Sinapic acid ameliorates paracetamol-induced acute liver injury through targeting oxidative stress and inflammation.

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.

• Authors: Amir Rostami, Tourandokht Baluchnejadmojarad, Mehrdad Roghani
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 49 Issue 6 Pg. 4179-4191 (Jun 2022) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 35279777 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature B.V.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Coumaric Acids
• NF-E2-Related Factor 2
• NF-kappa B
• Acetaminophen
• sinapinic acid
• Sirtuin 1

Topics

• Acetaminophen (adverse effects)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Chemical and Drug Induced Liver Injury (drug therapy, pathology)
• Coumaric Acids
• Inflammation (pathology)
• Liver (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Oxidative Stress
• Sirtuin 1