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At least 19 recordsLinked to original sources
PubMed1989

Influence of spices and spice principles on hepatic mixed function oxygenase system in rats.

The status of hepatic mixed function oxygenase system (MFOS) was investigated in rats fed spice principles: capsaicin, piperine and curcumin, as well as spices: cumin, ginger, fenugreek, cinnamon, asafoetida, mustard and tamarind at two dietary levels each. Liver microsomal cytochrome P450-dependent aryl hydroxylase was generally stimulated by these spice principles and spices. Cumin, ginger and fenugreek also stimulated the levels of cytochrome P450 and cytochrome b5 and cumin and tamarind stimulated N-demethylase activity. NADPH-cytochrome c reductase and glucuronyl transferase activities, however, remained unaffected by the spices tested.

Animals↗
PubMedDate not supplied

Differential effects of Walker 256 carcinosarcoma cells growing subcutaneously, intramuscularly, or intraperitoneally on hepatic microsomal mixed-function oxygenase activity.

Walker 256 rat carcinosarcoma cells growing as solid subcutaneous or intramuscular tumors depressed hepatic microsomal mixed-function oxygenase activity to less than 20% of control activity, but the same tumor cells growing as free ascites cells in the peritoneal cavity did not. Necrosis of the core area of solid tumors was observed. Tumor cells may release a substance that depresses hepatic microsomal mixed-function oxygenase activity only upon their death.

Animals↗
PubMed1982

Responsiveness of Carmustine (BCNU) treated mice to induction and inhibition of mixed function oxygenases.

The responsiveness of BCNU treated mice to phenobarbital (Pb) induction of hepatic microsomal mixed function oxygenase (MFO) activity was studied. BCNU (30 mg/kg ip) produced significant (P less than 0.05) decreases in cytochrome P-450, total ethylmorphine metabolism (TEM) and ethylmorphine N-demethylase (EMN) by 21 days after treatment. The specific activities of TEM and EMN were decreased more than was P-450 content. Benzpyrene hydroxylase (BPH) was increased and 7-ethoxycoumarin 0-deethylase (ECD) was unaffected at this time. Pb induction beginning on day 17 after BCNU treatment resulted in a greater inductive response in the BCNU treated mice than in controls. The specific activities of all MFO enzymes studied were more markedly affected than were the raw activities suggesting activation. However, the responsiveness of the MFOs to the actions of inhibitory was not markedly influenced by BCNU pretreatment.

Animals↗
PubMed1977

A comparative study on the influence of cysteamine and metyrapone on mixed-function oxygenase activities in variously pretreated liver microsomes from rats and mice.

It has been found that metyrapone can inhibit both type I and type II mixed-function oxygenase reactions, while cysteamine inhibits only type I activity in this mammalian system. Following pretreatment with phenobarbital and 3-methylcholanthrene the half-maximal inhibiting concentrations for the O-demethylation of paranitranisol are increased for cysteamine and decreased for metyrapone. Both cysteamine and metyrapone give type II binding spectra with oxidized cytochrome P-450. The negative and positive peaks are at 393 and 426 nm respectively for metyrapone, and 410 and 434 nm for cysteamine. Cysteamine showed no binding comparable to that of metyrapone for reduced cytochrome P-450. Metyrapone showed little or no inhibition of the NADH cytochrome-c reductase (EC 1.6.1.1) or NADPH (EC 1.6.2.3) cytochrome-c reductase while cysteamine had a more or less strong inhibiting effect depending on the pretreatment of animals. Neither the binding to P-450 heme nor the inhibition of NADH and NADPH cytochrome-c reductase correlates well with cysteamine inhibition of total activity. It is therefore suggested that cysteamine reacts with an intermediate electron carrier of non-heme iron or glycoprotein character thus inhibiting mixed-function oxygenase activity.

Acetanilides↗
PubMed1981

Metabolism of alphaxalone in the rat: evidence for the limitation of the anaesthetic effect by the rate of degradation through the hepatic mixed function oxygenase system.

