Metabolizing enzymes, xenobiotic

Microbial Transformations and Interactions with the Xenobiotic Metabolizing Enzyme (XME) System... 

Figure 3 Some interactions between gastrointestinal bacteria and the xenobiotic metabolizing enzyme system of the host. Solid lines, host XME system reactions dotted lines, classes of reactions mediated by gastrointestinal bacteria. Specific examples of reaction classes 1-5 are cited in the text. (Modified from Rowland and Tanaka " )...

Intake of various xenobiotics such as phenobarbital, PCBs, or certain hydrocarbons can cause enzyme induction. It is thus important to know whether or not an individual has been exposed to these inducing agents in evaluating biochemical responses to xenobiotics. Metabolites of certain xenobiotics can inhibit or stimulate the activities of xenobiotic-metabolizing enzymes. 

To date, there is very little known about if and how phytochemicals modulate the metabolism of GIT tissues other than the liver. Of particular interest are the xenobiotic metabolizing enzymes of the GIT, which are involved with transformation of drugs and toxins. Whereas the metabolic activities of the resident microflora dominate in the large intestine, mucosal enzyme activities are more important in the small intestine where bacterial densities are lower and the villi and microvilli increase the area of exposure. 

Studies on rats had shown no toxicity of astaxanthin preparations. Dietary administration of astaxanthin has proved to significantly inhibit carcinogenesis in the mouse urinary bladder, rat oral cavity, and rat colon. In addition, it is reported to induce xenobiotic-metabolizing enzymes in rat liver. 

Gradelet, S. et al., Effects of canthaxanthin, astaxanthin, lycopene and lutein on Ever xenobiotic-metabolizing enzymes in the rat, Xenobiotica, 26, 49, 1996. 

Donnarumma L, G de Angelis, F Gramenzi, L Vittozzi (1988) Xenobiotic metabolizing enzyme systems in test fish. III. Comparative studies of liver cytosolic glutathione S-transferases. Ecotoxicol Environ Saf 16 180-186. 

Researchers focused on the metabolically competent human hepatoma cell line HepG2 as a model of human liver. HepG2 cells are a well-known hepatoma cell line that retains many of the morphological characteristics of liver parenchymal cells. This model is often used as a useful tool for HRA/ERA-oriented chemical risk assessment due to the expression of antioxidant and xenobiotic metabolizing enzymes (in particular phase I and phase II enzymes responsible for the bioactivation/detoxification of various xenobiotics) that can be induced or inhibited by dietary and non-dietary agents [28-30]. 

Iscan, M., T. Coban, and B.C. Eke. 1992. Responses of hepatic xenobiotic metabolizing enzymes of mouse, rat and guinea-pig to nickel. Pharmacol. Toxicol. 71 434-442. 

Egaas, E., J.U. Skaare, N.O. Svendsen, M. Sandvik, J.G. Falls, W.C. Dautennan, T.K. Collier, and J. Netland. 1993. A comparative study of effects of atrazine on xenobiotic metabolizing enzymes in fish and insect, and of the in vitro phase II atrazine metabolism in some fish, insects, mammals and one plant species. Comp. Biochem. Physiol. 106C 141-149. 

Hektoen, H., A. Bernhoft, K. Ingebrigtsen, J.U. Skaare, and A. Goksoyr. 1994. Response of hepatic xenobiotic metabolizing enzymes in rainbow trout (Oncorhynchus mykiss) and cod (Gadus morhua) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). Aquat. Toxicol. 28 97-106. 

Bemhoft, A., I. Nafstad, P. Engen, and J.U. Skaare. 1994. Effects of pre- and postnatal exposure to 3,3, 4,4, 5-pentachlorobiphenyl on physical development, neurobehavior and xenobiotic metabolizing enzymes in rats. Environ. Toxicol. Chem. 13 1589-1597. 

Skaare, J.U., E.G. Jensen, A. Goksoyr, and E. Egaas. 1991. Response of xenobiotic metabolizing enzymes of rainbow trout (Oncorhynchus mykiss) to the mono -ortho substituted polychlorinated PCB congener 2,3,4,4,5-pentachlorobiphenyl, PCB-118, detected by enzyme activities and immunochemical methods. Arch. Environ. Contam. Toxicol. 20 349-352. 

Collier, T.K. and U. Varanasi. 1991. Hepatic activities of xenobiotic metabolizing enzymes and biliary levels of xenobiotics in English sole (Parophrys vetulus) exposed to environmental contaminants. Arch. Environ. Contam. Toxicol. 20 462-473. 

Lamartiniere CA, Nicholas JM. 1984. Neonatal chlordecone alteration of the ontogeny of sex-differentiated hepatic drug and xenobiotic metabolizing enzymes. Biochem Pharmacol 33(24) 4092-4095. 

Willey JC, Coy E, Brolly C, Utell MJ, Frampton MW, Hammersley J, Thilly WG, Olson D, Cairns K (1996) Xenobiotic metabolism enzyme gene expression in human bronchial epithelial and alveolar macrophage cells. Am J Respir Cell Mol Biol 14(3) 262-271. 

Hukkanen J, Pelkonen O, Raunio H (2001) Expression of xenobiotic-metabolizing enzymes in human pulmonary tissue possible role in susceptibility for ILD. Eur Respir J Suppl 32 122s-l26s... 

Because of its preference for monoamine-like molecules and its role in the metabolism of many psychoactive compounds, CYP2D6 is perhaps the most interesting of the xenobiotic metabolizing enzymes to be implicated in the human brain. As such, a great deal of information is now available regarding its presence there (O Table 3-3). 

Chaturvedi (1993) also examined the effect of mixtures of 10 pesticides (alachlor, aldrin, atrazine, 2,4-D, DDT, dieldrin, endosulfan, lindane, parathion, and toxaphene) administered by oral intubations or by drinking water on the xenobiotic-metabolizing enzymes in male mice. He concluded, The pesticide mixtures have the capability to induce the xenobiotic-metabolizing enzymes, which possibly would not have been observed with individual pesticides at the doses and experimental conditions used in the study. ... 

Lloyd SA, Franklin MR. 1991. Modulation of carbon tetrachloride hepatoxicity and xenobiotic-metabolizing enzymes by corticosterone pretreatment, adrenalectomy and sham surgery. Toxicol Lett 55 65- 75. 

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