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Toxicology Research: Understanding and Predicting Compound—Induced Toxicity

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: 20 June 2026 | Viewed by 889

Special Issue Editors


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Guest Editor
School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Interests: animal models; organophosphates; acetylcholinesterase; neurochemistry; in vitro toxicology models; protein aggregation; cytotoxicity; skin diseases; nerve agents
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Pharmacy, School of Health Sciences, University of Patras, 26504 Rion-Patras, Greece
Interests: animal models; skin diseases; pharmaceutical/cosmeceutical testing; cytotoxicity; biocompatibility; in vitro models; a-synuclein; protein aggregation

Special Issue Information

Dear Colleagues,

This Special Issue in the International Journal of Molecular Sciences will cover a selection of recent research and review articles on “Toxicology Research: Understanding and Predicting Compound—Induced Toxicity”.

The prediction of compounds’ toxicity is important for drug development and in understanding the toxicity of various industrial and domestic chemicals. Multiple compounds are synthesized every year, and many new ones are entering the market, thus demanding the development of robust toxicology assessment platforms. For this, chemical threats should also be taken into consideration, and toxicological approaches are needed to understand their mechanisms of action and develop effective countermeasures.

Currently, there are multiple ways to assess the toxicity of a given or emerging chemical, including computational approaches, in vitro models, and in vivo studies. This Special Issue focuses on molecular toxicology; therefore, clinical studies, including biomolecular experiments that provide mechanistic insights into compound-induced toxicity, will be welcomed.

Suitable topics include but are not limited to the following:

  • Molecular toxicology;
  • Emerging toxicology;
  • Drug-induced toxicity;
  • Neurotoxicology;
  • Organ toxicology (kidney, lung, skin, etc.);
  • Animal models for toxicity studies;
  • In vitro models for toxicity assessment;
  • Pesticides;
  • Industrial chemicals;
  • Nerve agents;
  • In silico toxicology;
  • QSAR and SAR studies.

Dr. Georgios Pampalakis
Dr. Eleni Zingkou
Guest Editors

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 submissions that pass pre-check are 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 250 words) can be sent to the Editorial Office for assessment.

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 single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • molecular toxicology
  • emerging toxicology
  • drug-induced toxicity
  • organ toxicology
  • animal models
  • in silico toxicology
  • in vitro models
  • pesticides
  • industrial chemicals

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Published Papers (1 paper)

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18 pages, 5094 KB  
Article
Effects of Ritonavir, Lopinavir, and Alcohol on ABC Transporters and Secretion of Bile Acid and Bilirubin in Senescent Hepatocytes
by Liting Chen, Eric Duran, Diego Headrick and Cheng Ji
Int. J. Mol. Sci. 2026, 27(3), 1189; https://doi.org/10.3390/ijms27031189 - 25 Jan 2026
Viewed by 526
Abstract
Drug- and alcohol-induced liver injury involves impaired bile acids or bilirubin secretion, but it is not known how senescence influences the secretion of hepatocytes exposed to drugs and alcohol. In this study, the toxic effects of ritonavir, lopinavir, and alcohol on hepatocyte transporters [...] Read more.
Drug- and alcohol-induced liver injury involves impaired bile acids or bilirubin secretion, but it is not known how senescence influences the secretion of hepatocytes exposed to drugs and alcohol. In this study, the toxic effects of ritonavir, lopinavir, and alcohol on hepatocyte transporters and the secretion of bile acids and bilirubin were investigated in hydrogen peroxide-induced senescent HepG2 and doxorubicin-induced senescent primary human hepatocytes. In HepG2, intracellular conjugated bilirubin increased upon senescence and extracellular conjugated bilirubin in culture medium was decreased by ritonavir and lopinavir treatment. In the primary hepatocytes, intracellular bile acids or medium bilirubin were not significantly changed upon senescence. However, intracellular bile acids were increased, and medium conjugated bilirubin were decreased in senescent primary hepatocytes treated with alcohol and the two drugs. Transcriptional expressions of adenosine triphosphate (ATP)-binding cassette (ABC) transporters (ABCB4, ABCC6, ABCB11, and ABCD3) were decreased whereas UDP-glucuronosyltransferase (UGT1A1) was increased by ritonavir and lopinavir in senescent HepG2. In senescent primary hepatocytes, expressions of ABCB11, ABCC1, ABCC2, ABCC3, ABCC4, and ABCC6 were apparently reduced whereas UGT1A1 and the cytochrome P450 enzyme CYP7A1 were markedly increased by alcohol combined with ritonavir and lopinavir. Selective ABCC6 knockdown in the primary hepatocytes altered expressions of two senescence markers, Lamin A/C and cyclin-dependent kinase inhibitor CKI (p21), increased expressions of CYP7A1 and hydroxy methyl glutaryl-CoA reductase (HMGCR), and increased intracellular bile acids. Further, anti-cholestasis agents, ursodeoxycholic acid and glycyrrhizin, significantly ameliorated the impaired secretions of bile acids and bilirubin as well as reducing intracellular lipid accumulation and cell death caused by ritonavir, lopinavir, and alcohol in the primary hepatocytes with ABCC6 knockdown. These results indicate that senescence moderately impairs the ABC transporters of hepatocytes and secretion of bile acids or bilirubin, which become worse in the presence of the drugs and alcohol but could be improved by anti-cholestasis agents. Full article
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