Hepatic mixed-function oxidase

Acetaminophen, which depletes hepatic glutathione, does not potentiate the toxicity of methyl parathion in mice. A possible mechanism of action may be competition between acetaminophen and methyl parathion for mixed function oxidases and subsequent prevention of activation of methyl parathion to methyl paraoxon (Costa and Murphy 1984). Diethyl maleate, an agent that depletes cytosolic glutathione and is not an enzyme inducer, potentiates toxicity of methyl parathion in mice (Mirer et al. 1977). 

Tyagi SR, Sing Y, Srivastava PK, et al. 1984. Induction of hepatic mixed function oxidase system by endosulfan in rats. Bull Environ Contam Toxicol 32 550-556. 

By enhancing the metabolism of trichloroethylene to its cytotoxic metabolites, compounds that induce the hepatic mixed-function oxidase system can potentiate the hepatotoxicity of trichloroethylene. 

NS (acute) (general population) Hepatic Decreased mixed function oxidase activity NS (children) Alvares et al. 1975 Saenger et al. 1984... 

L The answer is d. (Hardman, p 906.) Cimetidine slows the metabolism of Ca channel blockers, which are substrates for hepatic mixed-function oxidases. Inhibition of cytochrome P450 activity is peculiar to cimetidine and is not a mechanism of action of other histamine 2 (Hz) blockers. 

Diarrhea, reduced food and water consumption, body weight loss, decreased blood glucose levels, and disrupted hepatic microsomal mixed function oxidases in mice receiving 10 mg/kg body weight daily (Fujimori et al. 1983). 

Many commercial lots of technical PCP are known to contain small — but possibly biologically significant — amounts of highly toxic dioxins, dibenzofurans, and hexachlorobenzene. These contaminants may be responsible for most of the toxicity of technical PCP preparations (McConnell et al. 1980 Parker et al. 1980 Wollesen et al. 1986 Holsapple et al. 1987). However, both technical-and analytical-grade PCP can induce hepatic mixed-function oxidases in intoxicated rats and cattle. In cattle, this effect was observed in both calves and adults, and in hepatic as well as pulmonary microsomes, and seemed to be dose related (Shull et al. 1986). 

Elliott, J.E., S.W. Kennedy, D. Jeffrey, and L. Shutt. 1991. Polychlorinated biphenyl (PCB) effects on hepatic mixed function oxidases and porphyria in birds. II. American kestrel. Comp. Biochem. Physiol. 99C 141-145. 

Fabacher, D.L. and P.C. Baumann. 1985. Enlarged livers and hepatic microsomal mixed-function oxidase components in tumor-bearing brown bullheads from a chemically contaminated river. Environ. Toxicol. Chem. 4 703-710. 

Gerhart, E.H. and R.M. Carlson. 1978. Hepatic mixed-function oxidase activity in rainbow trout exposed to several polycyclic aromatic compounds. Environ. Res. 17 284-295. 

Robertson P, White EL, Bus JS. 1989. Effects of methyl ethyl ketone pretreatment on hepatic mixed-function oxidase activity and on in vivo metabolism of -hexane. Xenobiotica 19(7) 721-729. 

Knights KM, Gourlay GK, Cousins MJ. Changes in rat hepatic microsomal mixed function oxidase activity following exposure to halothane under various oxygen concentrations. Biochem Pharmacol 1987 36(6) 897-906. 

Freudenthal, R., Leber, P., Emmerling, D., Kerchner, G. and Campbell, D. (1976). Characterization of the hepatic microsomal mixed-function oxidase system in miniature pigs. Drug Metab. Dispos. 4 25-27. 

Hartgrove RW Jr., Hundley SG, Webb RE. 1977. Characterization of the hepatic mixed function oxidase system in endrin-resistant and -susceptible pine voles. Pesticide Biochemistry and Physiology 7 146-153. 

Baker RC, Coons LB, Mailman RB, et al. 1972. Induction of hepatic mixed function oxidases by the insecticide mirex. Environ Res 5 418-424. 

Fabacher DL, Hodgson E. 1976. Induction of hepatic mixed-function oxidase enzymes in adult and neonatal mice by Kepone and mirex. Toxicol Appl Pharmacol 38 71-77. 

Madhukar BV, Matsumura F. 1979. Comparison of induction patterns of rat hepatic microsomal mixed-function oxidases by pesticides and related chemicals. Pestic Biochem Physiol 11(1-3)301-308. 

Mehendale HM, Chen PF, Fishbein L, et al. 1973. Effect of mirex on the activities of various rat hepatic mixed-function oxidases. Arch Environ Contam Toxicol 1(3) 245-254. 

