Abstract
Protective effects of boswellic acid (BA) against acetaminophen (APAP)-induced hepatotoxicity in Balb/ cA mice were examined. BA, at 0.05 or 0.1%, was supplied for 4 weeks. Acute liver injury was induced by APAP treatment. Results showed that BA intake increased hepatic BA bioavailability. APAP treatment decreased glutathione (GSH) level, increased reactive oxygen species (ROS) and oxidized glutathione (GSSG) production; and lowered activity and protein expression of glutathione reductase (GR) and heme oxygenase (HO)-1 in liver. BA intake at both doses alleviated subsequent APAP-induced oxidative stress by retaining GSH content, decreasing ROS and GSSG formations, reserving activity and expression of GR and HO-1 in liver, and lowering hepatic cytochrome P450 2E1 activity and expression. APAP treatment enhanced hepatic levels of interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1. BA pre-intake diminished APAP-induced release of those inflammatory cytokines and chemokines. APAP upregulated hepatic protein expression of toll-like receptor (TLR)-3, TLR-4, MyD88, nuclear factor kappa B (NF-κB) p50, NF-κB p65 and JNK. BA pre-intake at both doses suppressed the expression of NF-κB p65 and p-JNK, and only at 0.1% down-regulated hepatic TLR-3, TLR-4 and MyD88 expression. APAP led to obvious foci of inflammatory cell infiltration in liver, determined by H&E stain. BA intake at both doses attenuated hepatic inflammatory infiltration. These findings support that boswellic acid is a potent hepatoprotective agent.
Highlights
Acetaminophen (APAP, called paracetamol) is a widely used analgesic and antipyretic drug
The activation of toll-like receptor (TLR)-3 and TLR-4 has been implicated in APAP-induced hepatic damage because both TLRs could stimulate the production of adaptor proteins including MYD88 and nuclear factor kappa B (NF-țB), which in turn promote the generation of oxidants and inflammatory cytokines and chemokines [7, 8]
After blocking with a protein solution containing 5% skim milk for 1 h, membranes were treated with monoclonal antibody (BoehringerMannheim, Indianapolis, IN, USA) against heme oxygenase (HO)-1, CYP2E1 (1:1000), NF-țB p50, NF-țB p65, JNK (1:500), TLR-3, TLR-4, MyD88 (1:2000) at 4oC overnight, and followed by incubating with horseradish peroxidase-conjugated antibody at room temperature for 3.5 h
Summary
Acetaminophen (APAP, called paracetamol) is a widely used analgesic and antipyretic drug. Any agent with the ability to reserve GSH, inhibit CYP2E1 activity and/or lower inflammatory cytokines and chemokines may potentially attenuate APAP related liver injury. It is highly possible that BA intake or supplement could increase its accumulation in liver, and further enhance hepatic defensive capability to prevent or attenuate liver injury The purpose of this animal study was to examine the protective effects and action modes of BA at various doses upon liver of acetaminophen treated mice. The influence of this compound upon GSH, ROS and cytokines variation, CYP2E1 activity and protein expression of associated factors such as NF-țB, TLR-3 and TLR-4 was evaluated. Histological analysis was processed in order to provide more solid evidence to support the benefit of using BA as a hepatic protective agent
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