Lactobacillus plantarum C88 protects against aflatoxin B1-induced liver injury in mice via inhibition of NF-\u03baB\u2013mediated inflammatory responses and excessive apoptosis

Li Huang,Jingbo Xu,Ge Yang,Cuicui Duan,Zijian Zhao,Chao Wang,Yujuan Zhao,Shengyu Li,Lei Gao,Chunhua Niu

doi:10.1186/s12866-019-1525-4

Abstract

BackgroundProbiotics play an important role in the human and animal defense against liver damage. However, the protective mechanism of Lactobacillus plantarum C88 on chronic liver injury induced by mycotoxin remains unclear.ResultsIn this study, the addition of L. plantarum C88 obviously ameliorated the increased contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total cholesterol and triglyceride, the diminish contents of total protein and albumin in serum of mice challenged with AFB1. Simultaneously, L. plantarum C88 attenuated the inflammatory response via significantly reducing the levels of pro-inflammatory factors, including interleukin-1β (IL-1β), IL-6, IL-8, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in serum. Furthermore, L. plantarum C88 remarkably down-regulated the nuclear factor kappa B (NF-κB) signaling pathways by weakening the expression of toll-like receptor 2 (TLR2) and TLR4, and inhibited NF-κB nuclear translocation through enhancing the expression of NF-κB inhibitor (IκB). Neutralization experiments confirmed that L. plantarum C88 decreased the levels of some pro-inflammatory factors due to the suppression of the NF-κB signaling pathways. Besides, L. plantarum C88 decreased the levels of Bax and Caspase-3, elevated the level of Bcl-2, and reduced mRNA expressions of Fatty acid synthetase receptor (Fas), FAS-associated death domain (FADD), TNF receptor associated death domain (TRADD) and Caspase-8 in the liver.ConclusionsProbiotic L. plantarum C88 prevented AFB1-induced secretion of pro-inflammatory cytokines by modulating TLR2/NF-κB and TLR4/NF-κB pathways. The molecular mechanisms of L. plantarum C88 in ameliorating AFB1-induced excessive apoptosis included regulating the mitochondrial pathway and cell death receptor pathways.

Highlights

Probiotics play an important role in the human and animal defense against liver damage
L. plantarum C88 decreased the levels of Bax and Caspase-3, elevated the level of Bcl-2, and reduced mRNA expressions of Fatty acid synthetase receptor (Fas), FASassociated death domain (FADD), TNF receptor associated death domain (TRADD) and Caspase-8 in the liver
Mehrzad et al [3] found that Aflatoxin B1 (AFB1) activates toll-like receptor 2 (TLR2) and Toll-like receptor (TLR4), which trigger the Nuclear factor kappa B (NF-κB) signaling pathway that leads to the synthesis and secretion of tumor necrosis factor-α (TNF-α), IL-1β, IL-6 and other pro-inflammatory cytokines in murine pure primary astrocytes

Summary

Introduction

Probiotics play an important role in the human and animal defense against liver damage. The protective mechanism of Lactobacillus plantarum C88 on chronic liver injury induced by mycotoxin remains unclear. As an important detoxification organ, the liver is continuously exposed to certain adverse factors such as alcohol, fat, pathogens and cellular metabolites, which can cause liver injury, hepatitis and liver degradation. AFB1 is a metabolite of Aspergillus flavus and A. parasiticus, which is classified under Group I carcinogenic agents by International Agency for Research on Cancer (IARC) [2], and is a potent hepatotoxic and hepatic carcinogenic mycotoxin in humans. The mechanisms of AFB1-induced liver injury are complex, and previous studies have shown that inflammatory response is a critical step in the process. It is necessary to find safe and effective natural anti-inflammatory agents for preventing or alleviating AFB1-induced hepatic injury

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