title: The thermostable direct hemolysin from Grimontia hollisae causes acute hepatotoxicity in vitro and in vivo.
abstract: BACKGROUND
  G. hollisae thermostable direct hemolysin (Gh-TDH) is produced by most strains of G. hollisae. This toxin has been reported to be absorbed in the intestines in humans. Secondary liver injury might be caused by venous return of the toxin through the portal system. We aimed to firstly analyze the in vitro and in vivo hepatotoxicity of Gh-TDH.
  
  
  METHODS
  Liver cells (primary human non-cancer cell and FL83B mouse cells) were treated and mice (BALB/c) were fed with this toxin to investigate its hepatotoxicity. Morphological examination and cytotoxicity assays using liver cells were also performed. Fluorescein isothiocyanate-conjugated toxin was used to analyze the localization of this protein in liver cells. Mice were subjected to liver function measurements and liver biopsies following toxin treatment and wild-type bacterial infection. PET (positron emission tomography)/CT (computed tomography) images were taken to assess liver metabolism during acute injury and recovery.
  
  
  RESULTS
  The effect of hepatotoxicity was dose and time dependent. Cellular localization showed that the toxin was initially located around the cellular margins and subsequently entered the nucleus. Liver function measurements and liver biopsies of the mice following treatment with toxin or infection with wild-type Grimontia hollisae showed elevated levels of transaminases and damage to the periportal area, respectively. The PET/CT images revealed that the reconstruction of the liver continued for at least one week after exposure to a single dose of the toxin or bacterial infection.
  
  
  CONCLUSIONS
  The hepatotoxicity of Gh-TDH was firstly demonstrated. The damage was located in the periportal area of the liver, and the liver became functionally insufficient.
authors: Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan, Republic of China.
authors: Yan-Ren
authors: YR
authors: Lin
authors: Yao-Li
authors: YL
authors: Chen
authors: Keh-Bin
authors: KB
authors: Wang
authors: Yi-Fang
authors: YF
authors: Wu
authors: Yu-Kuo
authors: YK
authors: Wang
authors: Sheng-Cih
authors: SC
authors: Huang
authors: Tzu-An
authors: TA
authors: Liu
authors: Manoswini
authors: M
authors: Nayak
authors: Bak-Sau
authors: BS
authors: Yip
authors: Tung-Kung
authors: TK
authors: Wu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D002318:Cardiovascular Diseases / Q000382:microbiology / Q000473:pathology; D016650:Fluorescein-5-isothiocyanate; D019788:Fluorodeoxyglucose F18; D006460:Hemolysin Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000382:microbiology / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008107:Liver Diseases / Q000000981:diagnostic imaging / Q000382:microbiology* / Q000473:pathology* / Q000503:physiopathology; D008111:Liver Function Tests; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D049268:Positron-Emission Tomography; D021381:Protein Transport / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014737:Vibrionaceae / Q000737:chemistry*
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D011994:Recombinant Proteins; D019788:Fluorodeoxyglucose F18; C068489:thermostable direct hemolysin; D016650:Fluorescein-5-isothiocyanate