Ansari MA, Raish M, Bin Jardan YA, Ahmad A, Shahid M, Ahmad SF, Haq N, Khan MR, Bakheet SA. Sinapic acid ameliorates D-galactosamine/lipopolysaccharide-induced fulminant hepatitis in rats: Role of nuclear factor erythroid-related factor 2/heme oxygenase-1 pathways. World J Gastroenterol 2021; 27(7): 592-608 [PMID: 33642831 DOI: 10.3748/wjg.v27.i7.592]
Corresponding Author of This Article
Mushtaq Ahmad Ansari, PhD, Associate Professor, Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, King Khalid Road, Riyadh 11451, Saudi Arabia. muansari@ksu.edu.sa
Research Domain of This Article
Pharmacology & Pharmacy
Article-Type of This Article
Basic Study
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Ansari MA, Raish M, Bin Jardan YA, Ahmad A, Shahid M, Ahmad SF, Haq N, Khan MR, Bakheet SA. Sinapic acid ameliorates D-galactosamine/lipopolysaccharide-induced fulminant hepatitis in rats: Role of nuclear factor erythroid-related factor 2/heme oxygenase-1 pathways. World J Gastroenterol 2021; 27(7): 592-608 [PMID: 33642831 DOI: 10.3748/wjg.v27.i7.592]
World J Gastroenterol. Feb 21, 2021; 27(7): 592-608 Published online Feb 21, 2021. doi: 10.3748/wjg.v27.i7.592
Sinapic acid ameliorates D-galactosamine/lipopolysaccharide-induced fulminant hepatitis in rats: Role of nuclear factor erythroid-related factor 2/heme oxygenase-1 pathways
Mushtaq Ahmad Ansari, Mohammad Raish, Yousef A Bin Jardan, Ajaz Ahmad, Mudassar Shahid, Sheikh Fayaz Ahmad, Nazrul Haq, Mohammad Rashid Khan, Saleh A Bakheet
Mushtaq Ahmad Ansari, Sheikh Fayaz Ahmad, Mohammad Rashid Khan, Saleh A Bakheet, Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Mohammad Raish, Yousef A Bin Jardan, Mudassar Shahid, Nazrul Haq, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Ajaz Ahmad, Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Author contributions: Ansari MA and Raish M conceptualized the study; Ahmad A, Bin Jardan YA and Shahid M helped in the methodology; Shahid M did the formal analysis; Ahmad SF, Khan MR and Haq N helped in managing resources; Ansari MA, Raish M and Bakheet SA wrote the original first draft and supervised the study and the project was administered by Ansari MA; Shahid M and Raish M did the review, editing, and finalized the manuscript draft; Ansari MA acquired funding for this research.
Supported byDeanship of Scientific Research at King Saud University, No. RG-1439-083.
Institutional review board statement: The experiment proposal was authorized by the Ethics Committee of the Experimental Animal Care Society, King Saud University, Saudi Arabia (No. KSU-SE-20-13).
Institutional animal care and use committee statement: The experiment proposal was authorized by the Ethics Committee of the Experimental Animal Care Society, King Saud University, Saudi Arabia (No. KSU-SE-20-13).
Conflict-of-interest statement: The author declares that there are no conflicts of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Corresponding author: Mushtaq Ahmad Ansari, PhD, Associate Professor, Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, King Khalid Road, Riyadh 11451, Saudi Arabia. muansari@ksu.edu.sa
Received: October 26, 2020 Peer-review started: October 26, 2020 First decision: November 25, 2020 Revised: November 30, 2020 Accepted: January 21, 2021 Article in press: January 21, 2021 Published online: February 21, 2021 Processing time: 116 Days and 6.6 Hours
ARTICLE HIGHLIGHTS
Research background
Sinapic acid (SA) has been shown to have various pharmacological properties such as antioxidant, antifibrotic, anti-inflammatory, and anticancer activities. Its mechanism of action is dependent upon its ability to curb free radical production and protect against oxidative stress-induced tissue injuries.
Research motivation
In the current study, the hepatoprotective effects of SA against lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver failure (ALF) in rats were studied.
Research objectives
In the current study, the hepatoprotective effects of SA against LPS/D-GalN-induced acute liver failure (ALF) in rats were studied.
Research methods
Experimental ALF was induced with an intraperitoneal (i.p.) administration of 8 μg LPS and 800 mg/kg D-GalN in normal saline. SA was administered orally once daily starting 7 d before LPS/D-GalN treatment.
Research results
Data showed that SA ameliorates acute liver dysfunction, decreases serum levels of alanine transaminase (ALT), and aspartate aminotransferase (AST), as well as malondialdehyde (MDA) and NO levels in ALF model rats. However, pretreatment with SA (20 mg/kg and 40 mg/kg) reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and levels of inflammatory cytokines (tumor necrosis factor-α and interleukin 6). Also, SA increased the activity of the nuclear factor erythroid-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway.
Research conclusions
In conclusion, SA offers significant protection against LPS/D-GalN-induced ALF in rats by upregulating Nrf2/HO-1 and downregulating NF-κB.
Research perspectives
The amolearation of LPS/D-GalN-induced fulminant hepatitis through NRF2/HO-1 activation have been previously documented. However, the hepatoprotective effects of SA in LPS/D-GalN-induced fulminant hepatitis has not been previously investigated. To identify the detailed mechanisms of action for SA, we tested its antioxidant and anti-inflammatory activities in a rat model of LPS/D-GalN-induced fulminant hepatitis. Thus, the purpose of the current study was to explore the underlying hepatoprotective mechanism of SA against LPS/D-GalN-induced ALF in rats. We also aimed to identify its effects on ROS production, inflammation and apoptosis and the roles of Nrf2/HO-1 and NF-κB pathways.
