Microsomal monooxygenases activity

Walker, C.H. (1978). Species differences in microsomal monooxygenase activities and their relationship to biological half lives. Drug Metabolism Reviews 7(2), 295-323. 

Vodicnik, M.J., C.R. Elcombe, and J.J. Lech. 1981. The effect of various types of inducing agents on hepatic microsomal monooxygenase activity in rainbow trout. Toxicol. Appl. Pharmacol. 59 364-374. 

Fingerlings were injected ip with 14C-labeled PCB mixture at 0.3,1,3,10, and 30 mg PCB/kg BW tissues sampled up to 70 days postinjection At 3 days postinjection high doses of 10 and 30 mg PCB/kg BW caused elevation of liver microsomal monooxygenase activity when maximum tissue concentrations, in mg total PCB/kg FW, were 55 in bile, 12 in blood, 8 in muscle, and 8 in liver. Elevated hepatic microsomal monooxygenase activity with muscle and liver PCB concentrations of >0.3 mg/kg FW, but not 0.25 mg/kg FW 6... 

Melancon, M.J., K.A. Tumquist, and J.J. Lech. 1989. Relation of hepatic microsomal monooxygenase activity to tissue PCBs in rainbow trout (Salmo gairdneri) injected with [14C] PCBs. Environ. Toxicol. Chem. 8 777-782. 

Oikari, A. and B. Jimenez. 1992. Effects of hepatotoxicants on the induction of microsomal monooxygenase activity in sunfish liver by beta-naphthoflavone and benzo[a]pyrene. Ecotoxicol. Environ. Safety 23 89-102. 

Starek A. 1988. [The effect of kerosene hydrocarbons on microsomal monooxygenases activity in rat liver.] Folia Med Cracov 29(3-4) 161-170. (Polish)... 

Evans, J.G, Appleby, E.C., Lake, B.G Coiming, D M. (1989) Studies on the induction of cholangiofibrosis by coumarin in the rat. Toxicology, 55, 207-224 Faurschou, P. (1982) Toxic hepatitis due to benzo-pyrone. Hum. Toxicol, 1, 149-150 Fentem, J.H. Fry, J.R. (1991) Comparison of the effects of inducers of cytochrome P450 on Mongolian gerbil and rat hepatic microsomal monooxygenase activities. Xenobiotica, 21, 895-904... 

Irreversible inhibition, which is much more important toxicologically, can arise from various causes. In most cases the formation of covalent or other stable bonds or the disruption of the enzyme structure is involved. In these cases the effect cannot be readily reversed in vitro by either dialysis or dilution. The formation of stable inhibitory complexes may involve the prior formation of a reactive intermediate that then interacts with the enzyme. An excellent example of this type of inhibition is the effect of the insecticide synergist piperonyl butoxide (Figure 9.6) on hepatic microsomal monooxygenase activity. This methylenedioxyphenyl compound can form a stable inhibitory complex that blocks CO binding to P450 and also prevents substrate oxidation. This complex results from the formation of a reactive intermediate, which is shown by the fact that the type of inhibition changes from competitive to irreversible as metabolism, in the... 

It is apparent from extensive reviews of the induction of monooxygenase activity by xenobiotics that many compounds other than methylenedioxyphenyl compounds have the same effect. It may be that any synergist that functions by inhibiting microsomal monooxygenase activity could also induce this activity on longer exposure, resulting in a biphasic curve as described previously for methylenedioxyphenyl compounds. This curve has been demonstrated for NIA 16824 (2-methylpropyl-2-propynyl phenylphosphonate) and WL 19255 (5,6-dichloro-l,2,3-benzothiadiazole), although the results were less marked with R05-8019 [2,(2,4,5-trichlorophenyl)-propynyl ether] and MGK 264 [A-(2-ethylhexyl)-5-norbomene-2,3-dicarboximide],... 

Acetanilide 4-hydroxylase (A4H) is a microsomal monooxygenase activity that can be followed by means of the model substrate acetanilide. In the HPLC assay developed for this activity, the conversion of acetanilide to 4-hydroxyacetanilide was followed. 

Among the phase I reactions, oxidation mediated by cytochrome P450 monooxygenases is the most important in insects. Resistance to insecticides caused by enhanced microsomal monooxygenase activities has been reported in numerous insects. 

Hepatic microsomal monooxygenase activity was also studied in several marine species from coastal Maine (Pohl et al., 1974). Table 9.2 shows that microsomal monooxygenase activities varied widely in these species, even though the taxonomic gap is smaller than that shown in Table 9.1. 

Figure 9.1 Relative liver microsomal monooxygenase activities in different species, adjusted for liver/body weight ratios. (From Walker, C.H., Drug Metab. Rev., 7, 295,1978. With permission.)...

Age effects in drug metabolism are illustrated in Figure 9.3, showing how the rabbit liver microsomes increase in activity with age. In this species, the level of microsomal monooxygenase activity in adults is reached in about 30 days. 

Dietary a-pinene causes southern armyworm larvae to become more tolerant to the botanical insecticide, nicotine. Enhanced tolerance to synthetic insecticides also has been demonstrated in phytophagous insects fed plants capable of inducing microsomal monooxygenase activity. Variegated cutworm larvae fed peppermint leaves are more tolerant of the insecticides carbaryl, acephate, methomyl, and malathion than larvae fed snap bean leaves. Increased tolerance for carbaryl and methomyl also has been observed in larvae of the cabbage looper and alfalfa looper (Autographa califomica) fed peppermint plants instead of their favored host plants, broccoli and alfalfa. 

In addition, important detoxification enzymes such as cytochrome P450 monooxygenases and glutathione S-transferases can be used as biomarkers for monitoring pesticide pollution. For example, Jensen et al. (1991) showed that treatment of rainbow trout (Onco-rhynchus mykiss) with endosulfan (as low as 8.3 ppb) induced two microsomal monooxygenase activities (7-ethoxyresorifin O-demethylase and aldrin epoxidase). Martinez-Lara et al. (1996) found that dieldrin and malathion induced individual isozymes of GST in the gilthread seabream, Sparus aurata. 

Brady JF, Xiao F, Gapac JM, et al. 1990. Alteration of rat liver microsomal monooxygenase activities by gasoline treatment. Arch Toxicol 64 677-679. 

TABLE 1 Selective induction of liver microsomal monooxygenase activities by benzo [a] pyrene... 

Poland A, Mak I, Glover E, et al. 1,4-/Rv[2-(3,5-dichloropyridyloxy)]benzene, a potent phenobarbital-like inducer of microsomal monooxygenase activity. Mol Pharmacol 1980 18 571-80. 

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