The rates of degradation of the steroid anaesthetic alphaxalone (3 alpha-OH-5 alpha pregnane-11,20 dione) have been studied in vitro using isolated hepatocyte and microsome preparations. Evidence is presented that alphaxalone is metabolized rapidly by the hepatic mixed function oxygenase system. Induction of cytochrome P450 in vivo leads to an increase in the maximum rate of degradation of alphaxalone in both in vitro systems. Induction of cytochrome P450 caused a decrease in the duration of the anaesthetic affect in vivo of a limiting dose of Althesin (alphaxalone/alphadolone acetate). It is concluded that, under certain conditions, the duration of the anaesthetic effect of alphaxalone is determined by the rate of metabolism of this compound by the mixed function oxygenase system of the liver.

Alfaxalone Alfadolone Mixture↗
PubMed1995

Seasonal responses of the mixed-function oxygenase system in the American oyster, Crassostrea virginica (Gmelin 1791), to urban-derived polycyclic aromatic hydrocarbons.

Mixed-function oxygenase (MFO) system components (cytochrome P450 and b5, "423 peak" and NADPH cytochrome c reductase) and body burdens of polycyclic aromatic hydrocarbons (PAHs) were determined seasonally in oysters, Crassostrea virginica (Gmelin 1791), collected from an undeveloped estuary (North Inlet, SC) and an urbanized estuary (Murrells Inlet, SC). All MFO system components monitored in oysters from North Inlet demonstrated seasonal variations; levels were lowest during October 1992. Whole oyster PAH tissue levels were always higher in Murrells Inlet oysters compared with North Inlet oysters. Seasonal variation of PAH body burdens was evident in oysters from Murrells Inlet; the highest levels occurred during April 1993. Differences between the two estuaries were seasonally evident in most oyster MFO system components. Reductase activity was highest at the most contaminated Murrells Inlet site during October 1992 and April 1993. This seasonal variation was positively correlated to that of their PAH body burdens. Cytochrome P450 content was also elevated at the most contaminated site during April 1993. These results suggest that reductase activity and cytochrome P450 content in Murrells Inlet oysters were induced by the high PAH body burdens during April 1993 and indicate their potential as molecular biomarkers of PAH contamination.

Animals↗
PubMed1989

Characterization of the microsomal mixed-function oxygenase system of the hepatopancreas and green gland of the red swamp crayfish, Procambarus clarkii.

1. The microsomal mixed-function oxygenase (MFO) system from the hepatopancreas and green gland of the red swamp crayfish, Procambarus clarkii has been characterized with respect to the constitution of electron transport proteins and the ability to catalyze the metabolism of xenobiotics. 2. Cytochrome P-450 content of hepatopancreas microsomes was approximately 10-fold higher than that of green gland and comparable to that of rat liver. NADPH-cytochrome c reductase activity in hepatopancreas microsomes was approximately 2% of that found in rat liver microsomes. 3. Green gland microsomes catalyzed higher turnover rates of aminopyrine N-demethylase and benzo[a]pyrene hydroxylase than hepatopancreas microsomes. With hepatopancreas microsomes, organic hydroperoxides supported a greater rate of aminopyrine N-demethylation than did NADPH plus O2. 4. P. clarkii hepatopancreas microsomes generally displayed a lower binding affinity (Ks) for a number of type I and type II ligands than did rat liver microsomes.

Animals↗
PubMed1984

Selectivity of mixed-function oxygenase enzyme induction in flounder (Pseudopleuronectes americanus) collected at the site of the Baie Verte, Newfoundland oil spill.

A marked level of mixed-function oxygenase (MFO) enzyme induction was observed in kidney but not in liver tissues of winter flounder collected at the site of a spill of No. 2 fuel oil in Newfoundland. A number of MFO-linked, electron transport components including cytochrome P450, cytochrome P450 reductase and cytochrome b5 reductase were also slightly elevated in kidney tissues of fish at the oiled site. The results obtained in this particular field trial demonstrate that reliance on the measurement of liver MFO parameters alone could lead to false negatives in biological monitoring programs. The study also indicates that the exclusive use of liver tissues to investigate the induction potential of various chemicals should be avoided.

