Phenobarbital Induction of

Waxman DJ, Azarnoff L. Phenobarbital induction of cytochrome P450 gene expression. Biochem J 1992 281 577. 

Kakizaki, S., Y. Yamamoto, A. Ueda, R. Moore, T. Sueyoshi, and M. Negishi. Phenobarbital induction of drug/steroid-metabolizing enzymes and nuclear receptor CAR. Biochim. Biophys. Acta 1619 239-242, 2003. 

Waxman DJ, Morrissey JJ, Naik S, et al. Phenobarbital induction of cytochrome P450 high-level long-term responsiveness of primary rat hepatocyte cultures to drug induction, and glucocorticoid dependence of the phenobarbital response. Biochem J 1990 271 113-119. 

In experimental animals, other factors that can cause an increase in selenium levels in expired air are higher dietary levels of selenium, protein, or methionine (Ganther et al. 1966). Phenobarbital induction of microsomal enzymes has also led to increased exhalation of selenium following intravenous administration of sodium selenite (Sternberg et al. 1968). 

Waxman, D.J. and AzarofF, L. (1992) Phenobarbital induction of cytochrome P-450 gene expression. The Biochemical Journal, 281, 577-592. 

Rencurel, F., Stenhouse, A., Hawley, S. A., Friedberg, T., Hardie, D. G., Sutherland, C., and Wolf, C. R. (2005) AMP-activated protein kinase mediates phenobarbital induction of CYP2B gene expression in hepatocytes and a newly derived human hepatoma cell line. /. Biol. Chem. 280, 4367-4373. 

GH pattern. GH suppression is also a key determinant of the lower responsiveness of female rats to phenobarbital induction of CYP2B1 (refs... 

Narhi, L.O. and A.J. Fulco (1982). Phenobarbital induction of a soluble cytochrome P450 dependent fatty acid monooxygenase from Bacillus megaterium. J. Biol. Chem. 257, 2147-2150. 

Ourlin JC, Handschin C, Kaufmann M, Meyer UA. A Link between cholesterol levels and phenobarbital induction of cytochromes P450. Biochem Biophys Res Commun 2002 291 378-384. 

Narhi LO, Fulco AJ (1982) Phenobarbital induction of a soluble cytochrome P-450-dependent fatty acid monooxygenase in Bacillus megaterium. J Biol Chem 257 2147-2150... 

DJ Waxman, L Azaroff. Phenobarbital induction of cytochrome P-450 gene expression. 

The induction of P450s belonging to family CYP2 by phenobarbital and other inducing agents is accompanied by proliferation of the endoplasmic reticulum and... 

Apart from monooxygenases, other enzymes concerned wih xenobiotic metabolism may also be induced. Some examples are given in Table 2.5. Induction of glucuronyl transferases is a common response and is associated with phenobarbital-type induction of CYP family 2. Glutathione transferase induction is also associated with this. A variety of compounds, including epoxides such as stilbene oxide and... 

Schoor, W.P. and M. Srivastava, 1984. Position-specific induction of benzo[a]pyrene metabolism by 3-meth-ylcholanthrene and phenobarbital in mullet (Mugil cephalus), a marine fish. Comp. Biochem. Physiol. 73C 391-396. 

The levels of exposure to phenobarbital in humans from therapeutic uses are comparable to serum levels that produce tumorigenic effects achieved in animals. Based on these analyses, the first key event, induction of CYP isoforms (CYP3A as well as CYP2B), occurs in humans at the levels of exposure that humans attain... 

Based on the in vitro results and the rat in vivo studies at different exposure levels, induction of CYP isoforms in human hepatocytes is considerably lower for metofluthrin than phenobarbital at identical concentrations [115, 116]. 

In this study, P-450-related enzyme activities (benzphetamine N-demethylase, 7-ethoxycoumarin O-deethylase) were also measured in liver homogenates (prepared 24 hours after the last treatment) from rats treated orally with MEK for 1-7 days and compared to the activity obtained with phenobarbital treatment (80 mg/kg intraperitoneally for 3 days) (Robertson et al. 1989). Total cytochrome P-450 was also measured. No consistent change was noted in benzphetamine N-demethylase activity as the result of MEK treatment, while 7-ethoxycoumarin O-deethylase was over 3 times higher than controls and comparable to phenobarbital induction. Total P-450 levels were increased to approximately 150-200% of controls with MEK and to 570% of control by phenobarbital. The authors concluded that the potentiating effects of MEK on the neurotoxicity of -hexane appear to arise, at least in part, from the activating effects of MEK on selected microsomal enzymes responsible for -hexane activation. 

Rats pretreated with xylene or phenobarbital and then exposed to -hexane by inhalation exhibited a markedly increased peak serum concentration of 2,5-hexanedione (Toftgard et al. 1983). Peak serum concentrations were approximately 4 g/mL in control rats, 11 g/mL in xylene-induced rats, and 13 g/mL in phenobarbital-induced rats. Peaks were reached in 1-2 hours. The half-life for elimination from serum was approximately one hour for both pretreated and untreated rats. The high serum 2,5-hexanedione concentrations were correlated with an induction of liver microsomal P-450 content (0.56 nmol/mg protein in control rats, 1.03 nmol/mg in xylene-induced rats, and 1.7 nmol/mg protein in phenobarbital-induced rats, respectively). 

Sladek, N.E. and Mannering, G.J. (1969) Induction of drug metabolism. I. Differences in the mechanisms by which polycyclic hydrocarbons and phenobarbital produce their inductive effects on microsomal N-demethylating systems. Molecular Pharmacology, 5 (2), 174-185. 

DuBois KP, Kinoshita FK. 1968. Influence of induction of hepatic microsomal enzymes by phenobarbital on toxicity of organic phosphate insecticides. Proc Soc Exp Biol Med 129 699-702. 

Alvares, A.P., Schilling, G., Levin, W. and Kuntzman, R. Studies on the induction of CO-binding pigments in liver microsomes by phenobarbital and 3-methylcholanthrene. 

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