title: High-dose testosterone and dehydroepiandrosterone induce cardiotoxicity in rats: Assessment of echocardiographic, morphologic, and oxidative stress parameters.
abstract: The aim of this study is to assess cardiotoxic effect of testosterone (TES) and dehydroepiandrosterone (DHEA) in Sprague Dawley rats. We compared the impact of subacute (14 days) and subchronic (90 days) administration of suprapharmacologic doses of TES and DHEA on body weight, locomotor activity, muscle strength, echocardiographic parameters, heart histopathology, and oxidative stress markers with the control group. Testosterone (10, 30, and 100 mg/100 g body weight) and DHEA (10 mg/100 g body weight) administration decreased the body weights and locomotor activity (p < 0.05), and the combination of both increased muscle strength (p < 0.05) in rats. In our histopathological evaluation, misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in high-dose TES (100 mg/100 g)-treated rats, especially on day 14. On day 90, mild changes such as misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in TES and DHEA-treated groups. According to our echocardiographic study on day 14 and day 90, TES, especially at high doses, induced increase in left ventricular posterior wall diameter and ejection fraction (p < 0.05). In this study, blood oxidative stress marker malondialdehyde was increased slightly but not significantly in TES and DHEA groups. On the other hand, antioxidant enzymes such as SOD and glutathione peroxidase (GSH-Px) levels were slightly but not significantly increased in TES and DHEA groups. These data demonstrate that the potential risk to cardiac health due to exogenous androgen use may be related to oxidative stress in rats.
authors.affiliation: Institute of Forensic Sciences, Ankara University, Dikimevi-Ankara, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Emer
authors.affiliation: Department of Pharmacology, Gülhane Faculty of Medicine, Ankara, Turkey oyildiz@gata.edu.tr.
authors.forename: O
authors.initials: O
authors.lastname: Yildiz
authors.affiliation: Department of Pharmacology, Gülhane Faculty of Medicine, Ankara, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Seyrek
authors.affiliation: Department of Cardiology, Gülhane Faculty of Medicine, Ankara, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Demirkol
authors.affiliation: Department of Physiology, Gülhane Faculty of Medicine, Ankara, Turkey.
authors.forename: T
authors.initials: T
authors.lastname: Topal
authors.affiliation: Department of Pathology, Gülhane Faculty of Medicine, Ankara, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Kurt
authors.affiliation: Center of Pharmaceutical Sciences, Gülhane Medical Academy, Ankara, Turkey.
authors.forename: A
authors.initials: A
authors.lastname: Sayal
mesh_terms: D000728:Androgens / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D066126:Cardiotoxicity; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D006321:Heart / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017208:Rats, Wistar; D013739:Testosterone / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000728:Androgens; D013739:Testosterone; D003687:Dehydroepiandrosterone
keywords: Testosterone; cardiovascular toxicity; dehydroepiandrosterone; oxidative stress; pathology; rat