Animals↗
PubMed1985

In vivo protection by protein A of hepatic microsomal mixed function oxygenase system of cyclophosphamide-treated rats.

At a high dose, cyclophosphamide (Cy, 200 mg/kg) causes depression of the enzyme activity of the hepatic mixed function oxygenase (MFO) system in Sprague-Dawley rats. The present report provides evidence for the early regeneration of the depleted enzyme activity in Cy-treated rats by purified protein A (P) of Staphylococcus aureus. Enzymes of the MFO system, such as aminopyrine demethylase and aryl hydrocarbon hydroxylase, were assayed and the content of cytochrome P-450 was determined. Inoculation of P (60 micrograms/kg) prior to Cy inoculation provides a better effect than P administration after Cy. The exact mechanism of P action is unknown. P-treated animals appear to have an ability to repair the damage caused by the toxic metabolites of Cy earlier than those in the Cy group. This property of protein A may become useful in accelerated regeneration of the enzyme activity in the hepatic MFO system following the toxic insult of Cy metabolites.

Animals↗
PubMed1996

Measuring the potency of pulp mill effluents for induction of hepatic mixed-function oxygenase activity in fish.

A bioassay protocol was optimized for measuring the potency of effluents or waterborne chemicals for inducing mixed-function oxygenase (MFO) activity of rainbow trout (Oncorhynchus mykiss). Measurements of ethoxyresorufin O-deethylase (EROD) can be made with an established endpoint assay using large volumes of reagents and tissue. However, a new kinetic microplate assay offers significant savings in time, reagents, and sample volumes. Data are distributed lognormally and must be log transformed before statistical analyses. EROD activity increases with exposure time to pulp mill effluent, and a 4-d exposure provides a near-maximal response. Optimum fish size conforms to standard practices in fish toxicology; loading rates should not exceed 1 g of fish per liter of test solution per day. Feed should be withheld from test fish 48 h before testing to reduce the variance of measured activity, and anaesthetizing fish with MS-222 does not affect their response to MFO inducers. Pulp mill effluents do not lose their potency during 2-3 wk of exposure at temperatures ranging from -20 to 13 degrees C, whether stored in plastic or glass. Steel containers were associated with slight losses in potency. Bioassays of MFO induction in fish exposed to liquid effluents are practical and conform to standard practice for testing the lethality of waterbone chemicals. The results are sufficiently precise that differences among means based on live fish per treatment can be discriminated statistically when activity changes by threefold or more.

Analysis of Variance↗
PubMed1976

Modifications of drug metabolism by disulfiram and diethyldithiocarbamate. I. Mixed-function oxygenase.

Disulfiram and diethyldithiocarbamate were administered to rats for 4 days alone (300 mg/kg, daily, per os) or in combination with phenobarbital (80 mg/kg, daily, i.p.), in order to observe the effects of these compounds on the microsomal membrane components and on the mixed-function oxygenase system. Both disulfiram and diethyldithiocarbamate increased the liver to body weight ratio, and the total hepatic protein content. Disulfiram significantly increased also the microsomal protein and phospholipid contents. Diethyldithiocarbamate and disulfiram partially prevented the increase of microsomal protein and phospholipid contents caused by phenobarbital. Disulfiram and diethyldithiocarbamate decreased the amount of cytochrome P-450 and P-420, and the activity of p-nitroanisole O-demethylase. These changes were more pronounced after diethyldithiocarbamate than after disulfiram treatment. On the contrary, the activity of NADPH-cytochrome c reductase was enhanced only by disulfiram. The induction by phenobarbital of cytochrome P-450 and p-nitrosanisole O-demethylase was partially prevented on concomitant treatment with disulfiram and diethyldithiocarbamate. These compounds. however, had an additive effect with phenobarbital in enhancing the microsomal NADPH-cytochrome c reductase activity.

Animals↗
PubMed1998

Antibiotic effects on cytochromes P450 content and mixed-function oxygenase (MFO) activities in the American alligator, Alligator mississippiensis.

