Ethanol Exacerbates Manganese-Induced Neurobehavioral Deficits, Striatal Oxidative Stress, and Apoptosis Via Regulation of p53, Caspase-3, and Bax/Bcl-2 Ratio-Dependent Pathway.

Abstract:

:This study investigated the effects of ethanol (EtOH) on manganese (Mn)-induced striatal toxicity in rat by evaluating the neurobehavioral changes, biochemical and molecular events in rats exposed to Mn alone at 30 mg/kg, or their combination with EtOH at 1.25- and 5-g/kg body weight for 35 consecutive days. Locomotive and exploratory profiles were assessed using a video tracking software (ANY-Maze software) during a 5-min trial in a novel environment. Subsequently, acetylcholinesterase (AChE) activity, oxidative stress markers, histological morphology, and expression of apoptotic proteins (p53 and Bax and caspase-3) and anti-apoptotic protein (Bcl-2) were assessed in the striatum. Results showed that Mn, EtOH, and their combination induced locomotor and motor deficits. Track plot analysis indicated that EtOH exacerbated the Mn-induced reduction in exploratory profiles of exposed rats. Similarly, exposure of rats to Mn, EtOH, or combination of Mn and EtOH resulted in decreased activities of anti-oxidant enzymes, diminished level of reduced glutathione, downregulated Bcl-2 expression, increased AChE activity, enhanced hydrogen peroxide and lipid peroxidation levels, and upregulated expressions of p53, Bax, and caspase-3. Moreover, potentiation of Mn-induced striatal toxicity by EtOH co-exposure was dose dependent. Taken together, it seems that EtOH exacerbates Mn-induced neurobehavioral deficits, oxidative stress, and apoptosis induction via the regulation of p53, caspase-3, and Bax/Bcl-2 ratio-dependent pathway in rat striatum.

journal_name

Biol Trace Elem Res

authors

Nkpaa KW,Awogbindin IO,Amadi BA,Abolaji AO,Adedara IA,Wegwu MO,Farombi EO

doi

10.1007/s12011-018-1587-4

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

135-148

issue

1

eissn

0163-4984

issn

1559-0720

pii

10.1007/s12011-018-1587-4

journal_volume

191

pub_type

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