Hepatic microsomal cytochrome

Under anaerobic conditions, p,p -DDT is converted to p,p -DDD by reductive dechlorination, a biotransfonnation that occurs postmortem in vertebrate tissues such as liver and muscle and in certain anaerobic microorganisms (Walker and Jefferies 1978). Reductive dechlorination is carried out by reduced iron porphyrins. It is carried out by cytochrome P450 of vertebrate liver microsomes when supplied with NADPH in the absence of oxygen (Walker 1969 Walker and Jefferies 1978). Reductive dechlorination by hepatic microsomal cytochrome P450 can account for the relatively rapid conversion of p,p -DDT to p,p -DDD in avian liver immediately after death, and mirrors the reductive dechlorination of other organochlorine substrates (e.g., CCI4 and halothane) under anaerobic conditions. It is uncertain to what extent, if at all, the reductive dechlorination of DDT occurs in vivo in vertebrates (Walker 1974). 

Costa AK, Katz ID, Ivanetich KM. 1980. Trichloroethylene Its interaction with hepatic microsomal cytochrome P-450 in vitro. Biochem Pharmacol 29 433-439. 

Abou-Donia MB, Lapadula DM, Campbell G, et al. 1985 The synergism of n-hexane-induced neurotoxicity by methyl isobutyl ketone following subchronic (90 days) inhalation in hens Induction of hepatic microsomal cytochrome P-450. Toxicol Appl Pharmacol 81(1) 1-16. 

Hayes JR, Hartgrove RW, Hundley SG, et al. 1975. Interaction of endrin and dieldrin with hepatic microsomal cytochrome 450 from the rat, mouse, and endrin-susceptible and resistant pine voles. Toxicol Appl Pharmacol 32 559-565. 

Chaudhury S, Mehendale HM. 1991. Amplification of carbon tetrachloride toxicity by chlordecone Destruction of rat hepatic microsomal cytochrome P-450 subpopulation. J Toxicol Environ Health 32(3) 277-294. 

Ebel RE. 1980. In vitro effects of chlordecone (Kepone) on hepatic microsomal cytochrome P-450. Pesticide Biochemistry and Physiology 14(3) 221-226. 

Kaminsky LS, Piper LJ, McMartin DN, et al. 1978. Induction of hepatic microsomal cytochrome P-450 by mirex and Kepone. Toxicol Appl Pharmacol 43 327-338. 

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. 

Gigon PL, Gram TE, Gillette JR. 1969. Studies on the rate of reduction of hepatic microsomal cytochrome P-450 by reduced nicotinamide adenine dinucleotide phosphate Effect of drug substrates. Mol Pharmacol 5 109-122. 

Chevion, M., Stegeman, J.J., Peisach, J. and Blumberg, W.E. Electron paramagnetic resonance studies on hepatic microsomal cytochrome P- 50 from a marine teleost fish. Life Sci. (1977) 20, 895-900. 

The influence of phenobarbital on the turnover of hepatic microsomal cytochrome b, and cytochrome P-1+50 in the rat. Biochim. Biophys. Acta (1970) 201, 20-05-... 

An obvious difference was also noted between control and induced skate hepaticdnicrosomal AHH activity in the presence of a-naphthoflavone (10 M). This compound, when added in vitro at this or higher concentrations, caused significant stimulation of AHH activity in control animals (about 3-fold) but inhibition (80%) was found in DBA-pretreated skates. Similar results were earlier reported for control and 3-methylcholanthrene-treated rats (23), where it appears that the response is due to differential effects of a-naphthoflavone on hepatic microsomal cytochrome P-450 (stimulated) and cytochrome P-448 (inhibited) (24). Our data suggests that there may be a novel form of cytochrome P-450 synthesized in skate liver in response to polycyclic hydrocarbon administration, even though there was no hypsochromic shift in the carbon monoxide difference spectrum of dithionite reduced hepatic microsomes from DBA-treated skates (relative to hepatic microsomes from control fish). 

Figure 4. Carbon monoxide difference spectrum of partially purified hepatic microsomal Cytochrome P-448 from DBA-treated little skates. The cuvettes contained dithionite-reduced cytochrome (0.10 mg protein/mL) in lOmM phosphate buffer, pH 7.7, containing 20% glycerol, O.lmM EDTA and O.JtnM dithiothreitol.

