• Korean Journal of Pharmacognosy
• /
• v.21 no.1
• /
• pp.74-82
• /
• 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.

• Journal of Nutrition and Health
• /
• v.23 no.1
• /
• pp.11-18
• /
• 1990

Sprague-Dawley male rats were fed the diet of p/s 4.0(soybean oil : I), p/s 0.08(Beef tallow : II) at the level of 15% fat until 8 weeks after weaning. I & II groups were divided into 4 sub-groups by diets with or without 0.3% butylated hydroxytoluene(BHT). 2-AAF was injected at the age of $5_{1/2}$, 6, $5_{1/2}$, 7 weeks. MFO system enzyme(cytochrome p-450, cytochrome p-450 reductase, cytochrome b5) activities and lipid peroxide were determined from isolated liver microsome. 2-AAF injected young rats had growth retardatiion. Lipid peroxide values were not influenced greatly by dietary fat, 2-AAF and BHT. Cytochrome p-450 contents were increased in I-BHT-AAF & II-AAF groups by 2-AAF and its contents were not affected by BHT. But cytochrome p-450 and cytochrome p-450 reductase were not increased in soybean oil diet ybean oil groups. Cytochrome b5 was not influenced by dietary fat, 2-AAF and BHT. Cytochrome p-450 and lipid peroxide, cytochrome p-450 reductase and cytochrome b5, which transfer to MFO system, appeared to have positive correlations(r=0.2474, r=0.2475, p<0.05) each other. This result suggests that MFO system metabolizing 2-AAF was influenced by dietary fats and BHT. 2-AAF induced growth retardation in young rats.

• The Korean Journal of Zoology
• /
• v.27 no.4
• /
• pp.221-230
• /
• 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
• /
• v.40 no.4
• /
• pp.449-455
• /
• 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.

• The Korean Journal of Pesticide Science
• /
• v.7 no.1
• /
• pp.45-50
• /
• 2003

This study was conducted to understand the role of oxidative enzyme cytochrome $P_{450}$ in the bioactivation of benfuracarb and to know metabolites of benfuracarb by cytochrome $P_{450}$. The bimolecular imhibition rate constant $(k_i)$ of benfuracarb on acetylcholinesterase (AChE) was as low as $1.1{\times}10^3\;M^{-1}\;min^{-1}$, suggesting that benfuracarb should be activated for its toxic action. The potency of benfuracarb on AChE in the oxidase system (cytochrome $P_{450}$ + NADPH) in vitro was 10-fold higher than that of control (cytochrome $P_{450}$). Such a similar result was also found in the oxidase + PBO system. In vivo the $I_{50}$ of benfuracarb was 22.7mg $kg^{-1}$, but pie-treatment of piperonyl butoxide (PBO) reduced the $I_{50}$ by >100mg $kg^{-1}$. This result suggests that cytochrome $P_{450}$ was involved in the activation of benfuracarb. Using microsomal oxidase system, metabolites of benfuracarb were elucidated. Fifty-eight percent of benfuracarb was converted to carbofuran, a major toxic metabolite, in the oxidase system, while only less than two percent of benfuracarb was converted to carbofuran in the oxidase + PBO system. These results also suggest that cytochrome $P_{450}$ was involved in the activation of benfuracarb. Overall results indicate that cytochrome $P_{450}$ could be involved in the bioactivation of benfuracarb to carbofuran.

• Korean Journal of Environmental Biology
• /
• v.24 no.2 s.62
• /
• pp.195-200
• /
• 2006

The response of hepatic mixed function oxygenase (MFO) system was investigated in olive flounder exposed to formalin. Hepatic microsome of olive flounder incubated in vitro with formalin demonstrated the induction of cytochrome P450 (CYP), ethoxyresorufin deethylase (EROD), cytochrome P450 reductase (P450R) and cytochrome b5 reductase (b5R) activity. In addition, olive flounder was exposed to 100, 300 and 500 ppm of formalin for 1 h and then transferred to a flow-through type of 1000 L aquarium. Hepatic MFO enzyme activity was determined for 72 h. As the result, hepatic CYP, P450R and EROD activities increased following exposure of formalin, but b5R and GST showed no significant change. These results imply that CYP and P450R can be considered as main hepatic enzymes involving in detoxification of formalin.