There are no Food and Drug Administration (FDA)-approved antimicrobial agents for use in cultured American alligators (Alligator mississippiensis) destined for human consumption yet some producers administer antibiotics for prophylaxis. The cytochromes P450-dependent mixed-function oxygenases (MFO) catalyze the oxidation of xenobiotic compounds such as drugs, pesticides and polycyclic aromatic hydrocarbons. Herein, we describe the effects of oxytetracycline, ceftazidime and enrofloxacin on the MFO system of the American alligator, Alligator mississippiensis. Juvenile alligators (4 animals/treatment) were administered these antibiotics intraperitoneally in an effort to induce hepatic microsomal cytochromes P450. Alligators treated with enrofloxacin exhibited emesis and convulsive spasms within 5 min of the initial injection. Total hepatic cytochromes P450 contents were significantly decreased in oxytetracycline-and enrofloxacin-pretreated alligators. In vitro hepatic microsomal benzyloxyresorufin O-dealkylase (BROD) activity was significantly decreased by enrofloxacin pretreatment. Western blots of proteins from antibiotic-pretreated alligator hepatic microsomes incubated with several mammalian and fish cytochromes P450 (CYP) antibodies exhibited little or no induction of CYP1A1, 2B, 2C and 2E1. In vitro incubation with enrofloxacin and oxytetracycline caused a concentration-dependent decrease in alkyl-substituted phenoxazone dealkylase activities catalyzed by phenobarbital- and 3-methylcholanthrene-induced alligator hepatic microsomes.

Alligators and Crocodiles↗
PubMed1982

Effects of phenobarbital and sodium salicylate on cytochrome P-450 mixed function oxygenase and glutathione S-transferase activities in rat brain.

The effects of acute and therapeutic doses of phenobarbital and sodium salicylate on cytochrome P-450 mixed function oxygenase (EC 1.14.14.1) and glutathione S-transferase (EC 2.5.1.18) activities have been studied in rat brain and compared with those of rat liver. P-450 enzymic activity was assayed by N-demethylation of p-chloro-N-methylaniline and 1-chloro-2,4-dinitrobenzene was used as substrate for glutathione S-transferase activity. The acute effects of a single daily dose of phenobarbital (75 mg/kg/day; i.p.) and sodium salicylate (500 mg/kg/day; i.p.) for 3 days increased cytochrome P-450 as well as glutathione S-transferase in rat liver. But the same doses of both drugs decreased glutathione S-transferase levels in rat brain and increased cytochrome P-450 dependent N-demethylation of p-chloro-N-methylaniline. The therapeutic doses of sodium salicylate (50 mg/kg/day; i.p.) and phenobarbital (10 mg/kg/day; i.p.) daily for 21 days increased cytochrome P-450 in rat liver as well as in brain. The increase in brain glutathione S-transferase by prolonged treatment of phenobarbital was significant compared to the control values.

Animals↗
PubMed1983

Destruction of hepatic mixed-function oxygenase parameters by CCl4 in rats following acute treatment with chlordecone, Mirex, and phenobarbital.

Previous work has established the marked potentiation of CCl4 hepatoxicity by prior exposure to chlordecone (CD). This study was conducted to determine if prior exposure to CD results in enhancement of CCl4-induced destruction of the hepatic microsomal mixed-function oxygenase (MFO) system. Male Sprague-Dawley rats received a single oral dose of CD (10 mg/kg) or corn oil vehicle alone (1 ml/kg) 24 hr prior to a single ip injection of CCl4 (0-100 microliter/kg). Mirex (M; 10 mg/kg) and phenobarbital (PB; 80 mg/kg/day for two days) were used as negative and positive controls respectively for the potentiation of CCl4 hepatotoxicity. Hepatotoxicity was evaluated 24 hrs after CCl4 administration by elevations of three serum enzymes (GPT, GOT, and ICD). The key hepatic microsomal MFO parameters measured were microsomal protein, cytochrome P-450 content, glucose-6-phosphatase (G-6-Pase), and aminopyrine demethylase (APD). As previously demonstrated using a subchronic dietary pretreatment protocol, CD potentiated CCl4 hepatotoxicity over a range of CCl4 doses to a greater extent than PB or M, as judged by elevations in serum enzymes. PB caused the greatest increase in total P-450 content and the greatest increase in CCl4-mediated destruction of microsomal protein and APD activity. M caused the least destruction of total hepatic cytochrome P-450, despite the same level of cytochrome P-450 as in the PB group. CD treatment caused the greatest decrease in G-6-Pase activity in comparison to PB or M pretreatments and a similar degree of P-450 destruction as observed with the PB group. These findings suggest that in general, CCl4-induced destruction of hepatic MFO parameters measured in this study is disproportional to the known degree of potentiated hepatotoxicity by the pretreatments and does not accurately reflect the potentiation of CCl4 hepatotoxicity by CD.