Mehendale HM, Takanaka A, Desaiah D, et al. 1977a. Kepone induction of hepatic mixed function oxidases. Life Sci 20(6) 991-997. 

Peppriell J. 1981. The induction of hepatic microsomal mixed-function oxidase activities in the mouse by mirex, 3,4,5,3 ,4 ,5 -hexachlorobiphenyl, and equimolar dosages of both. Environ Res 26 402-408. 

Hildebrandt A., Estabrook RW. 1971. Evidence for the participation of cytochrome b5 in hepatic microsomal mixed-function oxidase reactions. Arch Biochem Biophys 143 66-79. 

Table II summarizes the results together with the detailed experimental conditions. As is evident, metabolic activities were detectable in these 3 aquatic species, but the rate was far lower as compared with mammalian hepatic enzume preparations, and the oxidative activities in snail were particularly low although the possibility was not ruled out of the presence of inhibitors of mixed-function oxidases in the fractions. The O-demethylation reaction proceeds extremely slowly in the enzyme preparation of aquatic animals, at less than one hundredth that of mammals.

Enzymes of the hepatic microsomes of most marine organisms, with the notable exception of certain molluscs, metabolize xeno-biotic substrates however, as much as 600-fold variations in enzyme activities have been noted between different species of marine teleosts (40). The hepatic enzyme activities of aquatic species are generally lower, with most substrates tested, than the hepatic enzymes of mammals (40). The mixed function oxidase enzymes in marine organisms are inducible by hydrocarbons, such as 3-methylcholanthrene or benzo[a]pyrene. Moreover, it is known... 

Molinate Metabolism in Carp Hepatic Mixed-function Oxidase System. Incubation of molinate with carp liver microsomes produced four major organosoluble metabolites (molinate sulfoxide, 3- and 4-hydroxy molinate, and keto HMI). Parameters affecting... 

Seasonal Study of Mixed Function Oxidases.— A seasonal study of hepatic microsomal mfo components has been conducted in female R and S fish (submitted for publication). Components studied were cytochromes P-450 and 5, NADPH-cytochrome c reductase, NADPH-dichlorophenolindophenol reductase, NADH-cytochrome c reductase and NADH-cytochrome 5 reductase. All were monitored at 30°C by standard spectrophotometric methods following optimization procedures (8, 9 > 10, n, J 2). Microsomal and total hepatic protein (137 and liver weight to body weight ratios were also monitored. 

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. 

Stanton, R.H. and Khan, M.A.Q. Components of the mixed-function oxidase of hepatic microsomes of fresh water fishes. Gen. Pharmac. (1975) 6, 289-29 +. 

Hepatic microsomal mixed-function oxidase activity of several marine species from coastal Maine. Drug Metab. Dispos. 

Bend, J.R., Pohl, R.J., Davidson, N.P. and Fouts, J.R. Response of hepatic and renal microsomal mixed-function oxidases in the little skate, Ra.ja erinacea, to pretreatment with 3-methyl-cholanthrene or TCDD (2,3,7,8-tetrachlorodibenzo- -dioxin). Bull. Mt, Desert Is. Biol. 

Hepatic microsomal and solubilized mixed-function oxidase systems from the little skate, Baja erinacea, a marine elasmobranch. In Ullrich, V., Hildebrandt, A., Roots, I., Eastabrook, R.W. (Eds.) Microsomes and Drug Oxidations (1976). Pergamon Press, Oxford, pp 16O-I69. 

BENZO(a)PYRENE HYDROXYLASE (AHH) ACTIVITY OF A RECONSTITUTED MIXED-FUNCTION OXIDASE SYSTEM CONTAINING HEPATIC CYTOCHROME P-448 FROM DBA-TREATED MALE SKATES... 

After removal of free Emulgen 913 from partially purified hepatic cytochrome P-448 of DBA-treated male skates an active mixed-function oxidase system was reconstituted by preincubating the cytochrome with purified rabbit hepatic NADPH-cytochrome o... 

Pohl, R. J., Bend, J. R., Guarino, A. M., and Fouts, J. R. Hepatic microsomal mixed-function oxidase activity of several marine species from coastal Maine. Drug Metab. Dispos. (1974) 2 545-555. 

Bend, J. R., Bogar, A., and Foureman, G. L. Partially induced hepatic microsomal mixed-function oxidase systems in individual winter flounder, Pseudoplenroneates ameriaanus, from coastal Maine. Bull. Mt. Desert Island Biol. Lab. (1977) 17 47-49. 

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