Evidence for the activation of organophosphate pesticides by cytochromes P450 3A4 and 2D6 in human liver microsomes

In Vitro Age-Dependent Enzymatic Metabolism of Chlorpyrifos and Chlorpyrifos-Oxon in Human Hepatic Microsomes and Chlorpyrifos-Oxon in Plasma

“…P450 enzymes implicated in CPF metabolism were consistent with those reported literature (Sams et al, 2000(Sams et al, , 2004Tang et al, 2001;Buratti et al, 2003;Mutch and Williams, 2006;Foxenberg et al, 2007;Croom et al, 2010), and the three primary P450 enzymes responsible for CPF metabolism (CYP2B6, 2C19, and 3A4) follow different age-dependent expression patterns in humans. CYP2B6 was detected in 64% of fetal samples, and levels increased from birth to 1 month old (2-fold), although high variability exists (25-fold) because of both regulatory mechanisms and polymorphisms (Croom et al, 2009).…”

Human Hepatic Cytochrome P450-Specific Metabolism of Parathion and Chlorpyrifos

“…Thus, there remains considerable uncertainty regarding whether variability in metabolism kinetics reflects true age and genetic variability or is an artifact of human liver specimen procurement and storage. The metabolism of selected OPs has also been assessed using specific recombinant human P450s; however, these earlier studies did not report kinetic parameters (K m , V max ) for all reactions (Sams et al, 2000(Sams et al, , 2004Tang et al, 2001;Mutch et al, 2003).…”

“…P450s have also been shown to carry out direct detoxification of the parent compounds through a dearylation reaction (Mutch et al, 2003;Poet et al, 2003). Humans, with their ability to bioactivate OPs, primarily through CYP1A2, 2B6, 2C19, and 3A4, are particularly sensitive to the actions of OPs (Mutch et al, 1999;Sams et al, 2000;Buratti et al, 2003).…”

Do Cytochrome P450 Enzymes Contribute to the Metabolism of Xenobiotics in Human?

“…CYP2B6 plays a major role in pesticides metabolism. CYP2B6 mediates herbicides Ndealkoxylation (Coleman et al, 2000); organophosphate insecticides desulfuration (Foxenberg et al, 2007;Mutch & Williams, 2006;Buratti et al, 2005;Leoni et al, 2008;Sams et al, 2000;); orghanochlorine and carbamate insecticides sulfoxidation (Abass et al, 2010;Casabar et al, 2006;; fungicide metalaxyl Odemethylation and lactone formation (Abass et al, 2007b).…”

“…Dextromethrophan O-demethylation is the most used in vitro model reaction for CYP2D6 activity (Kronbach et al 1987, Park et al 1984. Known pesticide substrates for CYP2D6 include phosphorothioate insecticides (Mutch et al 2003, Mutch & Williams 2006, Sams et al 2000, Usmani et al 2004b as well as (Johnson and Burlew, 1996;Volotinen et al, 2007) carbamate insecticide (Tang et al, 2002). CYP2D6 is also involved in the N-dealkylation of the atrazine and diuron herbicides (Lang et al, 1997;Abass et al, 2007c).…”