Subanesthetic concentrations of drugs inhibit cytochrome P450-mediated metabolism of aniline

Actions of general anaesthetics and arachidonic acid pathway inhibitors on K+ currents activated by volatile anaesthetics and FMRFamide in molluscan neurones

“…A consistent story emerges if volatile anaesthetics enhance but large alcohols inhibit activities of the relevant cytochrome P450s (in addition to direct effects on the K + channels). Interestingly, it has been found that the cytochrome P450‐mediated aniline hydroxylase activity of rat liver microsomes is stimulated by a number of volatile anaesthetics (Van Dyke & Rikans, 1970; LaBella & Queen, 1995) but inhibited by n ‐alcohols (LaBella & Queen, 1995).…”

Effects of Anesthetics and Terminal Procedures on Biochemical and Hormonal Measurements in Polychlorinated Biphenyl Treated Rats

“…At the time of necropsy, a 2- to 3-g piece of liver was homogenized in 2.5 volumes of ice-cold 0.05 mol/L Tris/1.15% KCI buffer, pH 7.4, and centrifuged at 10 000 g. The supernatant was separated and frozen, and later assayed for EROD, PROD, and BROD activities using the method of Lubet et al 45 Aniline hydroxylase activity was also measured as previously published. 39…”

“…At the time of necropsy, a 2-to 3-g piece of liver was homogenized in 2.5 volumes of ice-cold 0.05 mol/L Tris/1.15% KCI buffer, pH 7.4, and centrifuged at 10 000 g. The supernatant was separated and frozen, and later assayed for EROD, PROD, and BROD activities using the method of Lubet et al 45 Aniline hydroxylase activity was also measured as previously published. 39 a Rats were distributed among 11 treatment groups and were all terminated on experimental day 8, either by decapitation (D) or exsanguination (E) through the abdominal aorta. Group D was decapitated on day 8 and is considered as the control group.…”

“…While PROD and BROD activities have been considered indicators of CYP2B1/2 and 3A activities, respectively, they have been shown to predominantly reflect CYP2B activities. 37 EROD and AH activities were used here as indicator of CYP1A1 and CYP2E activities, 38,39 respectively. Finally, routine clinical biochemistry endpoints were investigated including lactate dehydrogenase (LD), alanine transaminase (ALT), alkaline phosphatise (AP), glucose, total cholesterol, blood urea nitrogen, uric acid, phosphate, and calcium.…”

The site of general anaesthesia and cytochrome P450 oxygenases: similarities defined by straight chain and cyclic alcohols

“…The P450‐mediated oxidation of aniline is executed primarily by isozymes 2E1 and 1A2 and, to a lesser extent, 1A1, 2B1 and 2C11; aniline binds in the P450 heme cavity in another distinctive mode. This catalytic function is much more sensitive than the activities described above to inhibition by the diverse array of anaesthetics (LaBella & Queen, 1995), and its perturbation probably not relevant to the anaesthetic state.…”