Metformin ameliorates the age-related changes of d-galactose administration in ovariectomized mice

Fundam Clin Pharmacol. 2018 Aug;32(4):392-399. doi: 10.1111/fcp.12364. Epub 2018 Apr 23.

Abstract

Metformin (Met) has been shown to have pleiotropic effects such as neuroprotective, antioxidant, and anti-inflammatory properties making that a potential candidate for the treatment of central nervous system (CNS) disorders. This study was designed to investigate the possible effect of Met on the d-galactose (d-gal)-induced aging in ovariectomized mice. The female mice underwent bilateral ovariectomy. d-gal was administered orally at a dose of 500 mg/kg, and Met was administrated orally at doses of 1 and 10 mg/kg for 6 weeks. Anxiety-like behavior was evaluated by the elevated plus-maze. Physical power was assessed by vertical grid holding test and forced swimming capacity test. The brains were assessed for the level of superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). Ovariectomy caused anxiety and declined the physical power as well as BDNF and SOD levels. d-gal administration in ovariectomized mice exacerbated these deleterious effects. Met hampered the anxiety-like behavior and strengthened the physical power of d-gal-treated ovariectomized mice. Met also increased the SOD and BDNF levels in the brains of d-gal-treated ovariectomized animals. Based on the obtained results, we suggest Met administration as a novel therapeutic approach for the treatment of age-related conditions in the absence of female sex hormones.

Keywords: aging; d-galactose; metformin; ovariectomy.

MeSH terms

  • Aging / drug effects*
  • Aging / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Brain / drug effects
  • Brain / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • Female
  • Galactose / pharmacology*
  • Maze Learning / drug effects
  • Metformin / pharmacology*
  • Mice
  • Neuroprotective Agents / pharmacology
  • Ovariectomy / methods
  • Superoxide Dismutase / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Brain-Derived Neurotrophic Factor
  • Neuroprotective Agents
  • Metformin
  • Superoxide Dismutase
  • Galactose