2011
DOI: 10.1016/j.lfs.2010.11.008
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Dose-dependent toxic effects of high-dose estrogen on renal and cardiac injury in surgically postmenopausal mice

Abstract: Aims-We previously found that in mice with experimental myocardial infarction (MI), 17β-estradiol (E2) increased mortality and worsened cardiac remodeling and these deleterious effects were associated with renal enlargement and hydronephrosis in a dose-dependent manner. In the present study we questioned whether E2-induced renal damage predisposes to rather than results from its adverse effectson the heart. Key findings-E2-L partially restored uterine weight and plasma estrogen levels without affecting heart, … Show more

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Cited by 21 publications
(17 citation statements)
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“…Current observations also reveal that a high dose of E 2 exerts reproductive toxic effects such as a decrease in the size of the reproductive tract and follicle losses before the antral stage after PND5, which is different from previous reports [3,5]. It may be because of the toxic effects of E 2 treatment [38].…”
Section: Discussioncontrasting
confidence: 91%
“…Current observations also reveal that a high dose of E 2 exerts reproductive toxic effects such as a decrease in the size of the reproductive tract and follicle losses before the antral stage after PND5, which is different from previous reports [3,5]. It may be because of the toxic effects of E 2 treatment [38].…”
Section: Discussioncontrasting
confidence: 91%
“…Baylis [14] reported that estrogens protect women against kidney damage and endothelial damage by maintaining a higher level of renal NO than in men. Meng et al [23] on the contrary found that highdose estrogen supplementation was toxic and contributed to the development of cardiac and renal injury. Furthermore, estradiol supplementation in foetal rats caused renal damage, which was synergistically increased by alcohol supplementation but this was not found when testosterone supplementation occurred [45].…”
Section: Discussionmentioning
confidence: 99%
“…Maric et al [21,22] found that estradiol supplementation attenuated renal disease in rats and that the rate of diabetic renal disease progression in women is slower than in men. However, Meng et al [23] found that high doses of estrogen exerted a toxic effect on renal and cardiac injury in surgically menopausal mice.…”
Section: Introductionmentioning
confidence: 99%
“…We recently reported that in mice with intact cardiac function or myocardial infarction, low-dose estrogen tended to be cardioprotective whereas at higher doses that increased plasma estradiol beyond the physiological levels, estrogen increased mortality, worsened cardiac function and caused severe damage to the kidney, including hydronephrosis, severe albuminuria, renal tubular dilatation and glomerulosclerosis. High dose of estrogen also caused ascites, hepatomegaly and fluid retention in the uterine horns [62 • ,63 •• ]. High doses of estrogen also raised testosterone significantly, although the mechanisms by which estrogen replacement increases testosterone are not clear.…”
Section: Hormonal Replacement Therapymentioning
confidence: 99%