• Archives of Pharmacal Research
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• v.9 no.2
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• pp.81-86
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• 1986

The effect of imperatorin on hepatic microsomal mixed function oxidases (MF0) was investigated. On acute treatment, imperatorin (30 mg/kg, i.p) caused a significant reduction in activities of hepatic aminopyrine N-demethylase, hexobarbital hydroxylase and aniline hydroxylase as well as cytochrome p0450 content in rats and mice. Kinetic studies on rat liver enzymes revealed that imperatorin appeared to be a competitive inhibitor of aminopyrine N-demethylase (Ki,0.007 mM), whereas a non-competitive inhibitor of hexobarbital hydroxylase (Ki, 0.0148 mM). Imperatorin also inhibited non-competitively aniline metabolism (Ki 0.2 mM). Imperatorin binds to phenobarbital-induced cytochrome p-450 to give a typical type 1 binding sepctrum (max. 388nm, min 422 nm). Multiple administrations of imperatorin (30 mg/kg. i. p. daily for 7 days) to mice shortended markedly the duration of hexobarbital narcosis and increased activities of hepatic aminopyrine N-demethylase and hexobarbital hydroxylase and the level of cytochrome p-450 where as aniline hydroxylase activity was unaffected.

• Proceedings of the Ginseng society Conference
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• 1988.08a
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• pp.81-86
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• 1988

The effect of three polyacetylene compounds. panaxydol. panaxynol and panaxytriol isolated from Korean ginseng on $CCI_4-induced$ lipid peroxidation in vitro and in vivo hepatic microsomal lipid peroxidation were investigated. Lipid peroxide levels both in serum and liver and serum enzyme (GOT. GPT. LDH) activities of normal or $CCI_4-treated$ mice and rats were also determined after administration of polyacetylenes. Hepatic microsomal cytochrome P-450 content and activities of aniline hydroxylase and aminopyrine demethylase were measured after treatment of polyacetylenes with or without carbon tetrachloride. As results. treatment with polyacetylenes to control mice did not influence the levels of lipid peroxides and serum enzyme activities while panaxynol did. Panaxynol itself inhibited liver lipid peroxidation in normal mice. Polyacetylene compounds protected hepatic lipid peroxidation and lowered serum lipid peroxide levels induced by $CCI_4$ Polyacetylenes prevented leakage of LDH to serum but elevated GOT and GPT levels caused by $CCI_4$ were not changed by polyacetylene pretreatment. $CCI_4$ caused losses in the content of cytochrome P-450 and activities of aniline hydroxylase and aminopyrine demethylase. When polyacetylenes were treated without $CCI_4$ panaxydol and panaxynol induced aniline hydroxylase and all three polyacetylenes induced aminopyrine demethylase. Cytochrome P-450 contents were not affected by polyacetylenes. In vitro hepatic microsomal lipid peroxidation was inhibited by polyacetylenes and $DL-{\alpha}-tocopherol$ in a concentration-dependent manner.

• The Korean Journal of Zoology
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• v.27 no.4
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• pp.221-230
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• 1984

The activities of aminopyrine demethylase which is marker enzyme of the microsomal drug-metabolizing system, NADPH-cytochrome a reductase and glutathione peroxidase were measured during the course of liver regeneration after about seventy percent hepatectomy in Wistar rats. In addition, the extent of lipid peroxidation and contents of cytochrome P-450 were also measured. Partial hepatectomy produced a significant depression in aminopyrine demethylase, to reach a minium about 24 hours after operation, but this activity was increased to normal value during regeneration. On the other hand, in sham-operated animals, this showed no change. All the activities of NADPH-chrome P-450 contents of liver microsomes were rapidly decreased at the early stage of regeneration. These values returned to normal after 7 days. By contrast, the activity of glutathione peroxidase was nearly unchanged. According to these results, at the early stage of regeneration, the decrease of cytochrome P-450 and NADPH-cytochrome c reductase activity lead to decrease of lipid peroxidation and drug metabolizing enzyme activity. But these phenomena were not detected after 7 days of regeneration.

