Melatonin ameliorates arsenic‐induced cardiotoxicity through the regulation of the Sirt1/Nrf2 pathway in rats

Yarmohammadi, Fatemeh; Barangi, Samira; Aghaee‐Bakhtiari, Seyed Hamid; Hosseinzadeh, Hossein; Moosavi, Zahra; Reíter, Russel J.; Hayes, A. Wallace; Mehri, Soghra; Karimi, Gholamreza

doi:10.1002/biof.1934

Cited by 18 publications

(12 citation statements)

References 82 publications

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“…For extracting hepatic proteins, homogeneous buffer prepared according to previous study. [ 44 ] The protease inhibitor cocktail (Sigma, P8340), and phenylmethylsulfonyl fluoride (PMSF) were added to 100 mg of liver tissue and homogenized. Following sonication, the homogenate was centrifuged at 10,000 g for 10 min (4°C).…”

Section: Methodsmentioning

confidence: 99%

“…[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). Rats in the high-dose melatonin group were given 30 mg/kg of melatonin intraperitoneally for 28 days.…”

Section: Experimental Design and Treatmentmentioning

confidence: 99%

“…[69] Moreover, the enhancement of Sirt1, Beclin-1 and the LC3 II/I ratio in the heart and aorta of rats treated with arsenic has been reported to be reversed by melatonin. [13,44] Recently, several studies have suggested that the regulation of microRNAs such as miR-122 and miR-21 may be one of the basic mechanisms of arsenic in autophagy adjustment. [26,27] For example, Liu et al proposed that the exposure of human hepatic epithelial cells (L-02) to arsenic resulted in the overexpression of miR-21 and consequently induced autophagy through enhanced Beclin-1 and the LC3 II/I ratio, suggesting arsenic liver toxicity is associated with autophagy activity.…”

Section: Effect Of Arsenic and Melatonin On Mir-34a Expression In Rat...mentioning

confidence: 99%

“…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: Experimental Design and Treatmentmentioning

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%

Section: Experimental Design and Treatmentmentioning

confidence: 99%

Section: Effect Of Arsenic and Melatonin On Mir-34a Expression In Rat...mentioning

confidence: 99%

Section: Experimental Design and Treatmentmentioning

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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“…Sirtuin 1 (silent information regulator 1; Sirt1) is a kind of deacetylase, which plays a pivotal role in the regulation of oxidative stress, calorie restriction/energetics, inflammation, endothelial functions, cell senescence, autophagy, and apoptosis due to its effect on the post-transcriptional modifications of proteins such as p53, FoxO1, Nrf2, and NF-κB (Haigis and Sinclair, 2010; Hwang et al, 2013; Yarmohammadi et al, 2023). Sirt1 is sensitive to the cell metabolic and redox situations and modulates cell hemostasis and autophagy pathway (Hwang et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

The effect of melatonin on benzo(a)pyrene-induced renal toxicity in mice

et al. 2023

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Benzo(a)pyrene is a ubiquitous environmental contaminant, which could induce renal injury. It is reported that melatonin has a protective effect against multiple organ injuries by regulating oxidative stress, apoptosis, and autophagy. The aim of this study was to estimate the melatonin effects on benzo(a)pyrene renal toxicity in mice and the possible molecular mechanisms involved in this model. Thirty male mice were allocated to five groups and treated with benzo(a)pyrene (75 mg/kg, oral gavage) and/or melatonin (10 and 20 mg/kg, intraperitoneally). The oxidative stress factors were evaluated in renal tissue. The levels of apoptotic (the Bax/Bcl-2 ratio and caspase-3) and autophagic (the LC3 II/I, Beclin-1, and Sirt1) proteins were examined using Western blot. Following the administration of benzo(a)pyrene, malondialdehyde, caspase-3 and the Bax/Bcl-2 ratio increased in renal tissue, while Sirt1, Beclin-1, and the LC3 II/I ratio diminished. Interestingly, the co-administration of 20 mg/kg melatonin along with benzo(a)pyrene reduced the oxidative stress markers, apoptotic and autophagic proteins. Collectively, melatonin exhibited a protective effect against benzo(a)pyrene-induced renal injury through the suppression of oxidative stress and apoptosis and the inhibition of Sirt1/autophagy pathway.

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The potential protective role of carotenoids from saffron: A focus on endoplasmic reticulum stress‐related organ damage

Mirzavi,

Rajabian,

Hosseini

2024

Food Science & Nutrition

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The anticancer, antioxidant, and immunomodulatory properties of carotenoids from saffron or apocarotenoids (e.g., crocin, safranal, crocetin, and picrocrocin) have prompted research into their benefits. Apocarotenoids seem to be effective compound for the treatment of chronic diseases, such as neurodegenerative, cardiovascular, cancer, respiratory, and metabolic disorders. Endoplasmic reticulum (ER) is an essential organelle found in the cytoplasm of eukaryotic cells that participates in the biosynthesis of proteins, lipids, and steroid hormones. Given the role of the ER in the regulation of several fundamental biological processes, including metabolic pathways and immune responses, aberrant ER function can have a significant influence on these vital processes and result in serious pathological consequences. Exposure of cell to adverse environmental challenges, such as toxic agents, ischemia, and so on, causes accumulation of unfolded or misfolded proteins in the ER lumen, also called ER stress. There is a growing evidence to suggest that ER disturbance in the form of oxidative/nitrosative stress and subsequent apoptotic cell death plays major roles in the pathogenesis of many human diseases, including cardiovascular diseases, diabetes mellitus, neurodegenerative diseases, and liver diseases. Apocarotenoids with their unique properties can modulate ER stress through PERK/eIF2α/ATF4/CHOP (protein kinase R (PKR)‐like ER kinase/eukaryotic initiation factor 2α/activating transcription factor 4/C/EBP /homologous protein) and X‐Box Binding Protein 1/activating transcription factor 6 (XBP1/ATF6) pathways. In addition, they suppress apoptosis through inhibition of endoplasmic and mitochondrial‐dependent caspase cascade and can stimulate SIRT1 (silent information regulator 1) and Nrf2 (nuclear factor erythroid 2‐related factor 2) expression, thereby leading to protection against oxidative stress. This review summarizes the potential benefits of apocarotenoids in various ER‐stress‐related disorders.

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Melatonin ameliorates arsenic‐induced cardiotoxicity through the regulation of the Sirt1/Nrf2 pathway in rats

Cited by 18 publications

References 82 publications

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

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

The effect of melatonin on benzo(a)pyrene-induced renal toxicity in mice

The potential protective role of carotenoids from saffron: A focus on endoplasmic reticulum stress‐related organ damage

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