Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
6.4
4.1
Journals
Toxics
Special Issues
Drug Metabolism and Toxicological Mechanisms—2nd Edition
share announcement

Drug Metabolism and Toxicological Mechanisms—2nd Edition

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Drugs Toxicity".

Deadline for manuscript submissions: closed (10 April 2026) | Viewed by 6619

Special Issue Editors

Prof. Dr. Qi Wang

E-Mail Website
Guest Editor
Department of Toxicology, School of Public Health, Peking University, Beijing, China
Interests: cellular and computational toxicology
Special Issues, Collections and Topics in MDPI journals
Dr. Youbo Zhang

E-Mail Website
Guest Editor
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Interests: natural products analysis; pharmacological research; nuclear receptor function; metabolic diseases
Special Issues, Collections and Topics in MDPI journals
Dr. An Zhu

E-Mail Website
Guest Editor
Key Laboratory of Gastrointestinal Cancer, Fujian Medical University, Ministry of Education, Fuzhou 350108, China
Interests: drug toxicology; computational toxicology; epitranscriptomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Absorption, distribution, metabolism, and excretion (ADME) processes are of great importance in understanding how the body disposes and responds to drugs. These processes play a pivotal role in assessing the efficacy and safety of drugs, while also enabling the prediction of potential adverse reactions or toxicities. A parent drug can undergo biotransformation induced by drug-metabolizing enzymes, leading to the formation of either toxic metabolites (metabolic activation) or non-toxic metabolites (detoxification). Thus, drug metabolism can be a key determinant of drug toxicity. Recently, new approach methodologies such as in silico methods, based on non-animal data, have been developed and applied in regulatory practices.

The first edition of the Special Issue on “Drug Metabolism and Toxicological Mechanisms” featured original research articles and comprehensive reviews that highlighted innovative methods and models. These included advancements in computational toxicology, the use of zebrafish as a model organism, and the application of multi-omics high-throughput sequencing technologies. These approaches were explored for their potential in enhancing toxicological risk assessment during the ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) processes of drug development. This Special Issue mainly focuses on drug metabolism and toxicological mechanisms. It extensively covers a range of topics, including drug metabolism, physiologically based pharmacokinetic (PBPK) modeling, toxicokinetics–toxicodynamics (TK–TD), ADME characterization, the identification and toxicity of metabolites, high-throughput pharmacokinetics (HT-PK), organ-specific toxicity, and toxicological mechanisms.

Prof. Dr. Qi Wang
Dr. Youbo Zhang
Dr. An Zhu
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. Toxics 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 2600 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

  • drug metabolism
  • toxicity
  • mechanism
  • preclinical study
  • clinical trial

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Related Special Issue

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

19 pages, 2932 KB  
Article
Plasma Concentrations of Endotoxin Lipopolysaccharide and High-Mobility Group Box 1 Protein Are Consistent Sex-Specific Biomarkers of Alcohol Abstinence Associated with Alcohol Use Disorder
by Isaac Hurtado-Guerrero, Nuria García-Marchena, Jaime Martín-Martín, María Flores-López, Nerea Requena-Ocaña, María del Mar Fernández-Arjona, Antonio J. López-Gambero, Patricia Rivera, Leticia Rubio, Gabriel Rubio, Antonia Serrano, Fernando Rodríguez de Fonseca and Juan Suarez
Toxics 2026, 14(5), 440; https://doi.org/10.3390/toxics14050440 - 15 May 2026
Viewed by 392
Abstract
Alcohol use disorder (AUD) is associated with gut dysbiosis through interactions with the immune system. The present study aimed to investigate whether endotoxin lipopolysaccharides (LPS) and high-mobility group box-1 protein (HMGB1), a key inflammatory mediator, as well as the metabolic fat mass hormone [...] Read more.
Alcohol use disorder (AUD) is associated with gut dysbiosis through interactions with the immune system. The present study aimed to investigate whether endotoxin lipopolysaccharides (LPS) and high-mobility group box-1 protein (HMGB1), a key inflammatory mediator, as well as the metabolic fat mass hormone leptin, are reliable biomarkers for the estimation of alcohol dependence and abstinence. AUD outpatients (N = 122) and healthy volunteers (N = 63) were recruited and assessed by using the Psychiatric Research Interview for Substance and Mental Disorders according to DSM-IV-TR after blood extraction. The results indicated that AUD patients had higher plasma concentrations of LPS and HMGB1, and lower plasma concentrations of leptin and SDF-1α compared to healthy subjects. Two logistic models, including HMGB1, leptin and SDF-1α (model 1) or LPS (model 2), provided high discriminatory powers to identify AUD patients [prognostic probability: model 1 = 0.90 (0.78); model 2 = 0.86 (0.79); p < 0.001]. LPS and HMGB1 positively correlated with alcohol abstinence duration in male AUD patients only. Linear logistic regression included LPS, HMGB1, fractalkine, SDF-1α and/or leptin to accurately estimate the duration of problematic alcohol use and alcohol abstinence when sexes were analyzed separately. These results suggest that LPS and HMGB1 are relevant sex-specific actors for predicting alcohol abstinence and problematic alcohol use in AUD patients. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms—2nd Edition)
►▼ Show Figures

