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N-Acetylcysteine Ameliorates Neurotoxic Effects of Manganese Intoxication in Rats: A Biochemical and Behavioral Study

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Abstract

Clinical and experimental evidences reveal that excess exposure to manganese is neurotoxic and leads to cellular damage. However, the mechanism underlying manganese neurotoxicity remains poorly understood but oxidative stress has been implicated to be one of the key pathophysiological features related to it. The present study investigates the effects associated with manganese induced toxicity in rats and further to combat these alterations with a well-known antioxidant N-acetylcysteine which is being used in mitigating the damage by its radical scavenging activity. The study was designed to note the sequential changes along with the motor and memory dysfunction associated with biochemical and histo-pathological alterations following exposure and treatment for 2 weeks. The results so obtained showed decrease in the body weights, behavioral deficits with increased stress markers and also neuronal degeneration in histo-pathological examination after manganese intoxication in rats. To overcome the neurotoxic effects of manganese, N-acetylcysteine was used in the current study due to its pleiotropic potential in several pathological ailments. Taken together, N-acetylcysteine helped in ameliorating manganese induced neurotoxic effects by diminishing the behavioral deficits, normalizing acetylcholinesterase activity, and augmentation of redox status.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

5-HT:

Serotonin

AChE:

Acetylcholinesterase

ANOVA:

Analysis of variance

BBB:

Blood brain barrier

BSA:

Bovine serum albumin

DTNB:

5,5’-Dithiobis (2-nitrobenzoic acid)

DTT:

Dithiothreitol

DA:

Dopamine

SOD:

Superoxide dismutase

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

GSH:

Reduced glutathione

GSSG:

Oxidized glutathione

TG:

Total glutathione

GST:

Glutathione transferase

H&E:

Hematoxylin and eosin

H2O2 :

Hydrogen peroxide

HPLC:

High performance liquid chromatography

i.p.:

Intraperitoneally

LPO:

Lipid peroxidation

LSD:

Least significance difference

MnCl2·4H2O:

Manganese chloride tetrahydrate

MnSOD:

Manganese superoxide dismutase

NBT:

Nitroblue tetrazolium

NAC:

N-acetylcysteine

PMF:

Post mitochondrial fraction

ROS:

Reactive oxygen species

SD:

Standard deviation

SPSS:

Statistical software package

TBA:

Thiobarbituric acid

TCA:

Trichloroacetic acid

SNpc:

Substantia nigra pars compacta

PD:

Parkinson’s disease

BBB:

Blood brain barrier

OH° :

Hydroxyl radical

O2°− :

Superoxide radical

H2O:

Water

MDA:

Malondialdehyde

O.D.:

Optical density

NADPH:

Nicotinamide adenine dinucleotide phosphate

CDNB:

2,4-Dinitrochlorobenzene

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Funding

This work was supported by UGC SAP, DST-FIST, PURSE New Delhi, India.

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Authors and Affiliations

  1. Department of Biophysics, Basic Medical Sciences Block II, Panjab University, Chandigarh, 160014, India

    Devika Chopra, Sheetal Sharma, Neha Sharma & Bimla Nehru

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  1. Devika Chopra
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  2. Sheetal Sharma
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  4. Bimla Nehru
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Correspondence to Bimla Nehru.

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All the protocols performed were approved by Animal Ethical Committee (IAEC) of Panjab University, Chandigarh, India with approval no. PU|45|99|CPCSEA|IAEC|2018|91.

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Chopra, D., Sharma, S., Sharma, N. et al. N-Acetylcysteine Ameliorates Neurotoxic Effects of Manganese Intoxication in Rats: A Biochemical and Behavioral Study. Neurochem Res 46, 1953–1969 (2021). https://doi.org/10.1007/s11064-021-03312-2

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