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Metformin long-term use alleviates age-dependent oxidative stress and improves neurocognitive function in non-diabetic aged rats
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Enam Alhagh Charkhat Gorgich   , Houman Parsaie , Seyed Jamal Hosseini , Maryam Sarbishegi |
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Abstract: (262 Views) |
Introduction: Aging is an inevitable physiological process, associated with a decline in cognitive function and many functional disabilities. It has been shown that metformin increases life expectancy and improves clinical outcomes in diabetic patients. Studies are paying increasing attention to metformin's anti-aging properties. Oxidative stress is a prominent factor in age-associated diseases. Thus, the purpose of the study was to investigate the effects of metformin long-term use on age-dependent oxidative stress and cognitive function.
Methods and Materials: In this experimental study, 32 non-diabetic male Wistar rats were randomly divided into control (Ctrl) and metformin (Met) groups (n=16). In the Met group, 100 mg/kg of Met was added to drinking water daily for six months and the Ctrl received no treatment. After 6 months of Met administration, behavioral, biochemical, and histological evaluations were performed on the hippocampus. The shuttle box test was used for the passive avoidance task in 24-month-old rats. To the biochemical analysis, the malondialdehyde (MDA) content and the total antioxidant capacity (TAC) were detected. Nissl and TUNEL staining were also used for histopathological assessments. Data were analyzed using an independent t-test.
Results: The findings demonstrated that Met significantly reduced the MDA content and enhanced the TAC in the hippocampus of the Met group (p<0.05). The survival of hippocampal CA1 neurons was significantly higher in the Met group as compared to the Ctrl group, while the number of TUNEL-positive neurons decreased significantly (p<0.05). On the other hand, Met markedly boosted the passive avoidance memory in the Met group as compared to the Ctrl group (p<0.05).
Conclusion: These findings suggest that Met long-term intake, by modulating the oxidant/antioxidant mechanisms, prevents the loss of hippocampal neurons caused by age-dependent oxidative stress and improves neurocognitive functions in aged rats. Our findings also extend our understanding of Met's effects on aging processes.
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| Keywords: Metformin, Oxidative stress, Aging, Hippocampus, Antioxidants |
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Full-Text [PDF 266 kb]
(45 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2023/12/15 | Accepted: 2023/08/23 | Published: 2023/08/23
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