Alleviative effects from boswellic acid on acetaminophen-induced hepatic injury - Corrected and republished from: Biomedicine (Taipei). 2016 Jun; 6 (2): 9. doi: 10.7603/s40681-016-0009-1PMCID: PMC4864770.

Lung-Che Chen,Li-Hong Hu,Mei-Chin Yin

doi:10.1051/bmdcn/2017070207

Lung-Che Chen, Li-Hong Hu + Show 1 more

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https://doi.org/10.1051/bmdcn/2017070207

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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 up-regulated 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 hepato-protective 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-κB), which in turn promote the generation of oxidants and inflammatory cytokines and chemokines [7, 8]
Besides increasing GSH retention, we found that boswellic acid (BA) effectively decreased CYP2E1 activity and expression, lowered reactive oxygen species (ROS), tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1 production, as well as suppressed heme oxygenase (HO)-1, TLR-3, TLR-4, NF-κB p65 and p-JNK expression

Summary

Introduction

Acetaminophen (APAP, called paracetamol) is a widely used analgesic and antipyretic drug. It is metabolized by hepatic cytochrome P450 system, especially CYP2E1, which leads to the overproduction of reactive free radicals and n-acetyl-p-benzoquinoneimine (NAPQI) [1, 2]. It is well known that high doses of APAP deplete hepatic glutathione (GSH) because NAPQI reacts rapidly with GSH, which diminishes antioxidant defense, enhances oxidation stress, impairs liver functions, causes hepatocyte necrosis, and even promotes liver failure or death [3, 4]. The activation of 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-κB), which in turn promote the generation of oxidants and inflammatory cytokines and chemokines [7, 8]. Cavassani et al [9] reported that TLR-3 activation enhanced

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