Ohmori S, Horie T, Guengerich FP, Kiuchi M, Kitada M (1993b) Purification and characterization of two forms of hepatic microsomal cytochrome P450 from untreated cynomolgus monkeys. Arch Biochem Biophys 305 405 13... 

Wada O et ah Behavior of hepatic microsomal cytochromes after treatment of mice with drugs known to disturb porphyrin metabolism in liver. Biochem Pharmacol 17 595-603, 1968... 

Hexanone has also been shown to potentiate the neurotoxic effects of some compounds. In hens, dermal or inhalation exposure to 2-hexanone in combination with dermal application of the pesticide O-ethyl-O-4-nitrophenyl phenylphosphonothioate (EPN) has resulted in earlier onset and far more severe clinical and histological manifestations of neurotoxic effects than with either chemical exposure alone (Abou-Donia et al. 1985a, 1985b). The authors speculated that this potentiation effect may have been due to induction of hepatic microsomal cytochrome P-450 by EPN, leading to increased metabolism of 2-hexanone to its neurotoxic metabolite, 2,5-hexanedione. An alternate explanation is that local trauma to the nervous tissue produced by 2-hexanone and EPN might increase vascular permeability and thus increase the entry of these compounds and their metabolites from circulation. 

Murray M, Farrell GC. 1984. Different effects of carbon tetrachloride toxicity and cirrhosis on substrate binding to rat hepatic microsomal cytochrome P-450. Biochem Pharmacol 33 687-9. 

There is heterogeneity in human populations for the hepatic microsomal cytochrome P450 enzyme (see Chapter 4). Possession of an unfavorable phenotype may place a patient at risk for drug toxicity. For exam-... 

Wade, A.E., Evans, J.S., Stemson, L.A. Gammans, R.E. (1977) Interaction of nitromethane with reduced hepatic microsomal cytochrome P 450. Biochem. Pharmacol., 26, 963-967 Zitting, A., Nickels, J. Savolainen, H. (1982) Comparison of acute toxic effects of intia-peritoneally injected nitromethane and nitroethane in rats. Toxicol. Lett., 13, 189-194... 

Zang et al [140] reported the liver protective effects of the saponins isolated from A. membranaceus and A. sieversianus against chemical injury induced by CCU, D-galactosamine and acetaminophen in mice. In all cases there were positive activities and the saponins inhibited the rise in SGPT levels, decreased the malondialdehyde (MDA) content and increased the glutathione reduced (GSH) concentration in mouse liver. The same compounds were also evaluated in cultured rat hepatocytes, and the results indicated that the activity may be due to to the antioxidative activity of the saponins, since the content of liver protein in treated mice was more than the control. Moreover, in all treated mice, the level of hepatic microsomal cytochrome P-450 was increased. The liver metabolism and immunoregulating action produced by saponins may be also involved in their hepato-protective effects. Similar results were obtained by Zhang et al [141] when they studied the activity in vitro and... 

Table III. Effects of Dietary Fat and Antioxidants on Hepatic Microsomal Cytochrome Plt5Q Levels in Female Sprague-Dawley Rats...

Marinello AJ, Bansal SK, Paul B, et al. 1984. Metabolism and binding of cylophosphamide and its metabolite acrolein to rat hepatic microsomal cytochrome P-450. Cancer Res 44 4615-4621. 

D. E. Ryan and W. Levin, Pharmacol. Ther., 45,153 (1990). Purification and Characterization of Hepatic Microsomal Cytochrome P-450. 

The metabolism of 1,1-dichloroethane has not been extensively characterized. In vivo studies of the metabolism of 1,1-dichloroethane in humans and animals are very limited. Elucidation of 1,1-dichloroethane s metabolic scheme to date is primarily based on in vitro studies. In general, the identification of specific metabolites and the monitoring of enzyme activities indicate that the biotransformation of 1,1-dichloroethane is mediated by hepatic microsomal cytochrome P-450 system. 

Interferon alfa inhibits several hepatic microsomal cytochrome P4S0 enzymes in vitro and in vivo (SED-13, 1099) (20,413). However, repeated injections of interferon alfa produced conflicting results, with no change in salivary phenazone clearance (SED-13,1099) (414). 

Liu G Effects of some compounds isolated from Chinese medicinal herbs on hepatic microsomal cytochrome P-450 and their potential biological consequences. Drug Metab Rev 23 439H65,1991... 

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