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Melatonin Attenuates Arsenic-Induced Neurotoxicity in Rats Through the Regulation of miR-34a/miR-144 in Sirt1/Nrf2 Pathway

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A Correction to this article was published on 03 January 2024

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Abstract

Arsenic (As) exposure is known to cause several neurological disorders through various molecular mechanisms such as oxidative stress, apoptosis, and autophagy. In the current study, we assessed the effect of melatonin (Mel) on As-induced neurotoxicity. Thirty male Wistar rat were treated daily for 28 consecutive days. As (15 mg/kg, gavage) and Mel (10 and 20 mg/kg, i.p.) were administered to rats. Morris water maze test was done to evaluate learning and memory impairment in training days and probe trial. Oxidative stress markers including MDA and GSH levels, SOD activity, and HO-1 levels were measured. Besides, the levels of apoptosis (caspase 3, Bax/Bcl2 ratio) and autophagy markers (Sirt1, Beclin-1, and LC3 II/I ratio) as well as the expression of miR-144 and miR-34a in cortex tissue were determined. As exposure disturbed learning and memory in animals and Mel alleviated these effects. Also, Mel recovered cortex pathological damages and oxidative stress induced by As. Furthermore, As increased the levels of apoptosis and autophagy proteins in cortex, while Mel (20 mg/kg) decreased apoptosis and autophagy. Also, Mel increased the expression of miR-144 and miR-34a which inhibited by As. In conclusion, Mel administration attenuated As-induced neurotoxicity through anti-oxidative, anti-apoptotic, and anti-autophagy mechanisms, which may be recommended as a therapeutic target for neurological disorders.

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Abbreviations

AChE:

Acetyl choline esterase

Bax:

Bcl-2-associated X protein

BBB:

Blood brain barrier

Bcl-2:

B-cell lymphoma 2

BSA:

Bovine serum albumin

cDNA:

Complementary DNA

CT:

Cycle threshold

DTNB 5:

5′-dithiobis 2-nitrobenzoic acid

EDTA:

Ethylene diamine tetraacetic acid

EGTA:

Ethylene glycol tetraacetic acid

GSH:

Glutathione

H&E:

Hematoxylin and eosin

HO-1:

Heme oxygenase-1

LC3:

Microtubule-associated protein 1 light chain 3

LPS:

Lipopolysaccharide

MDA:

Malondialdehyde

Mel:

Melatonin

ml:

Milliliter

miR:

MicroRNA

mTOR:

Mechanistic target of rapamycin

MWM:

Morris water maze

Nrf2:

Nuclear factor-carotenoid 2 related factor 2

PBS:

Phosphate buffer saline

PIC:

Phosphatase inhibitor cocktail

PMSF:

Phenylmethylsulfonyl fluoride

PVDF:

Polyvinylidene fluoride

ROS:

Reactive oxygen species

SD:

Standard deviation

SDS:

Sodium dodecyl sulfate

Sirt1:

Sirtuin

SOD:

Superoxide dismutase

TBA:

Thiobarbituric acid

TBST:

Tris buffered saline tween

TMED:

Tetramethylethylenediamine

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Funding

This work was funded by Mashhad University of Medical Science, Mashhad, Iran.

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Authors and Affiliations

  1. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Nahid Najafi, Samira Barangi, Soghra Mehri & Gholamreza Karimi

  2. Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran

    Zahra Moosavi

  3. Bioinformatics Research Group, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Hamid Aghaee-Bakhtiari

  4. Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Hamid Aghaee-Bakhtiari

  5. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Gholamreza Karimi

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  1. Nahid Najafi
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Conceptualization: Gholamreza Karimi and Soghra Mehri; methodology: Gholamreza Karimi, Soghra Mehri, Nahid Najafi, Samira Barangi, Zahra Moosavi, and Seyed Hamid Aghaee-Bakhtiari; software: Nahid Najafi and Samira Barangi; investigation: Nahid Najafi; data curation: Nahid Najafi; writing—original draft and writing—review and editing: Nahid Najafi, Gholamreza Karimi, and Soghra Mehri; supervision and project administration: Gholamreza Karimi and Soghra Mehri; funding acquisition: Gholamreza Karimi. All authors have read and agreed to the published version of the manuscript.

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Najafi, N., Barangi, S., Moosavi, Z. et al. Melatonin Attenuates Arsenic-Induced Neurotoxicity in Rats Through the Regulation of miR-34a/miR-144 in Sirt1/Nrf2 Pathway. Biol Trace Elem Res 202, 3163–3179 (2024). https://doi.org/10.1007/s12011-023-03897-5

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