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 E-2 (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 E-2 treatment) or were given both compounds. Additionally, lipid peroxidation was measured in liver homogenates exposed to ferrous sulfate (15 muM) in vitro. E-2 treatment caused an increase in 8-oxodGuo levels in kidneys collected 5 hr after E-2 administration, and in liver 3 hr after estrogen treatment. Melatonin completely prevented E-2-induced DNA damage in both organs. Melatonin alone or when given with E-2 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, E-2, or both compounds, with a statistically significant decrease being measured in the liver following E-2 administration. In vitro exposure to iron significantly enhanced lipid peroxidation in hepatic homogenates from untreated, melatonin-treated, or E-2-injected hamsters; in the hepatic homogenates of hamsters given both E-2 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 E-2 on DNA and synergized with the steroid to reduce lipid peroxidation.

Melatonin Attenuates Estradiol-Induced Oxidative Damage to DNA: Relevance for Cancer Prevention

GITTO, Eloisa;
2001-01-01

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 E-2 (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 E-2 treatment) or were given both compounds. Additionally, lipid peroxidation was measured in liver homogenates exposed to ferrous sulfate (15 muM) in vitro. E-2 treatment caused an increase in 8-oxodGuo levels in kidneys collected 5 hr after E-2 administration, and in liver 3 hr after estrogen treatment. Melatonin completely prevented E-2-induced DNA damage in both organs. Melatonin alone or when given with E-2 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, E-2, or both compounds, with a statistically significant decrease being measured in the liver following E-2 administration. In vitro exposure to iron significantly enhanced lipid peroxidation in hepatic homogenates from untreated, melatonin-treated, or E-2-injected hamsters; in the hepatic homogenates of hamsters given both E-2 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 E-2 on DNA and synergized with the steroid to reduce lipid peroxidation.
2001
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/1892045
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