Neuroprotective and Antiapoptotic Effects of Allopregnanolone and Curcumin on Arsenic-Induced Toxicity in SH-SY5Y Dopami
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Neurophysiology, Vol. 52, No. 2, March, 2020
Neuroprotective and Antiapoptotic Effects of Allopregnanolone and Curcumin on Arsenic-Induced Toxicity in SH-SY5Y Dopaminergic Human Neuroblastoma Cells H. Khodadadi,1 G. P. Jahromi,2 G. Zaeinalifard3, M. Fasihi-Ramandi,4 M. Esmaeili,3 and A. Shahriary5 Received July 28, 2019 Parkinson’s disease (PD) is a widespread neurological disorder mainly characterized by gradual death of dopaminergic neurons in the basal ganglia. In our study, we compared the effects of curcumin (Curc) as a herbal medicine and those of allopregnanolone (Allo) as a synthetic drug on arsenic(Ars-)induced toxicity in an SH-SY5Y in vitro model of PD. Cell survival was determined by the MTT assay; intracellular reactive oxygen species (ROSs) and the mitochondrial potential were assessed by a fluorescence probe. Furthermore, immunoblotting was applied to determine the biomarkers of cells apoptosis. As was found, Ars decreases the cell survival rate and enhances the loss of the mitochondrial membrane potential. The mean contents of intracellular ROSs, amount of c-Fos, and caspase-3 ratio significantly increased in Ars-exposed cells. Pretreatment of cells with Allo (250 µM) and Curc (5 μM) significantly decreased mean levels of these factors in Ars-treated cells. Although Curc showed a greater protective effect than Allo, the respective difference was statistically insignificant. The neuroprotective effects of Allo and Curc are probably related to their antioxidant and anti-apoptotic properties, which suggests their therapeutic potential in PD treatment.
Keywords: Parkinson’s disease, arsenic, SH-SY5Y cells, allopregnanolone, curcumin, apoptosis.
INTRODUCTION Since the industrial revolution, various industrial toxic chemicals have widely spread into the human life cycle. Simultaneously, the prevalence of neuroendocrine diseases, such as Parkinson’s disease (PD), has risen dramatically. PD is one of the most common motor disorders, which occurs throughout the world in all ethnic groups and both genders. The incidence of PD is about 15 per 100,000 in the general population, rising to 160 per 100,000 in the age group over 65 years [1]. Moreover, PD is more prevalent in men than in women [2].
Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. 2,4,5 Baqiyatallah University of Medical Sciences (2Neuroscience Research Center, 4Molecular Research Center, and 5Chemical Injuries Research Center, Systems Biology and Poisonings Institute), Tehran, Iran. 3 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. Correspondence should be addressed to A. Shahriary (e-mail: [email protected]) or G. P. Jahromi (e-mail: [email protected]). 1
The dopaminergic pathway of the nigro-striatal system plays a substantial role in functional organization of the brain basal ganglia. A clear proof of this is the severe motor deficit in PD patients because of the degenerative changes in this system [
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