Nak Eung Sung | 14 Articles |
[English]
To evaluate the effect of BHA and BHT on liver tissue, BHA and BHT, 100mg and 200mg/kg B.W. respectively, were given to experimental animals for 4 months. Microsomal cytochrome P-450, cytochrome b5, cytochrome C reductase activity and lipid peroxidation of liver tissue of experimental animal were measured. The results were as follow ; 1) Cytochrome P-450 increased significantly in experimental group given BHA but cytochrome b5 did not. 2) Cytochrome oxidnse activity increased moderately in BHA group but decreased in BHT group. From these finding, it can be assumed, that BHA and BHT has no great effect on human tissue. Citations Citations to this article as recorded by
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The effect of intraperitonelly administered higenamine on the cytochrome P -450, b5, P-nitroanisole-O-demethylase and lipid peroxidation in the rat hepatic microsomes were determined. The following results were obtained ; 1) The intraperitonelly administered higenamine increased contents of rat hepatic microsomal cytochrome P-450 and b5. 2) The principal role of cytochrome P-450 in mixed function oxidase reactions includes hydroxylation of various drugs, fatty acids, steroids, pesticides and carcinogens. The increased cytochrome P-450 induced by higenamine decreased on the both AAF of N-hydorxylation and Ring-hydroxylation. 3) Activity of P-nitroanisole-O-demethylase in hepatic microsomes with higenamine was decreased accorting to incresed dosage of higenamine. 4) The formation of lipid peroxides was increased according to increased dosage of higenamine.
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Lipoprotein cholesterol and triglyceride levels have been determined innormal and diabetes. The abnormalities of lipoprotein were investigated by SDS-polyacrylamide gel electrophoresis in the serum and the 3 major lipoprotein classes for diabetes. HDL cholesterol levels were lower in the diabetes compared to the normals. VLDL triglyceride levels also elevated in the diabetes. There were significant shifts in the distribution of lipoprotein cholesterol, with an increase in LDL cholesterol and decrease in HDL cholesterol. The results of this study suggest that diabetes may be associated with changes in both lipoprotein triglyceride and cholesterol levels. The electrohoretic patterns of VLDL and HDL in diabetes showed the abnormal pattern in comparison to normal.
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[English]
Ethanol enhances the activity of microsomal enzyme system and lipid peroxidation. We observed the effect of chronic ethanol administration on cytochrome P-450 level and lipid peroxidation in rat liver microsome. The results were as follows : 1) When rats were administered with ethanol, the level of microsomal cytochrome P-450 was decreased and lipid peroxidation did not change significantly. 2) When vitamin A and E were added incubation medium in each group, lipid per-oxidation was decreased significantly. Citations Citations to this article as recorded by
[English]
Rabbit adrenocrtical mitochondria contains cytochrome P-450 dependent hydrox-ylase system, capable of catalyzing the hydroxylation as well as other modifications of variety of lipids and foreign compounds, including drugs, pesticides, carcino-gens. Ethanol enhances the activity of the microsomal enzyme system, and cold exposure increases various enzyme activity. The present study investigated the effects of chronic ethanol administration and cold exposure on rabbit adrenocortical mitochondria 11β-and 18-hydroxylase activity, cytochrome P-450 and b5 and AAF hydroxylation, serum cortisol level and lipid content of the adrenal cortex. The results obtained are : 1) When rabbits were administrated with 15% and 30% ethanol and were exp-osed to cold, the level of adrenocortical mitochondrial 11 β-hydroxylase activity was increased, but 18-hydroxylase activity was slightly increased only in the cold exposure group. This result corresponded with an increase of serum cortisol level. 2) When rabbits were administrated with ethanol and were exposed to cold, the level of cytochrome P-450 in adrenocortical mitochondria was increased, but cytochrome b5 level did not change. Ring-hydroxylation of AAF did not change, but N-hydroxylation was increased. 3) When rabbits were administrated with ethanol and were exposed to cold, the levels of total cholesterol and triglyceride in adrenal cortex was remarkably incre-ased, but phospholipid level was reduced.
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We observed the effect of the administration of vitamin A,C and E with β-naphthoflavone and piperonyl butoxide on cytochrome P-450 level and lipid peroxidation in rats liver. The level of hepatic cytochrome P-450 decreased after vitamin A,C and E was administration. In contrast, β-naphthoflavone, when administered with vitamin A,C and E, the increase of cytochrome P-450 was prevented. Lipid peroxidation was decreased after vitamin A, C, and E was administered. Moreover when β-naphthoflavone was administered together with vitamin A, C and E lipid peroxidation was not increased. When piperonyl butoxide was administered together with vitamin A,C and E, both cytochrome P-450 and lipid peroxidation were decreased. These results indicate that vitamin antioxidants can prevent lipid peroxidation by a cytochrome P-450 dependent terminal oxidase system in rat liver microsomes.
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The cytochrome enzyme system of hepatic microsomes is important because of its versatility, being capable of catalysing the hydroxylation as well as other modifications of variety of lipids and foreign compounds, including drugs, pesticides, carcinogens, and anesthetics. In order to elucidate the effect of various anesthetics on hepatic microsomal cytochrom P-450, b5, and AAF hydroxylation and, on the hepatic lipid contents, inhalation anesthetics, including diethyl ether, halothane, enflurane, and intravenouse anesthetics, including ketamine, thiopental, innovar were administered to albino rats either ones or thrice with the following conclusions: 1. Various anesthetics utilized in the present investigation increase the activities of hepatic microsomal cytochrome P-450 and b5, with concomitant elevation of AAF hydroxylation in hepatic microsomes. 2. The aove various anesthetics increase the cholesterol and triglyceride contents of liver. 3. The above various anesthetics do not make an influence of the phospholipid content of liver. 4. Variations in the cytochromal enzyme activity of hepatic microsomes have no correlations with variations in the lipid contents of liver by the administration of various anesthetics, while correlations in the contents of hepatic triglyceride and cholesterol have statistically significant correlation with each other by the administration of them.