Graphical abstract

22 pages, 5076 KB  
Article
Reprogramming of the m6A Epitranscriptome Drives Triptolide-Induced Reproductive Toxicity in HTR-8/SVneo Cells
by Xinru Liu, Yunli Wu, Jin Tian, Jiaxin Wen, Yuan Shi, Lili Wang, An Zhu and Zekai Wu
Toxics 2026, 14(4), 334; https://doi.org/10.3390/toxics14040334 - 16 Apr 2026
Viewed by 435
Abstract
Triptolide (TPL), the core active component of the traditional Chinese medicinal herb Tripterygium wilfordii Hook F (TwHF), possesses a wide spectrum of pharmacological activities, including anti-inflammatory, neuroprotective, immunosuppressive, and anti-tumor activities. However, its clinical application is severely limited by significant reproductive toxicity, the [...] Read more.
Triptolide (TPL), the core active component of the traditional Chinese medicinal herb Tripterygium wilfordii Hook F (TwHF), possesses a wide spectrum of pharmacological activities, including anti-inflammatory, neuroprotective, immunosuppressive, and anti-tumor activities. However, its clinical application is severely limited by significant reproductive toxicity, the mechanism of which remains poorly understood. Using an integrated analysis of MeRIP-seq and mRNA-seq data, coupled with experimental validation in HTR-8/SVneo cells, we systematically elucidated the molecular mechanism by which TPL induces trophoblast cell injury. Our findings revealed that TPL significantly altered intracellular N6-methyladenosine (m6A) modification and gene expression profiles, with 1774 genes displaying hypomethylation concurrent with mRNA upregulation. According to the functional enrichment analysis, these genes showed significant enrichment in several key pathways associated with reproduction, including autophagy, DNA damage response, mitochondrial outer membrane, and positive regulation of apoptotic process. Molecular docking further demonstrated direct and stable binding of TPL to key m6A regulators, leading to specific demethylation of targets including E2F1 and PPP1CC. This study uncovers a novel post-transcriptional mechanism where TPL disrupts m6A modification, thereby perturbing essential trophoblast functions and driving reproductive toxicity. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms—2nd Edition)
►▼ Show Figures

Graphical abstract

19 pages, 2138 KB  
Article
Metabolic Profiling and Detoxification of Eupalinolide A and B in Human Liver Microsomal Systems
by Yingzi Li, Xiaoyan Liu, Ludi Li, Wusheng Xiao, Youbo Zhang, Kewu Zeng and Qi Wang
Toxics 2026, 14(3), 235; https://doi.org/10.3390/toxics14030235 - 9 Mar 2026
Viewed by 647
Abstract
Eupalinolide A (EA, Z-configuration) and Eupalinolide B (EB, E-configuration) are cis-trans isomeric sesquiterpenoid monomers isolated from Eupatorium lindleyanum DC. (Asteraceae). Although these compounds display anti-inflammatory and anti-tumor activities, their metabolite profiles and possible hepatotoxicity remain largely unknown. This study aimed to [...] Read more.
Eupalinolide A (EA, Z-configuration) and Eupalinolide B (EB, E-configuration) are cis-trans isomeric sesquiterpenoid monomers isolated from Eupatorium lindleyanum DC. (Asteraceae). Although these compounds display anti-inflammatory and anti-tumor activities, their metabolite profiles and possible hepatotoxicity remain largely unknown. This study aimed to investigate the metabolic profiles of EA and EB in liver microsomes and clarify whether they undergo metabolic activation or detoxification. EA and EB were metabolically profiled in human liver microsomes (HLMs) via UPLC-Q-TOF-MS. A HepG2-HLM co-culture system was used to compare the hepatocyte toxicity of parent compounds and their hydrolysis, oxidation, and hydrolysis–oxidation metabolites, thus evaluating their metabolic detoxification pathways. Sixteen metabolites of EA and 19 of EB were identified, with hydrolysis being the predominant metabolic pathway for both isomers. Both compounds showed low hepatocyte toxicity and underwent metabolic detoxification mainly via hydrolytic and oxidative pathways. Notably, hydrolysis metabolites had significantly lower toxicity than oxidative products in HepG2 cells. These results suggest that EA and EB could present a relatively low risk of in vivo hepatotoxicity, which provides useful information for understanding the metabolic behavior and safety profile of these bioactive sesquiterpenoids. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms—2nd Edition)
►▼ Show Figures

Graphical abstract

16 pages, 1764 KB  
Article
Insights into Transport Function of the Murine Organic Anion-Transporting Polypeptide OATP1B2 by Comparison with Its Rat and Human Orthologues
by Saskia Floerl, Annett Kuehne and Yohannes Hagos
Toxics 2026, 14(1), 10; https://doi.org/10.3390/toxics14010010 - 20 Dec 2025
Viewed by 851
Abstract
Organic anion-transporting polypeptides (OATPs) are key transporters of hepatic uptake for endogenous compounds and xenobiotics. Human OATP1B1 and OATP1B3 are well-studied due to their role in drug–drug interactions. In contrast, data on murine OATP1B2, the rodent orthologue of these transporters, are limited, despite [...] Read more.
Organic anion-transporting polypeptides (OATPs) are key transporters of hepatic uptake for endogenous compounds and xenobiotics. Human OATP1B1 and OATP1B3 are well-studied due to their role in drug–drug interactions. In contrast, data on murine OATP1B2, the rodent orthologue of these transporters, are limited, despite its importance in early drug development. Here, we systematically compared the transport characteristics of mouse and rat OATP1B2 under identical experimental conditions. The Km values for estrone-3-sulfate (E1S) and taurocholate (TCA) were 242 and 73 µM for mOATP1B2 and 90 and 16 µM for rOATP1B2. Nine clinically relevant drugs were evaluated for inhibitory effects, showing strong correlation between species. Cyclosporine A, ritonavir, odevixibat, rosuvastatin, and rifampicin markedly inhibited uptake. Rifampicin demonstrated species-specific differences, with higher IC50 values for mOATP1B2 (E1S: 9.6 µM; TCA: 7.7 µM) than rOATP1B2 (E1S: 1.1 µM; TCA: 2.4 µM). A comparison of the rodent data with the human orthologues revealed similar inhibition patterns but distinct substrate selectivity: hOATP1B1 showed high affinity for E1S but negligible TCA uptake, while hOATP1B3 transported TCA weakly but not E1S. This study provides insights into species-specific differences in OATP-mediated hepatic uptake and is therefore valuable for the interpretation of preclinical studies and their transfer to human pharmacology. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms—2nd Edition)
►▼ Show Figures

