• Biomedical Science Letters
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• v.12 no.2
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• pp.91-97
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• 2006

The effects of intravenous administration of high concentration of taurocholic acid (TCA) on monoamine oxidase (MAO) A and B activities in rat liver mitochondria and microsomes were studied. These liver subcellular organelles and serum MAO activities were determined from the experimental rats with choledocho-caval shunt (CCS). The Michaelis-Menten constants in these hepatic enzymes were also measured. The activities of mitochondrial MAO A and B, and microsomal MAO B as well as their $V_{max}$ values were found to be decreased significantly in CCS plus TCA injected group then in the control group, such as CCS alone groups. However their $K_m$ values in the experimental groups did not vary. MAO of serum appeared in the CCS plus TCA injected groups only. The above results suggest that TCA represses biosynthesis of the MAO in the liver. The MAO of serum is believed to be caused by the increment of membrane permeability of hepatocytes upon TCA mediated liver cell necrosis.

• The Korean Journal of Food And Nutrition
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• v.10 no.1
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• pp.37-43
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• 1997

This study was undertaken to evaluate as antioxidant activity against lipid peroxidation. Silymarin and silybin extracted from Silybum marianum were successively purified wit solvent fractionation by silica gel column chromatography. These isoflavonoid inhibited superoxide anion production in the xanthine oxidase system. In the rat liver microsomes, silymarin or silybin rapidly inhibited lipid peroxidation which was initiated enzymatically by reduced nicotinamide adenine dinucleotide phosphate(NADPH) or non-enzymatically by ascorbic acid or Fenton's reagent (H2O2+Fe2+). Mitochondrial lipid peroxidation was also inhibited by silymarin and silybin. silymarin and silybin inhibited on terminating radical chain reaction during lipid peroxidation in the enzymatic system of microsomes or in the linoleic acid hydroperoxide induced peroxidation system.

• Archives of Pharmacal Research
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• v.26 no.10
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• pp.800-804
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• 2003

The effects of KR-31378, a neuroprotective agent for ischemia-reperfusion damage, on liver microsomal cytochrome P450s (CYPs) were investigated in male Sprague Dawley rats. When rats were treated orally with KR-31378 for 7 consecutive days, CYP3A-selective erythromycin N-demethylase (ERDM) activity was significantly induced in a dose-dependent manner. In Western immunoblotting, CYP 3A proteins were clearly induced by treatment with KR-31378. Within 24 h after treatment with 80 mg/kg of KR-31378, ERDM activity was induced in liver microsomes in accompanied by induction of the level of CYP 3A proteins. The present results suggest that KR-31378 might modulate the expression of CYP 3A enzymes in humans.

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.209-216
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• 2001

The purpose of the present study was to investigate the hepatic uptake and biliary excretion of l-anilino-8-naphthalene sulfonate (ANS) in vivo. The plasma concentration and liver concentration of ANS were determined after its i.v. bolus administration at a dose of $30\;{\mu}mol/kg$ in rats. The hepatic uptake clearance $(CL_{uptake})$ of ANS was 0.1 ml/min/g liver. On the basis of the unbound concentration of ANS, the permeability-surface area product $(PS_{influx})$ was calculated to be l0.4 ml/min/g liver, being comparable of in vitro data. On the other hand, we determined the plasma concentration, liver concentration and biliary excretion rate of ANS at steady-state after its i. v. infusion $(0.2-1.6\;{\mu}mol/min/kg)$ in rats. The excretion clearance $(CL_{excretion})$ of ANS showed Michaelis-Menten kinetics with increasing the infusion rate. The permeability-surface area product $(PS_{excretion})$ based on the unbound concentration in the liver was calculated to be 0.0165 ml/min/g liver, which is negligible compared with the intrinsic clearance $(CL_{int}=3.3\;ml/min/g\;liver)$ by rat liver microsomes. The sequestration process of ANS, therefore, was considered to be mainly due to the metabolic process in the liver $(PS_{seq}{\risingdotseq}CL_{int})$. Furthermore, $PS_{efflux}$ value calculated from $PS_{influx}$ and $PS_{seq}$ was 4.4 ml/min/g liver, which was comparable of in vitro data. In conclusion, in vivo parameters such as $PS_{influx}$, $PS_{efflux}$ and $PS_{seq}$ in the present study showed good in vivo-in vitro relationship. Thus, the kinetic analysis method proposed in the present study would be useful to analyze the hepatic transport of drugs in vivo.