Alanine Transaminase↗
PubMed1975

Aryl hydrocarbon (benzo[a]pyrene) hydroxylase: a mixed-function oxygenase in mouse skin.

Mouse skin contains aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity which is inducible by aromatic polycyclic hydrocarbons and benzoflavones. The duration and magnitude of induction, but not the initial kinetics, are dependent on the inducer dose. The cutaneous hydroxylase activity is inhibited by carbon monoxide and requires the presence of NADPH, indicating that the enzyme is one of the mixed-function oxygenases. The highest enzyme activity was found in the superficial layer of skin which contains the sebaceous glands and the upper pilary canals. Enzyme activities were intermediate in the epidermis and lowest in the deeper dermal layers.

Animals↗
PubMed1991

Responses of mixed-function oxygenase and antioxidase enzyme system of Mytilus sp. to organic pollution.

1. Mixed-function oxidase (MFO) system components (cytochrome P-450, "418-peak", cytochrome b5 and NADPH-cytochrome c(P-450) reductase) and inducible antioxidant enzymes (catalase, superoxide dismutase (SOD), glutathione peroxidase (GPX) and DT-diaphorase) has been determined in digestive glands of mussels (Mytilus galloprovincialis) collected from three Mediterranean coastal locations, exhibiting an organic pollution gradient. 2. Cytochrome P-450, the "418-peak", catalase and SOD showed a good correlation with whole body tissue PAHs and, to a lower extent, with PCBs. 3. Microsomal NADPH-dependent DT-diaphorase, but not the NADH-dependent microsomal enzyme or the cytosolic DT-diaphorases, was indicated to increase with pollution exposure. 4. The application of such measurements to environmental monitoring is discussed. Given the magnitude of differences observed, and the state of knowledge on enzyme function and mechanisms of toxicity, a multiparameter approach is considered to offer current and future potential for detecting the impact of organic pollution on bivalve molluscs.

Animals↗
PubMed1987

Review and perspective on the use of mixed-function oxygenase enzymes in biological monitoring.

It is often suggested that changes in simple biochemical/physiological responses may be useful for predicting the impacts of pollutants at population and community levels of biological organization. There are serious conceptual constraints to such a thesis and its seems likely that such simple responses can go no further than serving as early warning systems for delineating potential areas of pollutant impact--areas which (if shown to be significant in size) can then be subjected to more detailed population and community type studies. Environmental testing is a prerequisite for any response suggested to have value as a biological monitoring index and the induction of mixed-function oxygenase (MFO) enzymes has now been validated in a large number of field studies worldwide. Investigations have progressed from documenting induction near localized sources of hydrocarbon contamination to more diffuse sources of mixed organic pollution originating from industrial and domestic sources. Studies in the Great Lakes and Europe have demonstrated that the induction of MFO enzymes is a biological response of sufficient sensitivity to discriminate water quality differences over broad geographical areas. We suggest that as an early warning system, the induction of these enzymes can fulfill the requirement of "most sensitive biological response" for assessing a variety of organic pollution conditions. Given the high level of sensitivity of the MFO enzyme response, negative as well as positive field trials can be of value in addressing concerns about the toxicological significance of "high-profile" chemicals (and potent inducers) such as polycyclic aromatic hydrocarbons and organochlorines. MFO enzyme induction can also be an economical tool for environmental managers for reacting to real or perceived concerns about pollution such as effects on commercial fish stocks at sites of petroleum hydrocarbon development in the oceans.

Animals↗