Cytochrome 3-methylcholanthrene effect

In vitro inhibition of rat liver microsomal aniline hydroxylase by methylcholanthrene effect on microsomal cytochromes P-450 and bs, and NADPH cytochrome c reductase studied 490... 

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). 

An approach for determining the presence of multiple monooxygenases in rat liver microsomes was the use of chemicals that selectively affected certain monooxygenase activities but not others. For example, 7,8-benzoflavone (a-naphthoflavonc) markedly inhibited the hydroxylationofbenzo[a]pyrene by liver microsomes from 3-methylcholanthrene treated rats or by a cytochrome P448-dependent reconstituted enzyme system (68,69), but there was no effect or only a small stimulatory effect of 7,8-benzoflavone on benzo[a]pyrene metabolism in livers from untreated rats (68). 

Yasoshima M, Masuda Y. 1988. Effects of carbon disulfide on liver microsomal cytochrome p-450 in phenobarbitol and 3-methylcholanthrene-induced animals. Jpn J Pharmacol 46 ... 

The potential of tricyclohexyltins to modify the inducibility of cytochrome P450 by various substances, such as 3-methylcholanthrene, is of considerable toxicological importance. Significant metabolic interactions can result from a combination of environmental chemicals and drugs that produce alterations in heme and mixed function oxygenase activity, suggesting that more research is needed on interaction effects of organotins with other environmental substances or contaminants. 

There are three general differences between the inductive effects of phenobarbital and 3-methylcholanthrene (1) 3-methylcholanthrene produces a more selective stimulation of hepatic enzymes. i.e., increases the metabolism of fewer substrates (2) 3-methylcholanthrene increases the amount of cytochrome P-4S0 but does not alter the amount of NADPH cytochrome c reductase (3) the delay between exposure and maximum enzyme induction is of the order of hours for 3-methylcholanthrene and days for phenobarbital (Fig. 6). 

A stimulus which alters the steady-state level of an endogenous cellular component may do so by influencing its rate of synthesis, its rate of break-down, or both. When administered to intact animals, phenobarbital or 3-methylcholanthrene increase (20-50%) the steady-state level of microsomal protein. Similarly, micro-somes from animals pretreated with phenobarbital or 3-methylcholanthrene incorporate radioactive amino acids into protein more rapidly than microsomes from control animals and this effect is blocked by co-administration of actinomycin-D. It was therefore assumed that the increased levels of microsomal protein and enzyme activity after inducers were the result of enhanced synthesis. However, turnover studies have revealed that phenobarbital in particular has a profound effect upon microsomal protein catabolism. Proteins of the endoplasmic reticulum were labelled by injection of radioactive amino acids and the rate at which radioactivity disappeared from the microsomes was compared in control and phenobarbital-treated animals. Assuming a comparable degree of isotope re-utilization in the two groups, this approach provides a relative measure of microsomal-protein turnover. In control animals, radioactivity of total microsomal protein decreases with time with a half-time of about 3 days. In phenobarbital-treated animals, however, there is a marked stabilization of microsomal protein so that almost no radioactivity is lost over a S-day period. The reduced protein catabolism is observed both in total microsomes and in a purified microsomal protein, NADPH cytochrome c reductase. Thus, repeated administration of phenobarbital to animals evokes an increase in... 

Mushrooms have been consumed as flavorful and medicinal foods for millenniums. Mushroom polysaccharides possess antitumor activity through the stimulation of cytokine productions from immunocytes. On the other hand, lipopolysaccharide suppresses the expression of various hepatic cytochrome P450s (CYPs) through the production of cytokines such as tumor necrosis factor (TNF)-a. In this study, lentinan prepared from Lentinus edodes and polysaccharides from Agaricus blazei (ABPS) were intraperitoneally injected to female BALB/c mice, and the effects of these polysaccharides on the expression of CYPs were investigated in the liver. Both polysaccharides down-regulated the activity and level of constitutive and 3-methylcholanthrene-inducible CYPIA accompanied by the TNF-a production. When... 

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