Cytochrome P-450 Enzyme System

Publication Title: 
American Journal of Physiology. Endocrinology and Metabolism

Xenobiotic metabolism has been proposed to play a role in modulating the rate of aging. Xenobiotic metabolizing enzymes (XME) are expressed at higher levels in calorically restricted mice (CR) and in GH/IGF-I-deficient, long-lived mutant mice. In this study, we show that many phase I XME genes are similarly upregulated in additional long-lived mouse models, including "crowded litter" (CL) mice, whose lifespan has been increased by food restriction limited to the first 3 wk of life, and in mice treated with rapamycin.

Author(s): 
Steinbaugh, Michael J.
Sun, Liou Y.
Bartke, Andrzej
Miller, Richard A.
Publication Title: 
Molecular Psychiatry

The last decade of research into the pharmacogenetics of antipsychotics has seen the development of genetic tests to determine the patients' metabolic status and the first attempts at personalization of antipsychotic treatment. The most significant results are the association between drug metabolic polymorphisms, mainly in cytochrome P450 genes, with variations in drug metabolic rates and side effects. Patients with genetically determined CYP2D6 poor metabolizer (PMs) status may require lower doses of antipsychotic.

Author(s): 
Arranz, M. J.
de Leon, J.
Publication Title: 
Psychiatry and Clinical Neurosciences

Central nervous system disorders are the third greatest health problem in developed countries, and schizophrenia represents some of the most disabling ailments in young individuals. There is an abuse and/or misuse of antipsychotics, and recent advances in pharmacogenomics pose new challenges for the clinical management of this complex disorder. Schizophrenia is a multi-factorial/polygenic complex disorder in which hundreds of different genes are potentially involved, leading to the phenotypic expression of the disease in conjunction with epigenetic and environmental phenomena.

Author(s): 
Cacabelos, RamÛn
Hashimoto, Ryota
Takeda, Masatoshi
Publication Title: 
Phytotherapy research: PTR

The field of genetics, which includes the use of 'omic' technologies, is an evolving area of science that has emerging application in phytotherapy. Omic studies include pharmacogenomics, proteomics and metabolomics. Herbal medicines, as monotherapies, or complex formulations such as traditional Chinese herbal prescriptions, may benefit from omic studies, and this new field may be termed 'herbomics'.

Author(s): 
Sarris, Jerome
Ng, Chee Hong
Schweitzer, Isaac
Publication Title: 
Research Communications in Chemical Pathology and Pharmacology

Experiments were conducted to examine the effect of manganese on drug response and metabolism in male and female rats. Three days after administration of manganese chloride (5 mg Mn/kg, ip), the duration of hexobarbital hypnosis was prolonged in male but not in female rats. Hepatic microsomal metabolism of aniline, ethylmorphine, and hexobarbital was significantly inhibited in male rats. Metabolism of aniline and ethylmorphine was also inhibited in female rats but to a lesser extent than in males. Hexobarbital metabolism was not inhibited in female rats.

Author(s): 
Schnell, R. C.
Deimling, M. J.
Publication Title: 
Journal of Environmental Pathology, Toxicology and Oncology: Official Organ of the International Society for Environmental Toxicology and Cancer

The effect of chlordimeform treatment on the hepatic microsomal drug metabolizing enzymes was examined in male and female rats following either acute or repeated treatment.

Author(s): 
Budris, D. M.
Yim, G. K.
Schnell, R. C.
Publication Title: 
Fundamental and Applied Toxicology: Official Journal of the Society of Toxicology

Experiments were conducted to examine the effect of manganese on the hepatic mixed function oxidase system in the rat. Acute treatment with manganese chloride (1-10 mg Mn/kg, ip) produced a significant prolongation of hexobarbital hypnosis in male rats on Days 2 and 3 following metal administration. The threshold dose of manganese to produce this alteration in response was 5 mg Mn/kg and the altered response returned to control values by Day 5.

Author(s): 
Deimling, M. J.
Schnell, R. C.
Publication Title: 
Journal of Pharmacobio-Dynamics

Following in vivo treatment with carrageenan, sex-related differences in alteration of hepatic drug metabolism were found in the rat. In adult male rats, marked decreases were observed in hepatic 9000 x g supernatant cytochrome P-450 content and in the biotransformation of hexobarbital, aminopyrine, ethylmorphine, and meperidine. Hexobarbital hypnosis was significantly prolonged by carrageenan treatment in intact and testectomized animals as compared to their respective controls.

Author(s): 
Ishikawa, M.
Sasaki, K.
Ozaki, M.
Takayanagi, Y.
Sasaki, K.
Publication Title: 
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi = Chinese Journal of Parasitology & Parasitic Diseases

In this paper, the effect of Schistosoma japonicum infection on liver drug-metabolizing enzymes of mice was studied. The prolongation of hypnosis duration of sodium pentobarbital in vivo and the inhibition of liver aniline hydroxylase (AH), aminopyrine N-demethylase (APD) as well as cytochrome P-450 (Cyt P-450) in vitro were observed in mice infected with 20, 40 and 60 cercariae of S. japonicum after 6 weeks.

Author(s): 
Wang, J.
Qiu, Z. Y.
Xie, W.
Wu, Y. Y.
Publication Title: 
The Journal of Nutritional Biochemistry

The present studies characterized the influence of dietary selenium (Na2SeO3) on the duration of pentobarbital (PB) induced hypnosis (sleep) in the rat. Rats were fed semipurified diets varying from 0.01 to 2.0 mg Se/kg for up to 4 weeks. Consumption of diets containing 1.0 and 2.0 mg Se/kg significantly prolonged PB induced hypnosis. Hepatic selenium, but not hepatic glutathione peroxidase activity, correlated with the length of PB induced hypnosis. The prolongation of hypnosis caused by diets containing 1.0 mg Se/kg was substantially reduced or eliminated by repeated exposure to PB.

Author(s): 
Debski, Bogdan
Milner, John A.

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