Anabolic-androgenic steroids impair mitochondrial function and redox status in the heart and liver of mice

Supraphysiological doses of anabolic-androgenic steroids (AAS) may cause long-term functional abnormalities, particularly in the heart and liver, which may only represent the later-stage of the cumulative damage caused by dysfunctional organelles. We investigated whether mid-term supraphysiological doses of Testosterone and Nandrolone impair mitochondrial Ca2+ and membrane potential (Delta Psi m) dynamics, and redox machinery in the heart and liver of mice. CF1 albino mice were treated daily with 15 mg/kg of Nandrolone (ND) or Testosterone (T), or oil (vehicle) for 19 days. Preparations enriched in mitochondria from the heart or liver were used to perform assays of Ca2+ influx/efflux, Delta Psi m, and H2O2 production. ND significantly impaired mitochondrial Ca2+ influx in the heart, and Delta Psi m in both organs. ND and T increased H2O2 levels in the heart and liver relative to controls. Also, ND increased oxidative damage to lipids and proteins (TBARS and carbonyls) in the heart, and both AAS decreased glutathione peroxidase activity in the heart and liver. In summary, supraphysiological doses of ND, and in a lesser extend T, impaired mitochondrial Ca2+ influx and Delta Psi m, and redox homeostasis being early mechanistic substrates for inducing heart and liver tissue damage.