Low and high doses of oxandrolone promote pathological cardiac remodeling in young male rats

Abstract

Oxandrolone (OXA) used in clinical practice, however, its misuse is frequent, including by adolescents pursuing an aesthetic goal. However, the impacts of noxious doses on the cardiovascular system remain unknown.

Aim: To investigate cardiac effects of OXA in low (LD) and high (HD) doses.

Methods: Male Wistar prepubescent rats were separated into 3 experimental groups: control (CON), LD, and HD. Only the CON group received the carrier (carboxymethylcellulose, 0.5%), while the LD and HD groups received, respectively, 2.5 and 37.5 mg/kg/day of OXA via gavage for 4 weeks. The hemodynamic parameters (+dP/dtmax, -dP/dtmin, and Tau) and cardiac autonomic tonus were assessed. Hearts were retrieved for histological analyses and oxidative stress evaluation. Expression levels of calcium-handling proteins were measured by western blot.

Results: The OXA treatment changed neither the cardiac contractility nor the cardiac autonomic tonus. However, cardiac hypertrophy, collagen deposition, and increased angiotensin-converting enzyme (ACE) expression were observed in a dose-dependent way. Also, the p-phospholamban (p-PLB)/PLB ratio was observed to decrease and increase, respectively, in the LD and HD groups; the sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a)/PLB ratio being higher in both groups. OXA increased SOD1 expression and decreased catalase expression only in the LD group, and protein oxidation was increased in HD.

Conclusion: Both doses of OXA could promote pathological cardiac remodeling, probably via increased ACE, and these effects were exacerbated in the HD treatment, but cardiac contractility was not affected regardless of the dose.

Keywords: Anabolic androgenic steroid; Angiotensin-converting enzyme; Cardiac contractility; Cardiac remodeling; Oxidative stress; Renin-angiotensin system.