“Commandeuring” Xenobiotic Metabolism: Advances in Understanding Xenobiotic Metabolism

Abstract

The understanding of how exogenous chemicals (xenobiotics) are metabolized, distributed, and eliminated is critical to determine the impact of the chemical and its metabolites to the (human) organism. This is part of the research and educational discipline ADMET (absorption, distribution, metabolism, elimination, and toxicity). Here, we review the work of Jan Commandeur and colleagues who have not only made a significant impact in understanding of phase I and phase II metabolism of several important compounds but also contributed greatly to the development of experimental techniques for the study of xenobiotic metabolism. Jan Commandeur’s work has covered a broad area of research, such as the development of online screening methodologies, the use of a combination of enzyme mutagenesis and molecular modeling for structure–activity relationship (SAR) studies, and the development of novel probe substrates. This work is the bedrock of current activities and brings the field closer to personalized (cohort-based) pharmacology, toxicology, and hazard/risk assessment.

A method to determine reactive oxygen species production in intestinal and liver cell cultures using the 2′,7′-dichlorodihydrofluorescein diacetate assay

“…In those tissues parent compounds and their metabolites are absorbed in the gastrointestinal tract (GIT), which represents the most common exposure route for xenobiotics [4] . After absorption in the GIT, the liver is the main organ responsible for the metabolism of xenobiotics including phase I and II biotransformation reactions which increase the production of ROS [5] . Therefore, intestinal and liver cells are especially susceptible to chemical injury when exposed to pollutants.…”

In silico Evaluation of the Inhibitory Potential of Cymbopogonol from Cymbopogon citratus Towards Falcipain-2 (FP2) Cysteine Protease of Plasmodium falciparum

“…Phase I drug metabolism is facilitated by the isoenzyme superfamily cytochrome P450 (CYP), which catalyzes a number of metabolic reactions. 43 One of the main causes of pharmacokinetics-related drugdrug interactions is the suppression of the five major isoforms CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4, which eventually become the substrates of pharmaceuticals. 37,44 .…”

Real-time fluorescent monitoring of phase I xenobiotic-metabolizing enzymes

“…3,4 Within the human body, various enzymes are intricately involved in the metabolism and excretion of xenobiotics, encompassing drugs, pollutants, cosmetics, and diverse nutrients. 5 Exogenous xenobiotics present a substantial risk to both human health and the environment due to their carcinogenicity, propensity for accumulation, and inherent toxicity. 6 Prolonged exposure to these substances at elevated concentrations may result in chronic abnormalities, including but not limited to growth retardation, immunological and neurological impairments, learning difficulties, reproductive problems, and the manifestation of various human diseases such as Parkinson's and Alzheimer's.…”