increases oxidative destruction of DNA while reducing lipid peroxidation. Melatonin had antioxidative actions in reducing oxidative damage to both DNA and to membrane lipids. Melatonin completely prevented the damaging action of E2 on DNA and synergized with the steroid to reduce lipid peroxidation.

Original languageEnglish (US)
Pages (from-to)707-712
Number of pages6
JournalExperimental Biology and Medicine
Volume226
Issue number7
StatePublished - 2001

Fingerprint

Melatonin
DNA Damage
Estradiol
Lipid Peroxidation
DNA
ferrous sulfate
Lipids
Cricetinae
Liver
Neoplasms
Estrogens
Testis
Kidney
Free Radical Scavengers
Membrane Lipids
Malondialdehyde
Animals
Iron
Antioxidants
Steroids

Keywords

  • DNA damage
  • Estrogen
  • Hamster
  • Kidney
  • Lipid peroxidation
  • Liver
  • Melatonin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Karbownik, M., Reiter, R. J., Burkhardt, S., Gitto, E., Tan, D. X., & Lewiñski, A. (2001). Melatonin attenuates estradiol-induced oxidative damage to DNA: Relevance for cancer prevention. Experimental Biology and Medicine, 226(7), 707-712.

Melatonin attenuates estradiol-induced oxidative damage to DNA : Relevance for cancer prevention. / Karbownik, Malgorzata; Reiter, Russel J; Burkhardt, Susanne; Gitto, Eloisa; Tan, Dun Xian; Lewiñski, Andrzej.

In: Experimental Biology and Medicine, Vol. 226, No. 7, 2001, p. 707-712.

Research output: Contribution to journalArticle

Karbownik, M, Reiter, RJ, Burkhardt, S, Gitto, E, Tan, DX & Lewiñski, A 2001, 'Melatonin attenuates estradiol-induced oxidative damage to DNA: Relevance for cancer prevention', Experimental Biology and Medicine, vol. 226, no. 7, pp. 707-712.
Karbownik, Malgorzata ; Reiter, Russel J ; Burkhardt, Susanne ; Gitto, Eloisa ; Tan, Dun Xian ; Lewiñski, Andrzej. / Melatonin attenuates estradiol-induced oxidative damage to DNA : Relevance for cancer prevention. In: Experimental Biology and Medicine. 2001 ; Vol. 226, No. 7. pp. 707-712.
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