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Pioglitazone alleviates the mitochondrial apoptotic pathway and mito‐oxidative damage in the d ‐galactose‐induced mouse model
Author(s) -
Prakash Atish,
Kumar Anil
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12144
Subject(s) - pioglitazone , oxidative stress , morris water navigation task , apoptosis , endocrinology , chemistry , medicine , galactose , pharmacology , biochemistry , diabetes mellitus , hippocampus , type 2 diabetes
SummaryChronic injection of d ‐galactose can cause gradual deterioration in learning and memory capacity, and activates oxidative stress, mitochondrial dysfunction and apoptotic cell death in the brain of mice. Thus, it serves as an animal model of ageing. Recent evidence has shown that mild cognitive impairment in humans might be alleviated by treatment with piogliatzone (peroxisome proliferator‐activated receptor gamma ( PPAR γ) agonists). To continue exploring the effects of piogliatzone in this model, we focused on behavioural alteration, oxidative damage, mitochondrial dysfunction and apoptosis in d ‐galactose‐induced mice. The ageing model was established by administration of d ‐galactose (100 mg/kg) for 6 weeks. Pioglitazone (10 and 30 mg/kg) and bisphenol A diglycidyl ether (15 mg/kg) were given daily to d ‐galactose‐induced senescent mice. The cognitive behaviour of mice was monitored using the Morris water maze. The anti‐oxidant status and apoptotic activity in the ageing mice was measured by determining mito‐oxidative parameters and caspase‐3 activity in brain tissue. Systemic administration of d ‐galactose significantly increased behavioural alterations, biochemical parameters, mitochondrial enzymes, and activations of caspase‐3 and acetylcholinesterase enzyme activity as compared with the control group. Piogliatzone treatment significantly improved behavioural abnormalities, biochemical, cellular alterations, and attenuated the caspase‐3 and acetylcholinesterase enzyme activity as compared with the control. Furthermore, pretreatment of BADGE ( PPAR γ antagonist) with pioglitazone reversed the protective effect of pioglitazone in d ‐galactose‐induced mice. The present study highlights the protective effects of pioglitzone against d ‐galactose‐induced memory dysfunction, mito‐oxidative damage and apoptosis through activation of PPAR γ receptors. These findings suggest that pioglitazone might be helpful for the prevention or alleviation of ageing.