Abstract
Purpose
In this study, we sought to find the effects and mechanisms of probiotic Lactobacillus casei Zhang (L. casei Zhang) on the pro-inflammatory cytokine production and hepatic inflammatory response in a rat model of acute liver failure induced by lipopolysaccharide (LPS) and d-galactosamine (GalN).
Methods
Male Wistar rats were orally administrated with or without L. casei Zhang for 30 days prior to challenge with LPS and GalN. Dexamethasone administrated group serving as a positive anti-inflammation control. Serum, intestinal and liver samples were collected 8 h after LPS/GalN challenge for histological, molecular and biochemical analysis.
Results
LPS/GalN challenge alone resulted in significantly increased production of endotoxin, tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β) and nitric oxide as compared to the normal control rats. Pretreatment with L. casei Zhang not only reduced these changes, but also attenuated hepatic inflammation as shown by improved histological assessment, decreased myeloperoxidase activity and reduced expression of IL-1β and inducible nitric oxide synthase in the liver. L. casei Zhang supplementation significantly inhibited LPS/GalN-triggered phosphorylation of ERK, JNK and p-38 MAPK, but increased the expression of TLR2, TLR9 and PPAR-γ. Moreover, L. casei Zhang treatment prevented intestinal injury and modulated the intestinal ecology by increasing the fecal Lactobacillus and Bifidobacterium levels.
Conclusions
Probiotic L. casei Zhang reduces LPS/GalN-induced pro-inflammatory cytokine and hepatic inflammation through modulating the TLR-MAPK-PPAR-γ signaling pathways and intestinal microbiota.
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Abbreviations
- ALF:
-
Acute liver failure
- GalN:
-
Galactosamine
- LPS:
-
Lipopolysaccharide
- MAPK:
-
Mitogen-activated protein kinase
- MPO:
-
Myeloperoxidase
- NF-κB:
-
Nuclear factor κB
- PPAR-γ:
-
Peroxisome proliferator-activated receptor gamma
- TLRs:
-
Toll-like receptors
- TNF-α :
-
Tumor necrosis factor-α
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Acknowledgments
We thank Dr. Kerong Zhang and Dr. Charles Hocart from Australian National University for revising the manuscript. This work was supported by grants from the National Natural Science Foundation of China (Grant No. 31270922, 81260662, 81360394), Inner Mongolia Natural Science Foundation (Grant No. 2012MS1156) and the Excellent Young Scientist Foundation of Inner Mongolia Agricultural University (Grant No. 2014XYQ-19).
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Yuzhen Wang, Jiming Xie and Yunxu Li have contributed equally to this article.
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Wang, Y., Xie, J., Li, Y. et al. Probiotic Lactobacillus casei Zhang reduces pro-inflammatory cytokine production and hepatic inflammation in a rat model of acute liver failure. Eur J Nutr 55, 821–831 (2016). https://doi.org/10.1007/s00394-015-0904-3
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DOI: https://doi.org/10.1007/s00394-015-0904-3