The Thermostable Direct Hemolysin from Grimontia hollisae Causes Acute Hepatotoxicity In Vitro and In Vivo
Journal
PLoS ONE
Journal Volume
8
Journal Issue
2
Pages
e56226
Date Issued
2013
Author(s)
Lin, Yan-Ren; Chen, Yao-Li; Wang, Keh-Bin; Wu, Yi-Fang; Wang, Yu-Kuo; Huang, Sheng-Cih; Liu, Tzu-An; Nayak, Manoswini; Wu, Tung-Kung
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. ? 2013 Lin et al.
SDGs
Other Subjects
aminotransferase; fluorescein isothiocyanate; hemolysin; animal cell; animal experiment; animal model; article; cell structure; cellular distribution; computer assisted emission tomography; controlled study; cytotoxicity test; female; Gram negative facultatively anaerobic rods; Grimontia hollisae; human; human cell; in vitro study; in vivo study; liver biopsy; liver function; liver metabolism; liver toxicity; mouse; nonhuman; protein localization; Amino Acid Sequence; Animals; Bacterial Toxins; Cardiovascular Diseases; Fluorescein-5-isothiocyanate; Fluorodeoxyglucose F18; Hemolysin Proteins; Hemolysis; Humans; Kidney Diseases; Liver; Liver Diseases; Liver Function Tests; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Positron-Emission Tomography; Protein Transport; Recombinant Proteins; Subcellular Fractions; Vibrionaceae
Type
journal article