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

Najafi, Nahid; Barangi, Samira; Moosavi, Zahra; Aghaee-Bakhtiari, Seyed Hamid; Mehri, Soghra; Karimi, Gholamreza

doi:10.1007/s12011-023-03897-5

Cited by 3 publications

(2 citation statements)

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“…In the arsenic group, sodium arsenite (NaAsO2, >96% purity; S7400; Sigma Company) was dissolved in deionized water, and rats were given 15 mg/kg sodium arsenite by oral gavage for 28 days. [ 13,29,44 ] In the arsenic plus melatonin groups, melatonin (>96% purity; sc‐207848, Santa Cruze Biotechnology Company) was dissolved in deionized water containing 2.5% absolute ethanol, and rats were given 10, 20, and 30 mg/kg melatonin intraperitoneally along with arsenic (15 mg/kg) for 28 days. [ 30,44 ] Rats in the control group received the vehicle of arsenic (deionized water; oral gavage) and melatonin (deionized water containing 2.5% absolute ethanol; intraperitoneally).…”

Section: Methodsmentioning

confidence: 99%

“…[ 26 ] The regulatory effect of arsenic on miR‐34a expression and following Sirt1 function was also reported in previous studies. [ 28,29 ] MiR‐34a is one of the numerous miRNAs that has been shown to suppress Sirt1 protein production in a variety of tissues and pathological contexts. [ 30 ] By attaching to the 3′‐UTR region of Sirt1 mRNA, miR‐34a represses the translation of Sirt1 in the liver and exacerbates the metabolic syndrome, similar to promotes inflammation and cellular senescence in vascular smooth muscle cells.…”

Section: Introductionmentioning

confidence: 99%

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Melatonin attenuates liver injury in arsenic‐treated rats: The potential role of the Nrf2/HO‐1, apoptosis, and miR‐34a/Sirt1/autophagy pathways

Barangi,

Mehri,

Moosavi

et al. 2024

J Biochem & Molecular Tox

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Arsenic is a toxic metalloid found in the environment in different organic and inorganic forms. Molecular mechanisms implicated in arsenic hepatotoxicity are complex but include oxidative stress, apoptosis, and autophagy. The current study focused on the potential protective capacity of melatonin against arsenic‐induced hepatotoxicity. Thirty‐six male Wistar rats were allocated into control, arsenic (15 mg/kg; orally), arsenic (15 mg/kg) plus melatonin (10, 20, and 30 mg/kg; intraperitoneally), and melatonin alone (30 mg/kg) groups for 28 days. After the treatment period, the serum sample was separated to measure liver enzymes (AST and ALT). The liver tissue was removed and then histological alterations, oxidative stress markers, antioxidant capacity, the levels of Nrf2 and HO‐1, apoptosis (Bcl‐2, survivin, Mcl1, Bax, and caspase‐3), and autophagy (Sirt1, Beclin‐1, and LC3 II/I ratio) proteins, as well as the expression level of miR‐34a, were evaluated on this tissue. Arsenic exposure resulted in the enhancement of serum AST, ALT, and substantial histological damage in the liver. Increased levels of malondialdehyde, a lipid peroxidation marker, and decreased levels of physiological antioxidants including glutathione, superoxide dismutase, and catalase were indicators of arsenic‐induced oxidative damage. The levels of Nrf2, HO‐1, and antiapoptotic proteins diminished, while proapoptotic and autophagy proteins were elevated in the arsenic group concomitant with a low level of hepatic miR‐34a. The co‐treatment of melatonin and arsenic reversed the changes caused by arsenic. These findings showed that melatonin reduced the hepatic damage induced by arsenic due to its antioxidant and antiapoptotic properties as well as its regulatory effect on the miR‐34a/Sirt1/autophagy pathway.

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Section: Methodsmentioning

confidence: 99%