Probiotic Lactobacillus casei Zhang reduces pro-inflammatory cytokine production and hepatic inflammation in a rat model of acute liver failure

• Published in: European journal of nutrition Vol. 55; no. 2; pp. 821 - 831
• Main Authors: Wang, Yuzhen, Xie, Jiming, Li, Yunxu, Dong, Shichao, Liu, Huan, Chen, Junna, Wang, Yan, Zhao, Shimin, Zhang, Yong, Zhang, Heping
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2016; Springer Nature B.V
• Subjects: Acute Disease; animal models; Animals; anti-inflammatory activity; Anti-Inflammatory Agents - pharmacology; Bifidobacterium; blood serum; Chemistry; Chemistry and Materials Science; Cytokines - metabolism; dexamethasone; Dexamethasone - pharmacology; Disease Models, Animal; ecology; endotoxins; Extracellular Signal-Regulated MAP Kinases - genetics; Extracellular Signal-Regulated MAP Kinases - metabolism; Galactosamine - adverse effects; Gastrointestinal Microbiome; inducible nitric oxide synthase; inflammation; interleukin-1beta; intestinal microorganisms; JNK Mitogen-Activated Protein Kinases - genetics; JNK Mitogen-Activated Protein Kinases - metabolism; Lactobacillus casei; lipopolysaccharides; Lipopolysaccharides - adverse effects; liver; Liver - metabolism; Liver - microbiology; Liver Diseases - therapy; liver failure; Male; males; mitogen-activated protein kinase; myeloperoxidase; necrosis; nitric oxide; Nitric Oxide - blood; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Nutrition; Original Contribution; phosphorylation; PPAR gamma - genetics; PPAR gamma - metabolism; probiotics; Probiotics - administration & dosage; Rats; Rats, Wistar; Signal Transduction; Toll-like receptor 2; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Toll-like receptor 9; Toll-Like Receptor 9 - genetics; Toll-Like Receptor 9 - metabolism; tumor necrosis factor-alpha; Microbiota; Inflammation; TNF; PPAR-γ; Lactobacillus casei; TNF-α
• ISSN: 1436-6207; 1436-6215
• DOI: 10.1007/s00394-015-0904-3

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.