Abstract
Background
Acetaminophen (paracetamol, APAP) overdose is the principal cause of acute liver injury (ALI) that leads to liver failure typified with oxidative stress, mitochondrial and lysosomal dysfunction and with few antidotes for this condition. Therefore, more effective therapeutics are urgently required. Sinapic acid is a phenolic phytochemical with significant antioxidant, anti-inflammatory and hepatoprotective potential.
Rationale and purpose of the study
This study was conducted to evaluate hepatoprotective effect of this phytochemical in acetaminophen-induced model of ALI.
Methods and results
Male C57BL/6 mice were treated p.o. with sinapic acid (10 or 50 mg/kg) 3 times at 72, 24, and 1 h before APAP (300 mg/kg; i.p.) challenge. Functional factors of liver dysfunction were determined along with hepatic assessment of oxidative stress and inflammatory indexes and histopathological analysis was also conducted. Sinapic acid (50 mg/kg) properly decreased serum levels of ALT, ALP, and AST besides reducing liver level of ROS, MDA, IL-6, TNF-α, NF-kB, and MPO and improved sirtuin 1, HO-1, Nrf2, SOD activity, and MMP with no significant effect on IL-1β and catalase activity in addition to decreasing activity of lysosomal enzymes including cathepsin B and β-galactosidase. Also, sinapic acid at the higher dose ameliorated liver histopathological changes due to APAP and properly reversed NF-kB and Nrf2 immunoreactivity.
Conclusions
These findings show that sinapic acid pretreatment effectively protects liver against adverse and hepatotoxic effect of APAP through its antioxidant- and anti-inflammatory potential linked to NF-kB/Nrf2/HO-1 signaling and also via regulation of sirtuin 1, mitochondrial integrity, and lysosomal stabilization.
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Abbreviations
- ALI:
-
Acute liver injury
- ALT:
-
Alanine aminotransferase
- ALP:
-
Alkaline phosphatase
- APAP:
-
N-acetyl-para-aminophenol (Acetaminophen)
- AST:
-
Aspartate aminotransferase
- DCF-DA:
-
Dichlorofluorescein-diacetate
- GSH:
-
Glutathione
- HO-1:
-
Heme oxygenase 1
- IL-1β:
-
Interleukin-1β
- IL-6:
-
Interleukin-6
- MDA:
-
Malondialdehyde
- MMP:
-
Mitochondrial membrane potential
- MPO:
-
Myeloperoxidase
- NAPQI:
-
N-acetyl-para-benzo-quinone imine
- Nrf2:
-
Nuclear factor erythroid 2–related factor 2
- NF-kB:
-
Nuclear factor kappa-light-chain-enhancer of activated B cells
- ROS:
-
Reactive oxygen species
- SOD:
-
Superoxide dismutase
- TNFα:
-
Tumor necrosis factor α
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Acknowledgements
This research project was financially supported in 2019 by National Institute for Medical Research Development (NIMAD) of Iran (Grant number 987706).
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This article was funded by National Institute for Medical Research Development (987706).
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AR performed the experiments of the study. MR analyzed the data, supervised the study, and write the manuscript. TB helped in performing experiments and assisted in statistical analysis and manuscript preparation. All authors read and reviewed the final manuscript.
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All procedures of this study involving animals were approved by NIMAD Institute (Tehran, Iran) (IR.NIMAD.REC.1399.007) which were in compliance with NIH recommended guidelines.
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Rostami, A., Baluchnejadmojarad, T. & Roghani, M. Sinapic acid ameliorates paracetamol-induced acute liver injury through targeting oxidative stress and inflammation. Mol Biol Rep 49, 4179–4191 (2022). https://doi.org/10.1007/s11033-022-07251-1
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DOI: https://doi.org/10.1007/s11033-022-07251-1