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Metformin ameliorates the age‐related changes of d ‐galactose administration in ovariectomized mice
Author(s) -
Fatemi Iman,
Heydari Sara,
Kaeidi Ayat,
Shamsizadeh Ali,
Hakimizadeh Elham,
Khaluoi Amin,
Allahtavakoli Mohammad
Publication year - 2018
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12364
Subject(s) - ovariectomized rat , endocrinology , medicine , neurotrophic factors , behavioural despair test , neuroprotection , elevated plus maze , superoxide dismutase , central nervous system , hormone , hippocampus , oxidative stress , anxiety , antidepressant , receptor , psychiatry
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.