Special Issue "Hepatotoxin Exposures, Molecular Mechanisms, and Implications for Liver Diseases"

A special issue of Toxins (ISSN 2072-6651).

Deadline for manuscript submissions: 31 July 2021.

Special Issue Editor

Dr. John Clarke
E-Mail Website
Guest Editor
Washington State University, WA, USA

Special Issue Information

Dear Colleagues,

The liver is a major detoxification organ and encounters toxins from many different sources, including but not limited to endotoxins, exotoxins, mycotoxins, and phycotoxins. These hepatotoxins can initiate and propagate various liver diseases through molecular and cellular mechanisms of liver damage (e.g., apoptosis, necrosis, inflammation, steatosis) and repair (e.g., proliferation, collagen deposition, regeneration). These mechanisms are mediated through cell-type specific effects in hepatocytes, stellate cells, Kupffer cells, endothelial cells, and cholangiocytes. Many liver diseases develop over a long period of time and have multifaceted etiology, providing a continual opportunity for toxins to influence disease progression. There is a great need to better understand fundamental pathogenic toxin mechanisms in various species to connect exposures (intermittent or continual) to liver diseases and improve risk assessment for different toxins.

This Special Issue welcomes submissions that span the research spectrum from preclinical to clinical. These include but are not limited to:

  • Hepatotoxin exposure assessment in model organisms or human populations;
  • Fundamental mechanisms of hepatotoxin in liver damage in in vitro systems or model organisms;
  • Roles of hepatotoxin in liver disease etiology and/or progression;
  • Interaction between hepatotoxins and other liver disease risk factors;
  • Review articles addressing the established, putative, and unexplored connections between toxins and liver diseases.

Dr. John Clarke
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • exposures
  • hepatoxicity
  • alcoholic liver disease
  • hepatocellular carcinoma
  • fatty liver disease
  • preclinical models
  • clinical evidence

Published Papers (3 papers)

