title: Probiotic Lactobacillus casei Zhang reduces pro-inflammatory cytokine production and hepatic inflammation in a rat model of acute liver failure.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmaceutical Engineering, College of Life Science, Inner Mongolia Agricultural University, No. 306 Zhaowuda Road, Saihan district, Hohhot, 010018, People's Republic of China. wangyuzhen817@126.com.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Clinical Laboratory, Inner Mongolia People's Hospital, Hohhot, People's Republic of China.
authors.forename: Jiming
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Pharmaceutical Engineering, College of Life Science, Inner Mongolia Agricultural University, No. 306 Zhaowuda Road, Saihan district, Hohhot, 010018, People's Republic of China.
authors.forename: Yunxu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Engineering, College of Life Science, Inner Mongolia Agricultural University, No. 306 Zhaowuda Road, Saihan district, Hohhot, 010018, People's Republic of China.
authors.forename: Shichao
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Pharmaceutical Engineering, College of Life Science, Inner Mongolia Agricultural University, No. 306 Zhaowuda Road, Saihan district, Hohhot, 010018, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Engineering, College of Life Science, Inner Mongolia Agricultural University, No. 306 Zhaowuda Road, Saihan district, Hohhot, 010018, People's Republic of China.
authors.forename: Junna
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Engineering, College of Life Science, Inner Mongolia Agricultural University, No. 306 Zhaowuda Road, Saihan district, Hohhot, 010018, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Engineering, College of Life Science, Inner Mongolia Agricultural University, No. 306 Zhaowuda Road, Saihan district, Hohhot, 010018, People's Republic of China.
authors.forename: Shimin
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Dairy Biotechnology and Bioengineering, Educational Ministry of China, College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Dairy Biotechnology and Bioengineering, Educational Ministry of China, College of Food Science and Engineering, Inner Mongolia Agricultural University, Hohhot, People's Republic of China.
authors.forename: Heping
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001644:Bifidobacterium; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005688:Galactosamine / Q000009:adverse effects; D000069196:Gastrointestinal Microbiome; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D007780:Lacticaseibacillus casei; D008070:Lipopolysaccharides / Q000009:adverse effects; D008099:Liver / Q000378:metabolism / Q000382:microbiology*; D008107:Liver Diseases / Q000628:therapy*; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D019936:Probiotics / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D047495:PPAR gamma; C495343:Tlr2 protein, rat; C489640:Tlr9 protein, rat; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9; D009569:Nitric Oxide; D005688:Galactosamine; D003907:Dexamethasone; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Inflammation; Lactobacillus casei; Microbiota; PPAR-γ; TNF-α