| Autor: |
do Nascimento, A. M., de Lima, E. M., Boëchat, G. A. P., Meyrelles, S. D. S., Bissoli, N. S., Lenz, D., Endringer, D. C., de Andrade, T. U. |
| Předmět: |
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| Zdroj: |
Human & Experimental Toxicology; Nov2015, Vol. 34 Issue 11, p1139-1147, 9p, 1 Chart, 4 Graphs |
| Abstrakt: |
Anabolic androgenic steroids lead to cardiac complications and have been shown to exhibit proapoptotic effects in cardiac cells; however, the mechanism involved in those effects is unclear. The aim of this study was to assess whether apoptosis and the activation of caspase-3 (Casp-3) induced by testosterone in high concentrations involves increments in tumor necrosis factor-α (TNF-α) concentrations and angiotensin-converting enzyme (ACE) activity in cardiomyocytes (H9c2) cell cultures. Cardiomyocytes were treated with testosterone (5 × 10−6 mol/L), doxorubicin (9.2 × 10−6 mol/L), testosterone + etanercept (Eta; 6.67 × 10−5 mol/L), testosterone + losartan (Los; 10−7 mol/L), and testosterone + AC-DEVD-CHO (10−5 mol/L; Casp-3 inhibitor). Apoptosis was determined by flow cytometry and by the proteolytic activity of Casp-3. We demonstrated that incubation of H9c2 cells for 48 h with testosterone causes the apoptotic death of 60–70% of the cells and co-treatments with Eta, Los, or AC-DEVD-CHO reduced this effect. Testosterone also induces apoptosis (concentration dependent) and increases the proteolytic activity of Casp-3, which were reduced by co-treatments. TNF-α and ACE activities were elevated by testosterone treatment, while co-treatment with Los and Eta reduced these effects. We concluded that an interaction between testosterone, angiotensin II, and TNF-α induced apoptosis and Casp-3 activity in cultured cardiomyocytes, which contributed to the reduced viability of these cells induced by testosterone in toxic concentrations. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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