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Use of physiologically based kinetic modeling to predict neurotoxicity and genotoxicity of methylglyoxal in humans

Medicine and Health

Use of physiologically based kinetic modeling to predict neurotoxicity and genotoxicity of methylglyoxal in humans

L. Zheng, X. Li, et al.

This study by Liang Zheng, Xiyu Li, Frances Widjaja, Chen Liu, and Ivonne M. C. M. Rietjens explores the neurotoxicity and genotoxicity risks associated with methylglyoxal (MGO). Using advanced PBK modeling and reverse dosimetry, the research reveals intriguing insights about dietary and endogenous MGO intake, emphasizing the importance of risk assessment in different populations.

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Playback language: English
Abstract
This study used physiologically based kinetic (PBK) modeling and reverse dosimetry to assess human neurotoxicity and genotoxicity risks from methylglyoxal (MGO). A human PBK model, developed based on a mouse model, translated in vitro toxicity data from human stem cell-derived neurons and melanoma cells into in vivo dose-response predictions. Results showed that dietary MGO intake did not pose a neurotoxicity concern, but genotoxicity concerns could not be excluded. Endogenous MGO formation, especially in diabetics, raised concerns for both genotoxicity and some neurotoxicity endpoints, highlighting the importance of considering endogenous levels in MGO risk assessment.
Publisher
npj Science of Food
Published On
Oct 06, 2024
Authors
Liang Zheng, Xiyu Li, Frances Widjaja, Chen Liu, Ivonne M. C. M. Rietjens
Tags
methylglyoxal
neurotoxicity
genotoxicity
PBK modeling
risk assessment
endogenous formation

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