Dose-dependent toxic effects of high-dose estrogen on renal and cardiac injury in surgically postmenopausal mice
| Autor: | James J. Yang, Xiao Ping Yang, Tang Dong Liao, Fangfei Wang, Xiangguo Dai, Martin A. D'Ambrosio, Xiaomei Meng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Ovariectomy Blotting Western Hemodynamics Blood Pressure Kidney General Biochemistry Genetics and Molecular Biology Article chemistry.chemical_compound Mice Internal medicine medicine Albuminuria Animals Myocardial infarction General Pharmacology Toxicology and Pharmaceutics Hydronephrosis Creatinine Dose-Response Relationship Drug Estradiol business.industry Estrogen Replacement Therapy Uterus Glomerulosclerosis Estrogens Heart General Medicine Organ Size medicine.disease Postmenopause Oxidative Stress Endocrinology medicine.anatomical_structure Blood pressure chemistry Heart Function Tests Female medicine.symptom business |
| Popis: | 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 effects on the heart. Main methods Ovariectomized (ovx) mice received either placebo (P) or E2 at 0.02 (E2-L, low dose), 0.42 (E2-M, moderate dose) or 4.2 μg/d (E2-H, high dose) for 8 weeks. Key findings E2-L partially restored uterine weight and plasma estrogen levels without affecting heart, lung and liver weight, hemodynamic parameters, or heart and kidney morphology and function. E2-M restored normal uterine weight, but this was accompanied by a significant increase in kidney weight, albuminuria, glomerular matrix formation and markers for oxidative stress. E2-H increased uterine weight 4.5-fold and resulted in higher plasma creatinine levels, severe albuminuria, renal tubular dilatation, tubulointerstitial injury, hydronephrosis, glomerulosclerosis and oxidative stress. E2-H also caused ascites, hepatomegaly and fluid retention in the uterine horns but had no significant effect on blood pressure or heart function. Significance Our data demonstrated that an excessive dose of E2 that raises uterine weight beyond physiological levels adversely affects the kidney even before it damages the heart. We believe estrogen dosage should be taken into account when considering hormonal replacement therapy, since inappropriate doses of E2 may damage not only the heart but also the kidney. |
| Databáze: | OpenAIRE |
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