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Brain Res Bull. 2019 Aug 28;153:181-190. doi: 10.1016/j.brainresbull.2019.08.019. [Epub ahead of print]

Dehydroepiandrosterone alleviates oxidative stress and apoptosis in iron-induced epilepsy via activation of Nrf2/ARE signal pathway.

Author information

1
Neurobiology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
2
Department of Developmental Neurogenetics, Medical University of South Carolina, Charleston, SC, USA.
3
Neurobiology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India. Electronic address: sharmadeepakjnu@gmail.com.

Abstract

Epilepsy is a neurological disorder characterized by the prevalence of spontaneous and recurrent seizures. Oxidative stress has been recognized as an intrinsic mechanism for the initiation and progression of epilepsy. In the present study, we investigated the neuroprotective effect of dehydroepiandrosterone (DHEA) against iron-induced epilepsy in rats. Animals were made epileptic by intracortical injection of FeCl3 (5 μl of 100 mM), and DHEA (30 mg/kg b. wt., for 7, 14, and 21 days) was administered intraperitoneally. The results showed electrophysiological alterations, excessive oxidative damage, diminished antioxidant defence and induction of apoptosis in the cortex and hippocampus of epileptic rats. Expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO-1) was downregulated in both brain regions. While, DHEA treatment for 14 and 21 days has counteracted oxidative stress, reduced neuronal apoptosis and improved electrophysiological changes along with upregulation of Nrf2, HO-1, and NQO-1. In conclusion, our findings demonstrate that neuroprotective effect of DHEA against iron-induced epilepsy might be escorted by the alleviation of oxidative stress through Nrf2-mediated signal pathway.

KEYWORDS:

Antioxidant enzymes; Apoptosis; Dehydroepiandrosterone; Epilepsy; Oxidative stress; Seizures

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