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Keywords = MDMH

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18 pages, 2423 KB  
Article
Toxicokinetic Characterization of MDM Hydantoin via Stable Metabolite DMH: Population Modeling for Predicting Dermal Formaldehyde Formation
by Woohyung Jung, Jaewoong Lee, Woojin Kim, Seongwon Kim, Woojin Nam, In-Soo Myeong, Kwang Ho Kim, Soyoung Shin and Tae Hwan Kim
Toxics 2025, 13(11), 917; https://doi.org/10.3390/toxics13110917 - 25 Oct 2025
Viewed by 251
Abstract
MDM hydantoin (MDMH), a formaldehyde-releasing preservative widely used in cosmetics, poses potential health risks due to its conversion to formaldehyde and systemically absorbed metabolites. Current safety assessments lack quantitative exposure data due to rapid degradation of MDMH in biological matrices. In the present [...] Read more.
MDM hydantoin (MDMH), a formaldehyde-releasing preservative widely used in cosmetics, poses potential health risks due to its conversion to formaldehyde and systemically absorbed metabolites. Current safety assessments lack quantitative exposure data due to rapid degradation of MDMH in biological matrices. In the present study, we developed a validated LC-MS/MS assay for simultaneous determination of MDMH and its stable metabolite DMH in rat plasma, and characterized their toxicokinetics using population modeling following intravenous and transdermal administration. MDMH exhibited extremely rapid elimination (t1/2 = 0.4 ± 0.1 min) with near-complete conversion to DMH (97.6 ± 9.6%), while DMH demonstrated prolonged retention (t1/2 = 174.2 ± 12.2 min) and complete bioavailability (100.9 ± 18.0%) after transdermal application. Population modeling estimated that 84% (relative standard error: 42.8%) of applied MDMH undergoes cutaneous absorption and metabolism to DMH and formaldehyde within skin tissues. This study demonstrates that stable metabolite monitoring combined with population modeling enables toxicokinetic characterization of rapidly degrading compounds following dermal exposure. Full article
(This article belongs to the Special Issue Advances in Computational Methods of Studying Exposure to Chemicals)
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13 pages, 2720 KB  
Article
The Repurposing of FDA-Approved Drugs as FtsZ Inhibitors against Mycobacterium tuberculosis: An In Silico and In Vitro Study
by Andrea Michel Tovar-Nieto, Luis Enrique Flores-Padilla, Bruno Rivas-Santiago, Juan Valentin Trujillo-Paez, Edgar Eduardo Lara-Ramirez, Yolanda M. Jacobo-Delgado, Juan Ernesto López-Ramos and Adrián Rodríguez-Carlos
Microorganisms 2024, 12(8), 1505; https://doi.org/10.3390/microorganisms12081505 - 23 Jul 2024
Cited by 3 | Viewed by 2489
Abstract
Mycobacterium tuberculosis (Mtb), the causative pathogen of tuberculosis, remains one of the leading causes of death from a single infectious agent. Furthermore, the growing evolution to multi-drug-resistant (MDR) strains requires de novo identification of drug targets for evaluating candidates or repurposing drugs. Hence, [...] Read more.
Mycobacterium tuberculosis (Mtb), the causative pathogen of tuberculosis, remains one of the leading causes of death from a single infectious agent. Furthermore, the growing evolution to multi-drug-resistant (MDR) strains requires de novo identification of drug targets for evaluating candidates or repurposing drugs. Hence, targeting FtsZ, an essential cell division protein, is a promising target. Methods: Using an in silico pharmacological repositioning strategy, four FDA-based drugs that bind to the catalytic site FtsZ were selected. The Alamar Blue colorimetric assay was used to assess antimicrobial activity and the effect of drugs on Mtb growth through growth curves. Bacterial load was determined with an in vitro infection model using colony-forming units (CFU)/mL, and cytotoxicity on human monocyte-derived macrophages (MDMhs) was assessed by flow cytometry. Results: Paroxetine and nebivolol exhibited antimycobacterial activity against both reference TB and MDR strains at a concentration of 25 µg/mL. Furthermore, both paroxetine and nebivolol demonstrated a significant reduction (p < 0.05) in viable bacteria compared to the untreated group in the in vitro infection model. Conclusions: Collectively, our findings demonstrate that the use of paroxetine and nebivolol is a promising strategy to help in the control of tuberculosis infection. Full article
(This article belongs to the Special Issue Prevention, Treatment and Diagnosis of Tuberculosis, 2nd Edition)
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