Effect of catecholestrogen administration during adriamycin-induced cardiomyopathy in ovariectomized rat.
The therapeutical beneficial effect of estrogen-derived metabolites or catecholestrogens is controversial. These molecules are produced during estrogen therapy based on 17-beta-estradiol treatment. The metabolization of 17-beta-estradiol is carried out in brain, kidney or liver, and triggers different products such as 2- and 4- hydroxyestradiol (2OH and 4OH). These products have shown antioxidant properties against oxidative stress (OS) in several experimental models. Different noxious side effects related to those metabolites have also been observed upon estrogen therapy. In this sense, catecholestrogens seem to be implicated in tumoral and mutagenic process after long treatment with estrogens substitutive therapy. In our study, we have verified that 2OH and 4OH have antioxidant and cardioprotective effects against adriamycin (AD)-induced cardiomyopathy in ovariectomized (OVX) rats. Catecholestrogens diminished the lipid peroxides and carbonyl protein (CO) content, and different enzymes related to cell injury (creatinine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase) in cardiac tissue from OVX-, AD-, and OVX+AD-treated rats. All these changes were correlated to a recovery on reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in heart tissue. The present study showed that 2OH and 4OH reduced all the parameters related to OS, antioxidant depletion and cardiac injury in OVX rats treated or not with AD.
Muñoz-Castañeda
J R
JR
Departament of Biochemistry and Molecular Biology, School of Medicine, University of Cordoba, Avda. Menéndez-Pidal s/n. C. P: 14004 Cordoba, Spain.
Túnez
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Muñoz
M C
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Bujalance
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Muntané
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Montilla
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D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D009202:Cardiomyopathies / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D002374:Catalase / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D004317:Doxorubicin; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002393:Estrogens, Catechol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000097:blood; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D002393:Estrogens, Catechol; D004958:Estradiol; D004317:Doxorubicin; C001390:2-hydroxyestradiol; C014036:4-hydroxyestradiol; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000410:Alanine Transaminase; D003402:Creatine Kinase