Subcellular localization of cytochrome P450, and activities of several enzymes responsible for drug metabolism in the human brain

Aristolochic acid (AA)‐DNA adduct as marker of AA exposure and risk factor for AA nephropathy‐associated cancer

“…This finding is also in line with the demonstration of CYP and NADPH:CYP reductase enzyme activity in the human brain. 15 The absence of AA-DNA adducts in the myocardial tissue of this patient should be added to that previously reported in muscle and skin samples from AAN patients. 4 No AA-DNA adducts were found in the kidney transplant of patient 1, demonstrating that a current exposure to AA can be excluded, at least in patient 1.…”

Contribution of hepatic cytochrome P450 systems to the generation of reactive oxygen species

“…The failure of an iron chelator, deferoxamine, to inhibit NADPHstimulated DCFH oxidation would be in accord with this concept. Since both cytochrome P450 and cytochrome P450 reductase are low in brain [20], the failure of brain ROS production to be enhanced by NADPH does not allow distinction between these two possible sites of response to NADPH. While we found ROS generation to be enhanced markedly by NADPH, another group using liver microsomes found NADPH stimulation of hydroxyl radical generation to occur only in the presence of azide [12].…”

The Blood-Brain Barrier in Epilepsy

“…En passage across the barrier and within the brain, drugs can undergo inactivation and elimination comparable to hepatic drug metabolism. In the brain, the following phase I enzymes have been identified: monoamine oxidases, CYP P450, NADPH-CYP P450 reductase, and epoxide hydrolases (Chat et al, 1998;Dutheil et al, 2010;Ghersi-Egea et al, 1998;Ghersi-Egea et al, 1988;Ghersi-Egea et al, 1993;Minn et al, 1991;Ravindranath et al, 1990). Phase II enzymes identified in the brain include UDP-glucuronosyltransferase (UGT), phenol sulfotransferase (PST), and GST (Dutheil et al, 2010;Ghersi-Egea et al, 1998;Ghersi-Egea et al, 1988;Ghersi-Egea et al, 1993;Minn et al, 1991).…”

“…In the brain, the following phase I enzymes have been identified: monoamine oxidases, CYP P450, NADPH-CYP P450 reductase, and epoxide hydrolases (Chat et al, 1998;Dutheil et al, 2010;Ghersi-Egea et al, 1998;Ghersi-Egea et al, 1988;Ghersi-Egea et al, 1993;Minn et al, 1991;Ravindranath et al, 1990). Phase II enzymes identified in the brain include UDP-glucuronosyltransferase (UGT), phenol sulfotransferase (PST), and GST (Dutheil et al, 2010;Ghersi-Egea et al, 1998;Ghersi-Egea et al, 1988;Ghersi-Egea et al, 1993;Minn et al, 1991). Several phase I and II enzymes have been found in the brain capillary endothelium, where they possibly form a metabolic barrier for drugs en route into the brain (Dutheil et al, 2010;Ghersi-Egea et al, 1998;Ghersi-Egea et al, 1993;Minn et al, 1991;Stamatovic et al, 2008).…”

“…Phase II enzymes identified in the brain include UDP-glucuronosyltransferase (UGT), phenol sulfotransferase (PST), and GST (Dutheil et al, 2010;Ghersi-Egea et al, 1998;Ghersi-Egea et al, 1988;Ghersi-Egea et al, 1993;Minn et al, 1991). Several phase I and II enzymes have been found in the brain capillary endothelium, where they possibly form a metabolic barrier for drugs en route into the brain (Dutheil et al, 2010;Ghersi-Egea et al, 1998;Ghersi-Egea et al, 1993;Minn et al, 1991;Stamatovic et al, 2008). Several reports on metabolism-coupled efflux transport (phase III) suggest that biotransformation of drugs and efflux of the metabolites are part of barrier function.…”