Liver xenobiotic metabolism

Gradelet, S., P. Astorg, J. Leclerc et al. 1996. Effects of canthaxanthin, astaxanthin, lycopene and lutein on liver xenobiotic-metabolizing enzymes in the rat. Xenobiotica 26(1)49-63. 

O. mykiss 10 After 14 days, no adverse effects on survival, growth, or liver xenobiotic metabolizing activities 16... 

Single ip injection of 5 mg/kg BW Rapid increase in certain liver xenobiotic metabolizing 29 enzymes (AHH), but no increase in GSH and epoxide hydrolase — even up to 42 days after exposure... 

Astorg P, Gradelet S, Leclerc J, Canivenc MC, Siess MH. 1994. Effects of beta-carotene and canthaxanthin on liver xenobiotic-metabolizing enzymes in the rat. Food Chem. Toxicol. 32 735 12... 

Lodovici M, Aiolli S, Monserrat C, et al. 1994. Effect of mixture of 15 commonly used pesticides on DNA levels of 8-hydroxy-2-deoxyguanosine and xenobiotic metabolizing enz5mies in rat liver. J Environ Pathol Toxicol and Oncol 13 163-168. 

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. 

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]. 

Hakkola, J., Pasanen, M., Purkunen, R., Saarikoski, S., Pelkonen, O., Maenpaa, J., Rane, A. and Raunio, H. (1994) Expression of xenobiotic-metabolizing cytochrome P450 forms in human adult and fetal liver. Biochemical Pharmacology, 48 (1), 59-64. 

Hepatic mixed-function oxidase activities demonstrated seasonal trends, with higher specific activities in the cold weather months in both populations with few differences in enzyme activities or cytochrome levels between the two populations. Metabolism of aldrin, dieldrin and DDT was similar between the two populations. R fish have larger relative liver size and, therefore, a greater potential for xenobiotic metabolism. However, biotransformation appears to be of minor importance in chlorinated alicyclic insecticide resistance in mosquitofish barriers to penetration appear to be of greater importance and an implied target site insensitivity appears to be the most important factor in resistance. 

N. W. McCracken, P. G. Blain, F. M. Williams, Human Xenobiotic Metabolizing Esterases in Liver and Blood , Biochem. Pharmacol. 1993, 46, 1125-1129. 

Johri A, Dhawan A, Lakhan Singh R, Parmar D. 2006. Effect of prenatal exposure of deltamethrin on the ontogeny of xenobiotic metabolizing cytochrome P450s in the brain and liver of offsprings. Toxicol Appl Pharmacol 214 ... 

Carlson, G.P. Day, B.J. (1992) Induction by pyridine of cytochrome P450IIE1 and xenobiotic metabolism in rat lung and liver. Pharmacology, 44, 117-123... 

A recent paper clearly highlighted the limitations of in vitro systems in modeling whole-organism responses, which should be considered when developing biomarkers of in vivo toxicity. Dere and colleagues (58) compared the temporal gene expression profiles of Hepalclc mouse hepatoma cells and of the mice liver after treatment with a dioxin. The analysis revealed that Hepalclc cells were able to model the induction of xenobiotic metabolism in vivo. On the other hand, responses associated with cell cycle progression and proliferation were unique to the in vitro system, while lipid metabolism and immune responses were not replicated effectively in the Hepalclc cells. 

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