Systemic delivery of a mitochondria targeted antioxidant partially preserves limb muscle mass and grip strength in response to androgen deprivation

Mol Cell Endocrinol. 2021 Sep 15:535:111391. doi: 10.1016/j.mce.2021.111391. Epub 2021 Jul 7.

Abstract

Muscle mass is important for health. Decreased testicular androgen production (hypogonadism) contributes to the loss of muscle mass, with loss of limb muscle being particularly debilitating. Androgen replacement is the only pharmacological treatment, which may not be feasible for everyone. Prior work showed that markers of reactive oxygen species and markers of mitochondrial degradation pathways were higher in the limb muscle following castration. Therefore, we tested whether an antioxidant preserved limb muscle mass in male mice subjected to a castration surgery. Subsets of castrated mice were treated with resveratrol (a general antioxidant) or MitoQ (a mitochondria targeted antioxidant). Relative to the non-castrated control mice, lean mass, limb muscle mass, and grip strength were partially preserved only in castrated mice treated with MitoQ. Independent of treatment, markers of mitochondrial degradation pathways remained elevated in all castrated mice. Therefore, a mitochondrial targeted antioxidant may partially preserve limb muscle mass in response to hypogonadism.

Keywords: Hypogonadism; Muscle atrophy; Testosterone.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / pharmacology
  • Disease Models, Animal
  • Drug Delivery Systems
  • Hand Strength
  • Hypogonadism / drug therapy*
  • Hypogonadism / etiology
  • Male
  • Mice
  • Mitochondria / drug effects
  • Mitochondria, Muscle / drug effects
  • Mitochondria, Muscle / metabolism*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiology*
  • Orchiectomy / adverse effects
  • Organophosphorus Compounds / administration & dosage*
  • Organophosphorus Compounds / pharmacology
  • Resveratrol / administration & dosage*
  • Resveratrol / pharmacology
  • Ubiquinone / administration & dosage
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / pharmacology

Substances

  • Antioxidants
  • Organophosphorus Compounds
  • Ubiquinone
  • mitoquinone
  • Resveratrol