Gemfibrozil protect PC12 cells through modulation of Estradiol receptors against oxidative stress

Introduction: neurodegenerative diseases are progressive disorders that could impair neuronal functions and structures. oxidative stress and mitochondrial dysfunction are involved in the etiology of neurodegenerative diseases such as alzheimer’s disease, parkinson’s disease and etc. gemfibrozil is used as a therapeutic drug for hyperlipidemia. it has been shown that gemfibrozil is neuroprotective via modulation of mitochondrial biogenesis pathway under oxidative stress condition and in a sex-dependent manner.materials and methods: in this study, neuronal-like pc12 cells with were pretreated with different concentrations of gemfibrozil and h2o2, concomitantly. results: in gemfibrozil pretreated groups, reduced level of caspase-3 and raised mitochondrial transcription factor a (tfam) levels were detected. in contrast, adding fulvestrant, an estradiol receptor antagonist, prevents the impact of gemfibrozil on oxidative stress condition, reducing its efficacy to protect the neurons against stress. conclusion: our results indicated the involvement of estradiol receptors in gemfibrozil neuroprotective mechanism, in diminishing oxidative stress-induced damage via reducing caspase-3 and inducing the level of tfam that plays a crucial role in the mitochondrial biogenesis.