title: Localization of cytokines in heart ventricular and apex tissues exposed to sustained delivery of AED, T, and DHT using a rat model.
abstract: Studies have shown that endogenous estrogen minimized cellular injury at the organ level; however, very little research was done to determine the effects of endogenous androgens such as Testosterone (T), Dihydrotestosterone, (DHT), and Androstenedione (AED) on the cardiovascular system at the cellular level Studies targeted at establishing such effects will broaden our understanding of the roles played by these male steroid hormones on the cardiovascular system. Our objective therefore was to (1) Use a Rat model and sustained delivery of physiological levels of these hormones to (1) evaluate pathophysiological effects on the cardiovascular system; and (2) localized cytokines such as IL-1, IL-6 and TNF on these tissues. Four groups of Sprague Dawley rats were included in the study. Group 1 animals served as control, groups II, III, and IV were treated with TCPL drug delivery devices containing 40 mg each of T, DHT, and AED, respectfully. Animals were sacrificed after 90 days of exposure. The ventricles and apex were immunostained for IL-1, IL-6, TNF and were also stained with Hemotoxylin and Eosin for histopathological evaluation. Results showed that TCPL drug delivery systems released 5 ng/ml/day of T, and 2 ng/ml/day of DHT and AED. IL-6 was expressed in the control heart ventricle and T, DHT, and AED reduced expression of the cytokine significantly after 90 days. Very small number of cells from the apex responded to IL-6 than cells within the ventricles. The results revealed that (i) the exposure of sustained levels of androgenic hormones exhibited myocardial hypertrophic condition compared to the control animals, (ii) the control animals had a two-fold increase in the ventricles IL-6 production over T treated animals and approximately five-fold increase over DHT and AED treated animals, and (iii) other inflammatory cytokines IL-1 and TNF were not differentially expressed in the ventricles of experimental animals when compared with the control; and (iv) In the apex tissue, animals treated with AED exhibited cells with increased response to IL-6 and a decrease cells responding to TNF and IL-1. IL-6 production in the ventricles decreased in animals exposed to sustained androgenic steroids and this decrease could possibly lead to increased blood flow, resulting in better oxygenation of the myocardium and improved cardiac function.
authors.affiliation: University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Shontell L
authors.initials: SL
authors.lastname: Credit
authors.forename: Hamed A
authors.initials: HA
authors.lastname: Benghuzzi
authors.forename: Michelle
authors.initials: M
authors.lastname: Tucci
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Farah
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Cameron
mesh_terms: D000735:Androstenedione / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D016207:Cytokines / Q000032:analysis*; D013196:Dihydrotestosterone / Q000008:administration & dosage / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism*; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D009206:Myocardium / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000008:administration & dosage / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione