Journal of Xenobiotics

20 pages, 934 KB

Open AccessReview

Antioxidant Effect of Curcumin and Its Impact on Mitochondria: Evidence from Biological Models

by Karla Alejandra Avendaño-Briseño, Jorge Escutia-Martínez, Estefani Yaquelin Hernández-Cruz and José Pedraza-Chaverri

J. Xenobiot. 2025, 15(5), 139; https://doi.org/10.3390/jox15050139 - 31 Aug 2025

Abstract

Curcumin, the principal active component of turmeric, is a polyphenol that has been used in various countries for the treatment of numerous conditions due to its wide range of health benefits. Curcumin exhibits bifunctional antioxidant properties: the first is attributed to its chemical structure, which enables it to directly neutralize reactive oxygen species (ROS); the second is related to its ability to induce the expression of antioxidant enzymes via the transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2). Both ROS and Nrf2 are closely associated with mitochondrial function and metabolism, and their dysregulation may lead to mitochondrial dysfunction, potentially contributing to the development of various pathological conditions. Therefore, curcumin treatment appears highly promising and is strongly associated with the preservation of mitochondrial function. The aim of this review is to summarize the current literature on the impact of curcumin’s antioxidant properties on mitochondrial function. Specifically, studies conducted in different biological models are included, with emphasis on aspects such as mitochondrial respiration, antioxidant enzyme activity, interactions with mitochondrial membranes, and the role of curcumin in the regulation of intrinsic apoptosis. Full article

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17 pages, 2121 KB

Open AccessArticle

An Evolutionary Study in Glyphosate Oxidoreductase Gox Highlights Distinct Orthologous Groups and Novel Conserved Motifs That Can Classify Gox and Elucidate Its Biological Role

by Marina Giannakara, Vassiliki Lila Koumandou and Louis Papageorgiou

J. Xenobiot. 2025, 15(5), 138; https://doi.org/10.3390/jox15050138 - 29 Aug 2025

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Abstract

Glyphosate Oxidoreductase (Gox) is an enzyme known to degrade glyphosate, an intensively used wide-spectrum herbicide. Although it was first reported back in 1995, much remains unknown about its role in bacteria, its distribution across the bacterial kingdom, and its structure. This information would be valuable for better understanding the degradation pathway of glyphosate and for discovering new enzymes with the same potential. In the present study, a holistic evolutionary analysis has been performed towards identifying homologue proteins within the FAD-dependent/binding oxidoreductases family and extracting critical characteristics related to conserved protein domains and motifs that play a key role in this enzyme’s function. A total of 2220 representative protein sequences from 843 species and 10 classes of bacteria were analyzed, from which 4 protein domains, 2 characteristic/functional regions, and 8 conserved motifs were identified based on multiple sequence alignment and the annotated information from biological databases. The major goal of this study is the presentation of a novel phylogenetic tree for the Gox-related proteins to identify the major protein clusters and correlate them based on their sequence, structural, and functional information towards identifying new possible pharmacological targets that are related to this specific enzyme function. Considering the lack of information about Gox, the aim of this paper is to fill in these knowledge gaps, which can help determine the biological role of Gox and consequently better understand its function. Full article

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22 pages, 3119 KB

Open AccessArticle

Silica Nanoparticles Induced Epithelial–Mesenchymal Transition in BEAS-2B Cells via ER Stress and SIRT1/HSF1/HSPs Signaling Pathway

by Jinyan Pang, Liyan Xiao, Zhiqin Xiong, Kexin Zhang, Man Yang, Ji Wang, Yanbo Li and Yang Li

J. Xenobiot. 2025, 15(5), 137; https://doi.org/10.3390/jox15050137 - 23 Aug 2025

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Abstract

The extensive utilization of amorphous silica nanoparticles (SiNPs) has raised concerns regarding the potential health risks. Previous studies have indicated that SiNPs could trigger both the activation of heat shock proteins (HSPs) and epithelial–mesenchymal transition (EMT) in BEAS-2B cells; however, the underlying mechanisms require further elucidation. This study aimed to investigate how SiNPs activate the heat shock response (HSR) in BEAS-2B cells, which subsequently triggers EMT. Firstly, we observed that SiNPs were internalized by BEAS-2B cells and localized in the endoplasmic reticulum (ER), inducing ER stress. The ER stress led to the activation of SIRT1 by phosphorylation, which enhanced the nuclear transcriptional activity of HSF1 via deacetylation. HSF1 was found to upregulate the levels of HSP70 and HSP27 proteins, which further affected EMT-related genes and, ultimately, induced EMT. Additionally, 4-phenylbutyric acid (4-PBA) inhibited ER stress, which attenuated the SIRT1/HSF1 signaling pathway. The knockdown of SIRT1 and HSF1 using siRNA effectively suppressed the EMT progression. In summary, these results suggested that SiNPs activated the SIRT1/HSF1/HSPs pathway through ER stress, thereby triggering EMT in BEAS-2B cells. The present study identified a novel mechanism of SiNP-induced EMT, which has provided valuable insights for future toxicity studies and risk assessments of SiNPs. Full article

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21 pages, 420 KB

Open AccessArticle

Evaluation of Endocrine Disruptome and VirtualToxLab for Predicting Per- and Polyfluoroalkyl Substances Binding to Nuclear Receptors

by Nina Franko, Manca Vetrih and Marija Sollner Dolenc

J. Xenobiot. 2025, 15(5), 136; https://doi.org/10.3390/jox15050136 - 22 Aug 2025

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Abstract

This study investigated whether the Endocrine Disruptome and VirtualToxLab in silico platforms are suitable for predicting the endocrine disrupting effects of per- and polyfluoroalkyl substances (PFASs)—in particular, for interactions with oestrogen receptors (ERs) and androgen receptor (AR). Compounds included in the U.S. Environmental Protection Agency’s PFAS working list were analysed with both models, and the results were compared with the available in vitro data regarding their modulation of nuclear receptors. Based on the identified prediction parameters, such as sensitivity, specificity, accuracy, and Mathews’ correlation coefficient, VirtualToxLab was found to be a reliable model for predicting the reactivity of PFASs with AR, while a positive consensus approach of both platforms provided reliable predictions of the PFAS reactivity with ERα and ERβ. This study provides the evidence that Endocrine Disruptome and VirtualToxLab can be used as a tier 1 screening tool for assessment of the endocrine disrupting effect of PFASs. Furthermore, it demonstrates that the likelihood of endocrine disrupting properties increases with the lipophilicity of PFASs and identifies the understudied PFHpS, PFNS, PFDS, 9-Cl, NMeFOSAA, NEtFOSAA, 4:2 FTS, 6:2 FTS, 8:2 FTS, 6:2 monoPAP, 8:2 monoPAP, and 5:3 acid as potential ligands of AR and/or ERs. Full article

(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health: 2nd Edition)

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J. Xenobiot., Volume 15, Issue 5 (October 2025) – 4 articles

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