• Environmental Analysis Health and Toxicology
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• v.16 no.2
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• pp.97-102
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• 2001

The flavin-containing monooxygenases(FMOs) (EC1.14.13.8) are NADPH0dependent flavoenzymes that catalyze oxidation of soft nucleophilic heteroatom centers in a range of structurally diverse compounds, including foods, drugs, pesticides, and other xenobiotics. In humans, FMO3 is quantitatively a major human liver monooxygenase. In the present study, the baculovirus expression vector system was used to overexpress human FMO3 in sect cells for stalytic studies. Microsomes isolated from Spodoptera frugiperda(Sf)9 cells infected with human FMO3 recombinant baculovirus catalyzed the NADPH-and O$_2$-dependent oxidation of methimazole, thiourea, and phenylthiourea. However there was no detectable activity with 1, 3-diphenylthiourea or larger thiocarbamides. Microsomes from control Sf9 cells were devoid of methimazole or thiourea S-oxygenase activity. 1, 3-diphenylthiourea is apparently completely excluded from the catalytic site, these amines drugs are probably approaching the upper size limits of xenobiotics accepted by human FMO3. The substrate specificity of this iosform in humans appears considerably more restriceted than that of pig, guinea pig, rat or rabbit FMO3.

• Journal of Nutrition and Health
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• v.36 no.4
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• pp.376-381
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• 2003

Acyl-CoA synthetase 4 (ACS4) is an arachidonate-preferring enzyme abundant in steroidogenic tissues. We examined ACS4 in rat liver, which contains a variety of pathways that use acyl-CoAs, in order to determine subcellular locations. We demonstrate that ACS4 protein was present most abundantly in the mitochondria and to a much lesser extent in the peroxisomes and microsomes. To determined the dietary effects on the level of ACS4 mRNA, northern blotting was carried out using total RNA from the livers of adult male rats fed various diets. Fasting, high fat diet, and fat-free high sucrose diet increased the hepatic level of ACS4 mRNA approximately 2-fold. Furthermore, the levels of ACS4 mRNA were induced by DEHP[Di- (2-ethylhexyl) phthalate]. These data suggest that ACS4 expression in the liver is regulated with a variety of pathways, including $\beta$-oxidation, hormone, and insulin.

• Archives of Pharmacal Research
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• v.26 no.7
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• pp.535-539
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• 2003

The EtOAc soluble fraction from the stem of Sorghum bicolor showed a strong free radical scavenging activity. Five major compounds were isolated from this fraction. They were identified by spectral data as methyl ferulate (1), methyl p-hydroxycinnamate (2), p-hydroxybenzaldehyde (3), tricin (4), and quercetin 3,4 -dimethyl ether (5). Among these compounds, 1 exhibited a strong, free radical scavenging activity on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) with an $IC_50$ value of 0.7 $\mu$M. We further studied the effects of these isolated compounds on the lipid peroxidation in rat liver microsomes induced by non-enzymatic method. All five compounds showed anti-lipid peroxidation activity ($IC_50$ values of 0.5, 0.4, 0.3 and 0.3 $\mu$ M, respectively).

• BMB Reports
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• v.30 no.2
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• pp.157-161
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• 1997

The present paper reports characteristics and specificity of the inhibitory action of $N^{\alpha}-tosyl-L-lysine-chloromethyl\;ketone$ (TLCK) and $N^{\alpha}-tosyl-L-phenylalanine-chloromethyl\;ketone$ (TPCK) on the glucose6-phosphate transporter of rat liver microsomes. The TLCK-induced inhibition was pH dependent. The inhibition constants for TPCK were determined by following pseudo-Lst order reaction mechanism. The inhibition was protected by preincubation with excess amount of glucose-6-phosphate. The results proved that (a) TLCK inactivates the microsomal glucose-6-phosphate transporter, (b) the inhibition results from the modification of sulfhydryl groups of the transporter.

• Journal of Microbiology and Biotechnology
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• v.10 no.2
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• pp.233-237
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• 2000

As part of a continuing investigation to identify free radical scavengers from the fruit bodies of basidiomycetes, we isolated two p-terphenyl compounds, designated as PAl and PA2l, from cethanolic extract of the fruit body of Pasillus panuoides. The methanolic extract was processed by ethyl acetate extraction and silica gel column chromatography to yield two active fraction. PAl was obtained from one of the fractions through Sephadex LH-20 and silica gel column chromatographies and reverse-phase HPLC. The other fraction was purified by Sephadex LH-20 and reverse-phase column chromatographies to produce PA2. The compounds PA1 and PA2 were identified as leucomentin-4 and leucomentin-2, respectively, on the basis of various spectroscopic analyses. These compounds exhibited strong inhibitory activities against lipid peroxidation in rat liver microsomes with IC_{50}$ values of 0.10 and $0.06{\;}\mu\textrm{g}ml$, respectively.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.127.2-128
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• 2003

Rutaecarpine is an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa. In addition to its traditional use in treatment of gastrointestinal disorders, rutaecarpine has recently been characterized to have anti-inflammatory activity through cyclooxygenase-2 inhibition. More recently, to develop rutaecarpine as an anti-inflammatory agent, total synthesis of rutaecarpine has successfully been established in our group. (omitted)