Xenobiotic bioactivation

Ritter JK. Roles of glucuronidation and UDP-glucuronosyltransferases in xenobiotic bioactivation reacts. Chem Biol Interact 2000 129 171-193. 

In the case of reactive intermediate-mediated teratogenesis, the reactive intermediates and ROS are typically too unstable to be formed maternally and cross the placenta. Accordingly, maternal pathways do not contribute directly to this mechanism, whereas the activities of embryonic and fetal enzymes catalyzing xenobiotic bioactivation and the detoxification of xenobiotic reactive intermediates and ROS play a key role in determining the adverse developmental consequences of xenobiotic exposure (see Sect.3 on Reactive intermediate-mediated mechanisms). 

Researchers focused on the metabolically competent human hepatoma cell line HepG2 as a model of human liver. HepG2 cells are a well-known hepatoma cell line that retains many of the morphological characteristics of liver parenchymal cells. This model is often used as a useful tool for HRA/ERA-oriented chemical risk assessment due to the expression of antioxidant and xenobiotic metabolizing enzymes (in particular phase I and phase II enzymes responsible for the bioactivation/detoxification of various xenobiotics) that can be induced or inhibited by dietary and non-dietary agents [28-30]. 

Calu-3 cells have shown the ability to perform fatty acid esterification of budes-onide [132], In pre-clinical studies, this esterification results in a prolonged local tissue binding and efficacy, which is not found when the esterification is inhibited [133]. The precise mechanism remains undefined in that the identity of specific enzyme(s) responsible for this metabolic reaction is unclear [134], Assessment of the potential toxicity and metabolism of pharmaceuticals and other xenobiotics using in vitro respiratory models is still at its infancy. The development of robust in vitro human models (i.e., cell lines from human pulmonary origin) has the potential to contribute significantly to better understanding the role of biotransformation enzymes in the bioactivation/detoxication processes in the lung. 

Ariens EJ, Wuis EW, Veringa EJ. Stereoselectivity of bioactive xenobiotics a pre-Pasteur attitude in medicinal chemistry, pharmacokinetics and clinical pharmacology. Biochem Pharmacol 1988 37 9-18. 

Hepatic necrosis can be classified by the zone of the liver tissue affected. Xenobiotics, such as acetaminophen or chloroform, that undergo bioactivation to toxic intermediates cause necrosis of the cells surrounding the central veins (centrilobular) because the components of the cytochrome P450 system are found in those cells in abundance. At higher doses or in the presence of agents that increase the synthesis of cytochrome P450 (inducers), the area of necrosis may incorporate the... 

Mulder GJ. Drug metabolism inactivation and bioactivation of xenobiotics. In Mulder GJ, Dencker L, eds. Pharmaceutical Toxicology. London, UK Pharmaceutical Press, 2006. 

Glatt H. Sulphotransferases in the bioactivation of xenobiotics. Chem Biol Interact 2000 129 141-170. 

Dekant W, Vamvakas S. Glutathione-dependent bioactivation of xenobiotics. Xenobiotica 1993 23 873-887. 

Although flavonoids can modulate UGT, SULT, and COMT activity toward other xenobiotics, their impact after chronic consumption on their own metabolism has not been examined, even though such activity could substantially alter their bioactivity.105-107 This relationship may become even more complex in older subjects due to the inverse association between age and the adaptability of phase II metabolism.42-108... 

Zhu, B.T., Catechol-O-Methyltransferase (COMT)-mediated methylation metabolism of endogenous bioactive catechols and modulation by endobiotics and xenobiotics Importance in pathophysiology and pathogenesis, Curr Drug Metab., 3, 321, 2002. 

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