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

Abstract

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 (ΔΨm) 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, ΔΨm, and H₂O₂ production. ND significantly impaired mitochondrial Ca²⁺ influx in the heart, and ΔΨm 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 ΔΨm, and redox homeostasis being early mechanistic substrates for inducing heart and liver tissue damage.

Keywords: Mitochondrial calcium dynamics; Mitochondrial membrane potential; Nandrolone; Redox status; Testosterone.