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Research

Open AccessArticle
Identification of Decrease in TRiC Proteins as Novel Targets of Alpha-Amanitin-Derived Hepatotoxicity by Comparative Proteomic Analysis In Vitro
Toxins 2021, 13(3), 197; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13030197 - 09 Mar 2021
Viewed by 377
Abstract
Alpha-amanitin (α-AMA) is a cyclic peptide and one of the most lethal mushroom amatoxins found in Amanita phalloides. α-AMA is known to cause hepatotoxicity through RNA polymerase II inhibition, which acts in RNA and DNA translocation. To investigate the toxic signature of [...] Read more.
Alpha-amanitin (α-AMA) is a cyclic peptide and one of the most lethal mushroom amatoxins found in Amanita phalloides. α-AMA is known to cause hepatotoxicity through RNA polymerase II inhibition, which acts in RNA and DNA translocation. To investigate the toxic signature of α-AMA beyond known mechanisms, we used quantitative nanoflow liquid chromatography–tandem mass spectrometry analysis coupled with tandem mass tag labeling to examine proteome dynamics in Huh-7 human hepatoma cells treated with toxic concentrations of α-AMA. Among the 1828 proteins identified, we quantified 1563 proteins, which revealed that four subunits in the T-complex protein 1-ring complex protein decreased depending on the α-AMA concentration. We conducted bioinformatics analyses of the quantified proteins to characterize the toxic signature of α-AMA in hepatoma cells. This is the first report of global changes in proteome abundance with variations in α-AMA concentration, and our findings suggest a novel molecular regulation mechanism for hepatotoxicity. Full article
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Open AccessCommunication
Fungi–Bacteria Correlation in Alcoholic Hepatitis Patients
Toxins 2021, 13(2), 143; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020143 - 14 Feb 2021
Viewed by 530
Abstract
Alcohol-related liver disease is one of the most prevalent types of chronic liver diseases globally. Alcohol-related liver disease begins with fatty liver, which further develops into hepatic inflammation, hepatocyte injury, and progresses to fibrosis and cirrhosis. Compositional changes of gut bacteria and fungi [...] Read more.
Alcohol-related liver disease is one of the most prevalent types of chronic liver diseases globally. Alcohol-related liver disease begins with fatty liver, which further develops into hepatic inflammation, hepatocyte injury, and progresses to fibrosis and cirrhosis. Compositional changes of gut bacteria and fungi were found in patients with alcohol-related liver disease. However, the functional changes of fungi and correlations between fungi and bacteria have not been investigated. In this study, we first examined the functional capacity of fungi in patients with alcohol-related liver disease using shotgun metagenomics. Among 24 MetaCyc pathways contributed by fungi, superpathway of allantoin degradation in yeast was enriched in patients with alcoholic hepatitis. Furthermore, we compared the predictive power of bacteria versus fungi and found that bacteria performed better than fungi to separate patients with alcoholic hepatitis from non-alcoholic controls and patients with alcohol use disorder. Finally, we investigated the associations between the intestinal fungi and bacteria in alcoholic hepatitis patients. Positive association between fungi and bacteria was found between Cladosporium and Gemmiger, meanwhile negative association was found between Cryptococcus and Pseudomonas in alcoholic hepatitis patients. Full article
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Open AccessArticle
Effects of Cassava Juice (Manihot esculenta Crantz) on Renal and Hepatic Function and Motor Impairments in Male Rats
Toxins 2020, 12(11), 708; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12110708 - 09 Nov 2020
Viewed by 591
Abstract
Cassava (Manihot esculenta Crantz) is a plant that contains neurotoxins such as linamarin and lotaustraline. Its long-term consumption is associated with neuronal damage and contributes to the development of motor impairment in humans and rats. We investigated the effects of the consumption [...] Read more.
Cassava (Manihot esculenta Crantz) is a plant that contains neurotoxins such as linamarin and lotaustraline. Its long-term consumption is associated with neuronal damage and contributes to the development of motor impairment in humans and rats. We investigated the effects of the consumption of cassava juice on renal and hepatic function and motor impairments in male rats. The rats received the vehicle, non-toxic and toxic doses of cassava juice, or linamarin as a pharmacological control, over 35 consecutive days. The effects were evaluated in an open field test, rotarod, and swim test. The toxic cassava dose and linamarin resulted in motor impairments in the rotarod and swim test from day 7 of treatment. The toxic cassava dose and linamarin increased the parameters that indicate renal and hepatic damage, with the exception of total protein and albumin levels. Behavioral variables that show motor incoordination (i.e., latency to fall in the rotarod) were negatively correlated with biochemical parameters of renal and kidney damage, whereas spin behavior was positively correlated. Our data indicate that chronic oral consumption of cassava juice caused renal and hepatic damage that was correlated with motor coordination impairment in rats, similarly to their principal neurotoxic compound, linamarin. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: cyanotoxin liver effects and connections to liver diseases
Authors: John Clarke
Affiliation: Washington State University, WA, USA

Title: Effects of CDCA on T-2 Toxin and Deoxynivalenol Blood Concentration and Alleviation Toxicity in Broilers
Authors: Lisheng zhang
Affiliation: School of Veterinary Medicine, Huazhong Agricultural University 1st Shizishan Street, Hongshan, Wuhan 430070 China

Title: Potential contribution of renal and liver damage to motor impairments associated with neurotoxic metabolites of cassava (Manihot esculenta Crantz) in rats
Authors: Eduardo Rivadeneyra-Domínguez; José Eduardo Pérez- Pérez; Alma Vázquez- Luna; Rafael Diaz-Sobac; Juan Francisco Rodríguez- Landa
Affiliation: Facultad de Química Farmacéutica Biológica, Universidad Veracruzana, Xalapa, Veracruz, México
Abstract: Cassava (Manihot esculenta Crantz) is a food that contains such neurotoxins as linamarin and lotaustraline. Its long-term consumption is associated with neuronal damage in the brain and contributes to the development of tropical ataxic neuropathy, Konzo, and motor impairments in experimental animals. The present study investigated the effects of the consumption of cassava juice on renal and hepatic function and motor impairments in male Wistar rats. The rats received water, a non-toxic dose of cassava juice, a toxic dose of cassava juice, or linamarin as a pharmacological control. Neurotoxicity was then evaluated for 35 consecutive days. Spontaneous motor activity was evaluated in the open field test, rotarod test, and swim test. The groups that were treated with a toxic cassava dose and linamarin developed motor impairments in the rotarod test and swim test beginning on day 7. Parameters that integrate renal and hepatic function increased, with the exception of total protein and albumin levels, with the toxic cassava dose group and linamarin group compared with the control and non-toxic cassava dose groups. The chronic oral administration of cassava juice caused renal and hepatic damage, the metabolic products of which could negatively impact the central nervous system.

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