Aims: Anethole dithiolethione (ADT) is a marketed drug to treat xerostomia. Its mechanism of action is still unknown, but several preclinical studies indicate that it is able to increase intracellular glutathione (GSH) and protect against oxidative stress. Here, we investigated the molecular mechanisms behind these effects.
Results: Oral treatment of rats confirmed the GSH enhancing properties of ADT; among the different organs examined in this study, only the kidney showed a significant GSH increase that was already observed at low-dose treatments. The increase in GSH correlated with a decrease in -glutamyltranspeptidase (-GT) activity of the different tissues. and experiments with tubular renal cells and isolated perfused rat kidney showed that the cellular uptake of intact GSH was correlated with the extracellular concentrations of GSH.
Conclusion: s. The prominent pharmacological effect of ADT was a marked increase of GSH concentration in the kidney and a decrease of some systemic and renal biomarkers of oxidative stress. In particular, by inhibition of -GT activity, it decreased the production cysteinylglycine, a thiol that has prooxidant effects as the consequence of its autooxidation. The activity of ADT as GSH enhancer in both the circulation and the kidney was long-lasting. All these characteristics make ADT a promising drug to protect the kidney, and in particular proximal tubule cells, from xenobiotic-induced damage.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539083 | PMC |
| http://dx.doi.org/10.1155/2020/3562972 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Manganese Porphyrin-Containing Polymeric Micelles: A Novel Approach for Intracellular Catalytic Formation of Per/Polysulfide Species from a Hydrogen Sulfide Donor.
Adv Healthc Mater
February 2024
Department of Materials Science and Engineering, The Pennsylvania State University, Steidle Building, University Park, PA, 1680, USA.
Per/polysulfide species that are generated from endogenously produced hydrogen sulfide have critical regulatory roles in a wide range of cellular processes. However, the lack of delivery systems that enable controlled and sustained release of these unstable species in biological systems hinders the advancement of sulfide biology research, as well as the translation of knowledge to therapeutic applications. Here, a novel approach is developed to generate per/polysulfide species in cells by combining an H S donor and manganese porphyrin-containing polymeric micelles (MnPMCs) that catalyze oxidization of H S to per/polysulfide species.
View Article and Find Full Text PDFReactive Oxygen Species-Triggered Hydrogen Sulfide Release and Cancer-Selective Antiproliferative Effect of Anethole Dithiolethione-Containing Polymeric Micelles.
Adv Healthc Mater
January 2023
Department of Materials Science and Engineering, The Pennsylvania State University, University Park, PA, 16802, USA.
Hydrogen sulfide (H S) is a gaseous signaling molecule in the human body and has attracted attention in cancer therapy due to its regulatory roles in cancer cell proliferation and migration. Accumulating evidence suggests that continuous delivery of H S to cancer cells for extended periods of time suppresses cancer progression. However, one major challenge in therapeutic applications of H S is its controlled delivery.
View Article and Find Full Text PDFHydrogen sulfide-releasing micelles for promoting angiogenesis.
Polym Chem
July 2020
Kansas State University, Tim Taylor Department of Chemical Engineering, 1005 Durland Hall, 66506, Manhattan Kansas, USA.
Hydrogen sulfide (HS), an important gaseous signalling molecule in the human body, has been shown to be involved in many physiological processes such as angiogenesis. Since the biological activities of HS are known to be significantly affected by the dose and exposure duration, the development of HS delivery systems that enable control of HS release is critical for exploring its therapeutic potential. Here, we prepared polymeric micelles with different HS release profiles, which were prepared from amphiphilic block copolymers consisting of a hydrophilic poly(-acryloyl morpholine) segment and a hydrophobic segment containing HS-releasing anethole dithiolethione (ADT) groups.
View Article and Find Full Text PDFSlow-Release HS Donor Anethole Dithiolethione Protects Liver From Lipotoxicity by Improving Fatty Acid Metabolism.
Front Pharmacol
September 2020
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
"Lipotoxicity" induced by free fatty acids (FAs) plays a central role in the pathogenesis of many metabolic diseases, with few treatment options available today. Hydrogen sulfide (HS), a novel gaseous signaling molecule, has been reported to have a variety of pharmacological properties, but its effect on FAs metabolism remains unclear. The purpose of this study was to investigate the effect and mechanisms of anethole dithiolethione (ADT, a sustained-release HS donor) on hepatic FAs metabolism.
View Article and Find Full Text PDFAnethole Dithiolethione Increases Glutathione in Kidney by Inhibiting -Glutamyltranspeptidase: Biochemical Interpretation and Pharmacological Consequences.
Oxid Med Cell Longev
May 2021
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro 2, I-53100 Siena, Italy.
Aims: Anethole dithiolethione (ADT) is a marketed drug to treat xerostomia. Its mechanism of action is still unknown, but several preclinical studies indicate that it is able to increase intracellular glutathione (GSH) and protect against oxidative stress. Here, we investigated the molecular mechanisms behind these effects.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!