• 생약학회지
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• 제21권1호
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• pp.74-82
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• 1990

The effects of naturally occurring furanocoumarins on cytochrome P-450 have been investigated in rat liver microsomes. Incubation of microsomes with an NADPH-generating system and four furanocoumarins such as imperatorin, isoimperatorin, phellopterin and byakangelicin at $37^{\circ}$ in vitro resulted in a significant destruction of cytochrome P-450. A single treatment(50 mg/kg, i.p.) of rats with each furanocoumarin caused a rapid loss of cytochrome P-450 accompanied by the loss of heme from the microsomes but not by the loss of cytochrome $b_5$. It is suggested that cytochrome P-450 is specifically destroyed by furanocoumarins in a metabolic process involving destruction of its heme group and as a consequence, hepatic enzyme activities are depressed markedly.

• BMB Reports
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• 제32권3호
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• pp.226-231
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• 1999

In vitro effects of acetone on cytochrome P450 (P450)-dependent benzo(a)pyrene (B(a)P) hydroxylation supported by cumene hydroperoxide (CuOOH) or NADPH/$O_2 $ systems were studied using 3-methylcholanthrene-pretreated rat liver microsomes. The maximal rate of B(a)P hydroxylation at constant concentration ($80\;{\mu}M)$ of the substrate was observed in the presence of $30\;{\mu}M$ CuOOH. However, at concentrations higher than $30\;{\mu}M$ CuOOH the hydroxylation rates were rapidly decreased. In contrast to CuOOH, at a concentration of $200\;{\mu}M$ NADPH, B(a)P hydroxylation rate reached a plateau. At concentrations higher than $200\;{\mu}M$ NADPH, the rates of substrate hydroxylation were maintained at the maximal rate with no inhibition. Acetone at 1% (v/v) enhanced both CuOOH- and NADPH/$O_2$-supported B(a)P hydroxylation at the optimal concentrations of the cofactors. At concentrations higher than 1% (v/v) acetone, substrate hydroxylation was sterero specific under the support of these two cofactors; it was strongly enhanced with $30\;{\mu}M$ CuOOH, but rather inhibited in the $200\;{\mu}M$> NADPH/$0_2 $ system. The lipid peroxidation rate induced during CuOOH-supported P450-dependent B(a)P hydroxylation was increased as CuOOH concentrations were increased. Acetone in the concentration range of 2.5~7.5%(v/v) inhibited lipid peroxidation during CuOOH supported B(a)P hydroxylation. The finding that CuOOH-supported B(a)P hydroxylation is greatly enhanced by acetone suggests that acetone may contribute more to the activation of oxygen (for the insertion of oxygen into the substrate) in the presence of CuOOH than with NADPH/$O_2$. Acetone may also contribute to the partial inhibition of destruction of microsomal membranes by lipid peroxidation.

• 약학회지
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• 제22권4호
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• pp.175-192
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• 1978

Chlorination of the polluted water may produce odoriferous and objectionable-tasting chlorophenols which are hazardous to health. These studies were undertaken to investigate the hazardous effects of chlorophenols to the rat. 1. The chlorophenols such as o-chlorophenol and 2,6-dichlorophenol inhibited rat growth and caused increment of the ratio between liver weight and body weight. 2. The hemoglobin content, hamatocrit ratio and A/G of rat blood were decreased by chlorophenols administration. The activities of alkaline phosphatase, lactic dehydrogenase (LDH) and glutamate oxaloacetate transaminase (GOT) in serum as well as in liver were increased provisonally and decreased after one or two weeks adminstration. 3. The liver mitochondrial respiration ($QO_{2}$) was inhibited by chlorophenols treatment in in-vivo and in-vitro test. 4. The liver microsomal cytochrome P-450 was decreased by chlorophenols administration 5. Liver tissue was degenerated with congestion, atrophy, swelling, vacuolation, dilation of rough endoplasmic reticulum and denature of mitochondrial particle with swelling, and cristal destruction by chlorophenols adminstration. 6. After one and two weeks of adminstration of chlorophenols to rat, the aberrations of bone marrow chromosome and inhibition of its mitosis were observed respectively.