Graphical abstract

13 pages, 736 KB  
Article
From Euphoria to Cardiac Stress: Role of Oxidative Stress on the Cardiotoxicity of Methylone and 3,4-DMMC
by Maria Moreira, Verónica Rocha, Ana Margarida Araújo and Márcia Carvalho
Toxics 2025, 13(11), 998; https://doi.org/10.3390/toxics13110998 - 20 Nov 2025
Viewed by 2723
Abstract
Synthetic cathinones (SCs), commonly referred to as “bath salts”, are a class of novel psychoactive substances (NPSs) that elicit amphetamine-like effects and severe cardiovascular outcomes, including myocardial infarction and sudden cardiac death. Despite these risks, the mechanisms underlying SC-induced cardiotoxicity remain poorly studied. [...] Read more.
Synthetic cathinones (SCs), commonly referred to as “bath salts”, are a class of novel psychoactive substances (NPSs) that elicit amphetamine-like effects and severe cardiovascular outcomes, including myocardial infarction and sudden cardiac death. Despite these risks, the mechanisms underlying SC-induced cardiotoxicity remain poorly studied. This study investigated the in vitro cardiotoxicity of two prevalent SCs—methylone and 3,4-dimethylmethcathinone (3,4-DMMC)—in H9c2 rat cardiomyoblasts, focusing on oxidative stress and the potential protective role of antioxidants. Cells were exposed to methylone (0.01–4.0 mM) or 3,4-DMMC (0.0005–0.8 mM) for 24 and 48 h, and cytotoxicity was assessed by an MTT assay. Intracellular reactive oxygen/nitrogen species (ROS/RNS) were quantified by fluorescence, and antioxidant effects were evaluated using ascorbic acid, N-acetylcysteine, and Trolox. Both SCs caused concentration-dependent cytotoxicity, with 3,4-DMMC showing higher potency than methylone (IC50: 0.28 vs. 0.98 mM, p = 0.0013). ROS/RNS levels increased in a concentration- and time-dependent manner for both compounds, reflecting early and sustained redox imbalance. Of the antioxidants, only ascorbic acid significantly improved cell viability. Taken together, these findings demonstrate for the first time that methylone and 3,4-DMMC exert cardiotoxic effects in vitro, with oxidative stress as a key contributor. The protective effect of ascorbic acid highlights its potential as a therapeutic candidate against SC-induced cardiac injury. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms—2nd Edition)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

26 pages, 1092 KB  
Review
ABCG2 Genetic Variability in Drug Exposure and Toxicity: Implications for Clinical Practice
by Tamara Božina, Livija Šimičević, Lana Ganoci, Mila Lovrić, Iva Klarica Domjanović, Vladimir Trkulja and Nada Božina
Toxics 2026, 14(4), 327; https://doi.org/10.3390/toxics14040327 - 15 Apr 2026
Viewed by 697
Abstract
The ATP-binding cassette subfamily G member 2 (ABCG2), also known as breast cancer resistance protein (BCRP), is an efflux transporter expressed in key pharmacokinetic tissues and biological barriers. It regulates exposure to many endogenous compounds, drugs, and environmental toxins. Genetic variability in ABCG2 [...] Read more.
The ATP-binding cassette subfamily G member 2 (ABCG2), also known as breast cancer resistance protein (BCRP), is an efflux transporter expressed in key pharmacokinetic tissues and biological barriers. It regulates exposure to many endogenous compounds, drugs, and environmental toxins. Genetic variability in ABCG2 has been recognised as an important contributor to interindividual variability in drug response, especially in terms of efficacy and toxicity. This narrative review summarises current knowledge on the clinical relevance of ABCG2 genetic variants, with a focus on their effects on pharmacokinetics, adverse drug reactions and drug–drug–gene interactions, as well as their potential implementation in personalised therapy. A literature search was performed in PubMed, Scopus and the Clinical Pharmacogenomics Database (ClinPGx), with an emphasis on clinically relevant studies and available pharmacogenomic guidelines. The most investigated ABCG2 variant, c.421C>A (rs2231142; p.Gln141Lys), is consistently associated with reduced transporter activity and increased systemic exposure to several substrate drugs, including statins, allopurinol and anticancer agents, which may influence both treatment response and the risk of toxicity. Although growing evidence supports the clinical relevance of ABCG2 genotyping, its routine implementation remains limited. Integration of ABCG2 variability into polygenic models and clinical decision-support tools may further improve individualised treatment, particularly in patients with multimorbidity and polypharmacy. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms—2nd Edition)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop