Hepatic monooxygenase system

Fent, K., Woodin, B.R., and Stegeman, J.J. (1998). Effects of triphenyl tin and other organotins on hepatic monooxygenase system in fish. In D.R. Livingstone and J.J. Stegeman (Eds.) Forms and Functions of Cytochrome P450, 277-288. 

Gooch, J.W., A.A. Elskus, PJ. Kloepper-Sams, M.E. Hahn, and JJ. Stegman. 1989. Effects of ortho- and non-orf/to-substituted polychlorinated biphenyl congeners on the hepatic monooxygenase system in scup (,Stenotomus chrysops). Toxicol. Appl. Pharmacol. 98 422-433. 

When given orally, 8% of the amaranth is absorbed from the intestinal tract. Intestinal flora have a reducing effect on amaranth, and azo reduction is also mediated by the hepatic monooxygenase system. Aromatic amine metabolites, including 1-amino-4-naphthalene sulfonic acid and l-amino-2-hydro-xy-3,6-naphthalene disulfonic acid, are excreted in the urine and bile. 

The hepatic monooxygenase system is primarily responsible for oxidation of tetrachloroethylene. Thus, compounds that stimulate or induce tetrachloroethylene metabolism could influence the toxicity associated with exposure to this chemical. Results of experiments that have investigated possible enhancement of tetrachloroethylene-induced toxicity by increasing tetrachloroethylene metabolism have been equivocal. Pretreatment of rats with ethanol (Cornish and Adefrrin 1966 Klaassen and Plaa 1966) and phenobarbital (Cornish et al. 1973 Moslen et al. 1977) failed to enhance tetrachloroethylene hepatic toxicity. Pretreatment with polychlorinated biphenyls (PCBs), on the other hand, increased urinary excretion of tetrachloroethylene metabolites in rats and enhanced tetrachloroethylene-induced hepatotoxicity (Moslen etal. 1977). 

Fent, K. and Bucheli, T.D. (1994). Inhibitors of hepatic microsomal monooxygenase system by organotins in vitro in freshwater fish. Aquatic Toxicology 28, 107-126. 

Schwen, R.J. and G.J. Mannering. 1982a. Hepatic cytochrome P-450-dependent monooxygenase systems of the trout, frog and snake. II. Monooxygenase activities. Comp. Biochem. Physiol. 71B 437-443. 

Robacker KM, Kulkarni AP, Hodgson E. 1981. Pesticide induced changes in the mouse hepatic microsomal cytochrome P-450-dependant monooxygenase system and other enzymes. J Environ Sci Health (Part B Pestic Food Contam Agric Wastes) 16(5) 529-546. 

Yarbrough JD, Grimley JM, Alley EG. 1986a. Induction of the hepatic cytochrome P-450 dependent monooxygenase system by cis- and trans-5,10-dihydrogen mirex. Toxicol Lett 32 65-71. 

Mueller and Miller (33) and Brodie et al. (34) were the first to show that enzymes in the microsomal fraction of rat liver could effectively oxidize xenobiotics. Comparable enzymes (aryl hydrocarbon monooxygenases) were later reported in the hepatic tissues of fresh water and marine fish by Creaven et al. (35) and Buhler and Rasmusson (36). Reconstituted hepatic microsomal systems require cytochrome P-450 for monooxygenase activity in both mammals (37) and fish (38,39). Bend et al. 

In an attempt to resolve these questions, we have directed studies toward examining the interaction of chemicals with the hepatic microsomal monooxygenase system of fish and to determine whether multiple forms of hemoprotein(s) P-450 exist, and, if so, how the relative microsomal hemoprotein subpopulations are altered by xen ob i oti cs. 

Other Toxicity Concerns. Additional toxicity concerns include interference with normal metabolism and function of mucosal cells, for example, water absorption by these cells [80]. The unconjugated bile acids are known to block amino acid metabolism [81] and glucose transport [82]. There is a possibility of biotransformation of these enhancers to toxic or carcinogenic substances by hepatic monooxygenases [83]. Absorption of permeation enhancers into the systemic circulation can also cause toxicity, for example, azone [84] and hexamethylene lauramide [85] which are absorbed... 

Imazu, K., Fujishiro, K. Inoue, N. (1992) Effects of dimethylformamide on hepatic microsomal monooxygenase system and glutathione metabolism in rats. Toxicology, ll. 41-50... 

Schenkman, J.B. and Kupfer, D., Eds., Hepatic Cytochrome P-450 Monooxygenase System, Pergamon Press, Oxford, 1982. 

J.B. Schenkman, and D. Kupfer, eds., Hepatic Cytochromr p450 Monooxygenase System, Pergamon Press, Ltd., New York, 1982. 

Microsomes isolated from hepatic tissue appear to retain all of the mixed-function oxidase capabilities of intact hepa-tocytes because of this, microsomal preparations (with the necessary cofactors, e.g.. NADPH. Mg- ) are u.scd frequently for in vitro drug metabolism studies. Because of its membrane-bound nature, the cytochrome P-450 monooxy-gena.se system appears to be housed in a lipoidal environment. This may explain, in part, why lipophilic xenobiotics arc generally good sub.straics for the monooxygenase system. ... 

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