• YAKHAK HOEJI
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• v.28 no.1
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• pp.53-59
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• 1984

Drug-metabolizing system which has the important role in drug metabolism is localized in smooth endoplasmic reticulum of hepatocytes and is composed of NADPH, NADPH-cytochrome $P_{450}$ reductase, cytochrome $P_{450}$ and others. It is well known that the enzyme system is induced by phenobarbital and methylcholanthrene. Lipid peroxidation is reaction of oxidative deterioration of polyunsaturated lipids. Formation of lipid peroxides in liver microsome has been found to produce degradation of phospholipid, which are major components of microsomal membrane. The relationship between the formation of lipid oxides and the activities of drug-metabolizing enzyme in the liver of rats was reported by several investigators. In this study the effect of riboflavin tetrabutylate, an antioxidant on lipid peroxidation, specially the relationship between lipid peroxidation and drug-metabolizing enzyme system was investigated. In addition the effect of vitamin A derivatives, such as retinoic acid and retinoid on the enzyme was also observed. Results are summarized as followings. 1) The pretretment with riboflavin tetrabutylate inhibited completely the lengthened sleeping time due to $CCl_{4}$ treatment. 2) The increase of TBA value was prevented by the pretreatment with riboflavin tetrabutylate. 3) The pretreatment with riboflavin tetrabutylate also prevented the decrease of drug-metabolizing enzyme caused by $CCl_{4}$. 4) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity.

• YAKHAK HOEJI
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• v.40 no.4
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• pp.449-455
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• 1996

Betaine is one of the major water-soluble components in Lycii Fructus. In the present study the effect of repeated betaine treatment on the hepatotoxicity and the cytochrome P-4 50-dependent enzyme system was examined in adult female rats. Administrations of betaine (100 or 1,000mg/kg/day, ip) to rats repeatedly for 4 or 9 days did not evoke hepatotoxic response as determined by increases in glutamic pyruvic transaminase(GPT) and glutamic oxaloacetic transaminase(GOT) activities measured 24 hours following the final dose of betaine. The activities of aminopyrine N-demethylase, p-nitroanisole O-demethylase and p-nitrophenol hydroxylase as well as the contents of cytochrome P-450 were determined in hepatic microsomes of rats treated with betaine(1,000mg/kg/day, ip) for 4 or 9 days. Repeated treatment of rats with betaine for a period of 4 days induced a marginal decrease in the contents of cytochrome P-450, but did not influence the activities of p-nitrophenol hydroxylase, p-nitroanisole O-demethylase, or aminopyrine N-demethylase. Extension of the betaine treatment to 9 consecutive days failed to alter the parameters for hepatic drug metabolizing activity determined in the present study. Since repeated large doses of betaine were demonstrated to be tolerated by rats without showing any toxicity or changes in drug metabolizing enzyme activities in the liver, this compound appears to be relatively safe to animals upon long-term ingestion.

• Toxicological Research
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• v.12 no.2
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• pp.265-270
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• 1996

Effects of a single administration of dichloromethane (DCM) on the hepatic drug metabollzing activity were determined using adult female rats. Rats were treated with DCM (3 mmol/kg, ip) and the disappearance of antipyrine (100 mg/kg, iv) or ethanol (2 g/kg, ip) from blood was measured. The blood concentration and half-life of antipyrine was not influenced by DCM administration. And DCM did not alter the blood concentration of ethanol measured for 240 min after the treatment. The effect of DCM treatment on in vitro cytochrome P-450-dependent enzyme activities was examined as well. No significant difference in either aniline hydroxylase or aminopyrine N-demethylase was observed in hepatic microsomal fractiorts of rats treated with DCM 24 hr prior to sacrifice. The present study indicates that acutely given DCM does not alter the metabolism of xenobiotics in vivo. The failure of DCM to alter the in vitro hepatic microsomal drug metabolizing activity was also noted.