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The principal role of cytochrome P-450 in many other mixed function oxidase reactions including hydroxylations or oxidative dealkylations of various drugs, fatty acids, steroids, pesticides, and carcinogens. In order to elucidate the effect of various vitamin antioxidants on hepatic microsomal cytochrome P-450 and AAF hydroxylation, vitamin antioxidants, including vitamiin A acetate, L-ascorbic acid and DL-α-tocopherol were administered to rats. The results of this study show that the inhibition of cytochrome P-450 level and AAF hydroxylation by vitamin antioxidants may be related to their ability to prevent the in vivo activation of AAF to carcinogenic N-hydroxylation. Vitamin antioxidants, because of their effectiveness in inhibiting chemical carcinogenesis, may become useful chemoprophylatic agents against environmental carcinogens.
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We have investigated in rat liver whether different forms of cytochrome P-450 are alterated in hepatic disorders associated with impaired drug metabolism. Total hepatic cytochrome P-450 is decreased after either bile duct ligation or the administration of estradiol. In contrast, phenobarbital administrated alone increase hepatic content of cytochrome P-450, and when administrated with estradiol the reduction in cytochrome P-450 was prevented. Four forms of microsomal cytochrome P-450 apoproteins, ranging in molecular weight from 50 000 to 58,000, were tentatively identified in a sodium dodecyl sulfate(SDS)-6M urea polyaocrylamide gel electrophoresis system. Phenobrbital administration icreased primarily band IV(50,000 daltons). Bile duct ilgation was associated with a marked reduction in bands II and III while bands II and III were decreased with estradiol benzoate administration. Sumultaneous administration of phenobarbital and estradiol demonstrated a return of band I and an increase in density of bands III and IV. Simultaneous administration of cholic acid and estradiol demonstrated a return of band I and not altered in band III and IV. These studies support the hypothesis that multiple forms of cytochrome P-450 are present in liver microsomal membranes and that alterations in spenific apoproteins may be associated with an increase or a decrease in the functional properties of cytochrome P-450.
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The effects of vitamin B complexes on both ring and N-hydroxylation of 2-ace-tylaminofluorene by rat hepatic microsomal fraction were studied. In the presence of thiamine-Hcl during incubation, the total hydroxy-AAF was increased by 50.3%. 0.1mM and 1.0mM riboflavin inhibited only total hydroxy-AAF with 56.7% and 85.0 whereas N-hydroxy AAF was increased to some extent. 1.0mM niacin did not have much effect on the total hydroxy-AAF, but 0.1mM niacin decreased the total dydroxy-AAF by 28.6%. Presence of p-amino-benzoic acid, calcium pantothenate, pyridoxal-Hcl or vitamin B12 inhibited the total hydroxy-AAF to some extent. But the radio of ring-and N-AAF hydroxylation was not changed by these vitaminn B complexes. Our present results suggest that vitamin B complexes were not effective in vitro metabolism of 2-AAF to N-hydroxy AAF(activation step of AAF) by a cytochrome p-450 dependent mixed function oxidase system.
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We have investigated the effect of administation of exogenous cholic acid whether total hepatic cytochrome P-450 and b5 are altered in the bile duct-ligated rats. The effect of administration of exogenous cholic acid on the hepatic microsomal mixed-fuction oxidase system is various according to the administration route, dosage and date after administration. In normal rats, 1ml of 0.5m mol cholic acid solution per 100g body weight administrated intravenously increases hepatic content of cytochrome P-450 and b5 on the third to fifth days after injection. Total hepatic cytochrome P-450 and b5 are decreased after either bile duct ligation or the administration of ethinyl estradiol. In contrast when cholic acid is adminstrated simultaneously with bile duct ligation, the reduction in cytochome P-450 is relativery prevented. These effects are similar to the potential of phenobarbital for reversing the bile duct ligation-associated decrease in all components of the mixed function oxidase system.
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Male Wistar rats maintained for a period of 6 weeks on a basal vitamin E-deficiency diet consisting of 70% sucrose, 20% vatamin-free casein, 4% tocopherol, stripped lard, 4% salt mixture, and 2% tocopherol-free vitamin fortification mixture were used to compare two sets of commonly used salt mixture(salt mixture USP XIV versus Briggs' salt mixture). Among the rats maintained on the deficient diets for 6 weeks, only that received the combination of Briggs' salt mixture showed a significantly lower level of hepatic catalase activity, cytochrome P-450, and b5 compared to the corresponding control animals. Since the most striking differences in these diets are in their contest of iron, it appears that these two dietary constituents may intact in modulating the effect of vitamin E on hepatic hemoproteins.
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Our studies are concerned with cytochrome P-450 content and 2-acetylaminofluorene N-and ring-hydroxylation by thiamine deficient rat liver microsomes. Incubation medium contained 100mM HEPES buffer pH 7.8, 2mM NADPH, 100mM KF, 100nM [14C]-AAF and microsomal protein. After 30min, incubation at 37℃, ring and N-hydroxy-9-14C-AAF formations are assayed by radioactivity measurements after paper chromatography separation. The concentration of cytochrome P-450 is elevated in microsomes from rats fed the deficient diet. It appears that the thiamine deficient rat liver is capable of producing effects on the drug hydroxylation enzymes.
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