Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES, Brazil.
Pharmaceutical Sciences Graduate Program, University Vila Velha, Vila Velha, ES, Brazil.
Steroids. 2021 Jun;170:108814. doi: 10.1016/j.steroids.2021.108814. Epub 2021 Mar 13.
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.
To investigate cardiac effects of OXA in low (LD) and high (HD) doses.
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.
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.
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.
临床实践中使用的氧雄龙（OXA），但其滥用情况频繁，包括青少年追求美学目标。然而，有害剂量对心血管系统的影响尚不清楚。
研究低（LD）和高（HD）剂量 OXA 对心脏的影响。
雄性 Wistar 青春期前大鼠分为 3 个实验组：对照组（CON）、LD 和 HD。只有 CON 组接受载体（羧甲基纤维素，0.5%），而 LD 和 HD 组分别通过灌胃接受 2.5 和 37.5mg/kg/天的 OXA，持续 4 周。评估血流动力学参数（+dP/dtmax、-dP/dtmin 和 Tau）和心脏自主神经张力。取出心脏进行组织学分析和氧化应激评估。通过 Western blot 测量钙处理蛋白的表达水平。
OXA 处理既不改变心脏收缩力，也不改变心脏自主神经张力。然而，观察到心脏肥大、胶原沉积和 ACE 表达增加呈剂量依赖性。此外，在 LD 和 HD 组中，p-磷酰化肌球蛋白结合蛋白（p-PLB）/PLB 比值分别观察到降低和升高；两组中的肌浆/内质网钙 ATP 酶 2a（SERCA2a）/PLB 比值均升高。OXA 仅在 LD 组中增加 SOD1 表达并降低过氧化氢酶表达，而在 HD 组中蛋白质氧化增加。
两种剂量的 OXA 均可促进病理性心脏重构，可能通过增加 ACE 来实现，而在 HD 治疗中这些作用加剧，而无论剂量如何，心脏收缩力均不受影响。