• Korean Journal of Pharmacognosy
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• v.31 no.2
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• pp.228-234
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• 2000

Effects of Houttuynia cordata on the level of lipid peroxide and the enzyme activities of the liver were investigated in bromobenzene-induced rats. Lipid peroxide content in liver was increased by bromobenzene. It was decreased when the methanol extract from the aerial parts of H. cordata was treated to the rat. The methanol extract reduced the activities of aminopyrine N-demethylase and aniline hydroxylase that increased by bromobenzene, however did not affect glutathione S-transferase activity. The methanol extract recovered the activity of epoxide hydrolase activity that decreased significantly by bromobenzene. We suggest that under our experimental conditions the extract might play an important play in the prevention of hepatotoxicity by reduction of aminopyrine N-demethylase and aniline hydroxylase activities as well as enhancement of epoxide hydrolase activity. Six phenolic compounds have been isolated from H. cordata and identified by means of spectral analysis as protocatechuic acid, quercetin, apigenin, afzelin, hyperoside and quercitrin.

• Journal of Life Science
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• v.13 no.2
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• pp.230-235
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• 2003

To investigate hepatoprotective activities of the root extract of Rosa davurica, the activities of hepatic enzymes, aminopyrine N-demethylase, aniline hydroxylase, glutathione S-transferase and epoxide hydrolase in rats intoxicated with bromobenzene were studied. Pretreatment with the methanol extract from the roots of Rosa davurica did not show any significant effects on the increases of the activities of aminopyrine N-demethylase and aniline hydroxylase, enzymes forming toxic epoxide by bromobenzene. There was no change in glutathione S-transferase activity by Rosa davurica. However, the activity of epoxide hydrolase, and epoxide-removing enzyme, was increased 33% by the administration of 500 mg/kg of the methanol extract. From the results, the protection of Rosa davurica against bromobenzene-induced hepatotoxicity is thought to be via enhancing the activity of epoxide hydrolase, an enzyme removing toxic epoxide rather than through epoxide-producing system.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.141-148
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• 1994

This study was done to determine whether specific alterations exist in hepatic microsomal function after varying periods of ischemia (IS) and reperfusion (RP) during microsomal lipid peroxidation occurs. Rats were pretreated with $\alpha$-tocopherol to inhibit lipid peroxidation or with vehicle (soybean oil). Control animals were time-matched sham-ischemic animals. Four groups of animals were studied: Group 1 (sham), group 2 (30 mins IS), group 3 (60 mins IS) and group 4 (90 mins IS). After 1, 5 or 24 hr of reperfusion, liver microsomes were isolated and cytochrome P-450s were studied. In all vehicle-treated ischemic rats, serum ALT levels peaked at 5 hr and were significantly reduced by $\alpha$-tocopherol pretreatment. Similarly, microsomal lipid peroxidation was elevated in all vehicle-treated ischemic animal groups, but this elevation was prevented by $\alpha$-tocopherol pretreatment. Cytochrome P-450 content was significantly decreased in both group 3 and group 4. In all vehicle-treated ischemic animal groups, aminopyrine N-demethylase activity was significantly decreased for the entire reperfusion period. $\alpha$-Tocopherol inhibited reductions of cytochrome P-450 content and aminopyrine N-demethylase activity at both 1 hr and 5hr of reperfusion but did not affect the reduced levels of cytochrome P-450 content and aminopyrine N-demethylase activity at 24 hr of reperfusion. Aniline p-hydroxylase activity was significantly decreased in group 4, whereas it was increased in group 3. These decreases and increases were prevented by $\alpha$-tocopherol pretreatment. Our finding suggests that abnormalities in microsomal drug metabolizing function occur during hepatic ischemia and reperfusion in vivo and this is attributed to microsomal lipid peroxidation.

• Korean Journal of Food Science and Technology
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• v.32 no.5
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• pp.1179-1185
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• 2000

Fermented anchovy was used to investigate its effects on the formation of lipid peroxide and the activities of epoxide or free radical generating enzyme in vitro in bromobenzene-treated rats. All solvent fractions from fermented anchovy not only showed the strong antioxidative activities on linoleic acid autooxidation, but also reduced bromobenzene-induced hepatic lipid peroxidation. The activities of aniline hydroxylase and aminopyrine N-demethylase elevated by bromobenzene were recovered to the level of normal rats by adding the solvent fractions of fermented anchovy. But, xanthine oxidase and aldehyde oxidase activities were not affected by fermented anchovy. These results suggest that reduction of the bromobenzene-induced hepatic lipid peroxidation is caused by inhibition on the epoxide formation, not on free radical generation.