• Fisheries and Aquatic Sciences
• /
• v.16 no.4
• /
• pp.261-265
• /
• 2013

The study was conducted to investigate the responses of the hepatic microsomal cytochrome P450 monooxygenase system in the rock bream Oplegnathus fasciatus after chronic exposure to 0, 1, 2, 4, and $8{\mu}g/L$ tributyltin (TBT) concentrations for 4 weeks. Hepatic cytochrome 450 content and ethoxyresorufin O-deethylation (EROD) activity were found to significantly increase in fish treated with the higher concentration of TBT (${\geq}4{\mu}g/L$); however, no significant changes were observed in penthoxyresorufin O-deethylation (PROD) activity in all treated groups compared to the control group. These findings suggest that exposure to a low TBT concentration (${\geq}4{\mu}g/L$) has the potential to induce cytochrome 450 content and EROD enzyme activity in hepatic tissue in the rock bream.

• Korean Journal of Medicinal Crop Science
• /
• v.15 no.6
• /
• pp.437-443
• /
• 2007

This study was carried out to investigate the effect of dietary supplementation with red ginseng water-extracts on the induction of microsomal cytochrome P-450 in rats. Phenobarbital (PB) and 3-methylcholanthrene (3-MC), P-450 inducers, were administered to 3- or 12-month old rats received red ginseng extracts (25 mg/kg) from 6 weeks to 12 months for 3 days. PB and 3-MC increased levels of P-450, P-450 reductase, ethoxycoumarin O-deethylase, benzphetamine N-demethylase and glutathione-S-transferase in the liver of rats. However, chronic administration of red ginseng significantly reduced these increase of enzyme levels induced by P-450 inducers. Chronic administration of red ginseng did not affect the induction of cytochrome $b_5$ and NADH cytochrome $b_5$ reductase by P-450 inducers. It is suggested that the induction of cytochrome P-450 system in the liver in relation to xenobiotics toxicity can be modulated by long-term supplementation with Korean red ginseng to rats.

• Toxicological Research
• /
• v.11 no.2
• /
• pp.205-213
• /
• 1995

This study was undertaken to investigate the effects of organic solvents on xenobiotic metabollzing enzyme system in vivo by meaas of experimental conditions i.e. (1) single group which was treated by benzene (B), toluene (T) and xylene (X), respectively, (2) combination group which was treated by mixture of benzene+toluene (BT), benzene+xylene (BX), and toluene+xylene (TX), respectively, (3) mixture group which was treated by benzene+ toluene+xylene mixture (M), and to interpreat the interaction between the organic solvents metabolizing enzymes. 1. The contents of cytochrome P-450 in liver microsomes were increased (p < 0.01) in organic solvents treated groups, and the contents of cytochrome P-450 were increased by following order of B < T < M < BT=BX < X < TX. 2. The activity of cytochrome P-450 dependent AHHase was significantly higher in organic solvents treated groups than in control group (p < 0.01), and the activity of AHHase was increased by following order of B < T < BT=BX=TX=xylene < M. 3. The activity of NADPH P-450 reductase was significantly higher in organic solvents treated groups than in control group (p < 0.01), and the order of M < combinated group < X < T

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.24 no.6
• /
• pp.859-866
• /
• 1995

This study was done to investigate the effects of chronic ethanol feeding on hepatic microsomal cytochrome system, lipid peroxidation and peroxide metabolizing enzyme activities in 2-acetylaminofluorene(2-AAF) treated rats. Male Sprague-Dawley rats, weighing 120~125g, were pair-fed liquid diets containing 35% of total calories either as ethanol or isocaloric carbohydrates for 6 weeks. After 4 weeks of experimental diet feeding, 2-AAF(100mg/kg body weight) was injected twice a week intraperitoneally. Both weight and percent liver weight per body weight were significantly changed by ethanol feeding. Hepatic microsomal lipid peroxide value and the activities of glutathione(GSH) peroxidase and GSH reductase were not changed by either ethanol or 2-AAF treatment. However the analysis of cytochrome systems showed that both ethanol and 2-AAF increased cytochrome P-450 and bs contents although cytochrome P-450 content was moe affected by 2-AAF while cytochrome b5 content by ethanol. Cytosolic GSH S-transferase activity, which is often elevated during chemical carcinogenesis, also significantly increased by either ethanol feeding or 2-AAF treatment. Overall values for the cytochrome contents and GSH S-transferase activities were highest in 2-AAF treated rats fed ethanol. These results might support the hypothesis that the increase in liver cancer risk associated with chronic ethanol consumption might be due to, at least in part, enhancement of carcinogen bioactivation by ethanol.