• 한국식품영양과학회지
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• 제30권2호
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• pp.320-324
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• 2001

To investigate the effect of Sarcodon aspratus methanol extract on liver damage in benzo(a)pyrene (B(a)P)-treated mice, mice were divided into 4 groups of control, B(a)P, Sarcodon aspratus methanol extract and Sarcodon aspratus methanol extract-B(a)P. The activities of serum aminotransferase, cytochrome P-450 and hepatic content of lipid peroxide after B(a)P-treatment were increased than control, but those levels were significantly decreased by the treatment of Sarcodon aspratus methanol extract. On the other hand, the hepatic glutathione content and glutathione S-transferase activity were increased by the treatment of Sarcodon aspratus methanol extract. Also the activities of superoxide dismutase, catalase and glutathione peroxidase were decreased by the treatment of Sarcodon aspratus methanol extract. In addition cytochrome P-450 1A1 isozyme protein level, which was remarkably increased by B(a)P treatment from results of immuno blotting, was decreased by the treatment with methanol extract of Sarcodon aspratus. These results suggest that Sarcodon aspratus methanol extract have protective effect on liver damage by decreasing lipid peroxide and activities of free radical generating enzymes.

• Mass Spectrometry Letters
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• 제3권4호
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• pp.104-107
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• 2012

Mollugin isolated from Rubia cordifolia is known to have anti-inflammatory, anti-cancer, and anti-viral activities. In the present study, a cocktail probe assay and LC-MS/MS were used to investigate the modulating effect of mollugin on cytochrome P450 (CYP) enzymes in male ICR mice. After mollugin was orally administrated to mice at the 20, 40, or 80 mg/kg for 3 days, the activities of CYP in hepatic S-9 fractions were investigated. Unlike the selective inhibitory effect of mollugin on CYP1A2-catalyzed phenacetin O-deethylation in vitro, mollugin only significantly inhibited the activity of CYP2E1-catalyzed chlorzoxazone 6-hydroxylase in vivo. The activities of other CYPs were only slightly altered by mollugin. The results of this study suggest that mollugin might cause herb-drug interactions via the selective inhibition of CYP2E1 in vivo.

• Journal of Microbiology and Biotechnology
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• 제14권5호
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• pp.891-900
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• 2004

UDP-N-Acetylglucosamine(GlcNAc):$\beta$1,4-D-mannoside$\beta$-l ,4N-acetylglucosaminyltransferase-III (GnT-III) and UDP-N-GlcNAc:$\alpha$-6-D-mannosid$\beta$-1,6N-acetylglucosaminyltransferase-V(GnT - V) activities were determined in human hepatoma cell lines and metastatic colon cancer cells, and their activities were compared with those of normal liver cells and fetal hepatocytes. GnT-III activities were higher than those of GnT-V in hepatic carcinoma cells. When the two enzyme activities were assayed in highly metastatic colon cancer cells, GnT - V activities were much higher than those of GnT-III. When GlcN, GlcN-biant-PA and UDP-GlcNAc were used as substrates, the enzymes displayed different kinetic properties between hepatic and colon cancer cells, depending on their metastatic potentials. Normal cells of two origins had characteristically very low levels of GnT-III and -V activities, whereas hepatoma and colon cancer cells contained high levels of activities. These data were supported by RT-PCR and Northern blot analyses, showing that the expression of GnT-III and -V mRNAs were increased in proportion to the enzymatic activities. The increased GnT-III, md -V activities were also correlated with increased glycosylation of the cellular glycoproteins in hepatoma and colon cancer cells, as examined by lectin blotting analysis by using wheat germ glutinin (WGA), erythroagglutinating phytohemagglutinin (E-PHA), leukoagglutinating phytohemagglutinin (L-PHA), and concanavalin A (Con A). Treatment with retinoic acid, a differentiation agent, resulted in decreases of both GnT-III and -V activities of HepG2 and HepG3 cells. In colon carcinoma cells, however, treatment with retinoic acid resulted in a reduction of GnT-V activity, but not with GnT-III activity. Although the mechanism underlying the induction of these mzymes is unclear, oligosaccharides in many glycoproteins have been observed of cancer cells.

• Journal of Microbiology and Biotechnology
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• 제33권10호
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• pp.1351-1360
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• 2023

Endocrine-disrupting chemicals (EDCs) are compounds that disturb hormonal homeostasis by binding to receptors. EDCs are metabolized through hepatic enzymes, causing altered transcriptional activities of hormone receptors, and thus necessitating the exploration of the potential endocrine-disrupting activities of EDC-derived metabolites. Accordingly, we have developed an integrative workflow for evaluating the post-metabolic activity of potential hazardous compounds. The system facilitates the identification of metabolites that exert hormonal disruption through the integrative application of an MS/MS similarity network and predictive biotransformation based on known hepatic enzymatic reactions. As proof-of-concept, the transcriptional activities of 13 chemicals were evaluated by applying the in vitro metabolic module (S9 fraction). Identified among the tested chemicals were three thyroid hormone receptor (THR) agonistic compounds that showed increased transcriptional activities after phase I+II reactions (T3, 309.1 ± 17.3%; DITPA, 30.7 ± 1.8%; GC-1, 160.6 ± 8.6% to the corresponding parents). The metabolic profiles of these three compounds showed common biotransformation patterns, particularly in the phase II reactions (glucuronide conjugation, sulfation, GSH conjugation, and amino acid conjugation). Data-dependent exploration based on molecular network analysis of T3 profiles revealed that lipids and lipid-like molecules were the most enriched biotransformants. The subsequent subnetwork analysis proposed 14 additional features, including T4 in addition to 9 metabolized compounds that were annotated by prediction system based on possible hepatic enzymatic reaction. The other 10 THR agonistic negative compounds showed unique biotransformation patterns according to structural commonality, which corresponded to previous in vivo studies. Our evaluation system demonstrated highly predictive and accurate performance in determining the potential thyroid-disrupting activity of EDC-derived metabolites and for proposing novel biotransformants.

• Animal Bioscience
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• 제36권11호
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• pp.1693-1699
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• 2023

Objective: Cows that are nursing get around 80% of their glucose from liver gluconeogenesis. Propionate, a significant precursor of liver gluconeogenesis, can regulate the key genes involved in hepatic gluconeogenesis expression, but its precise effects on the activity of enzymes have not yet been fully elucidated. Therefore, the aim of this study was to investigate the effects of propionate on the activity, gene expression, and protein abundance of the key enzymes involved in the gluconeogenesis of dairy cow hepatocytes. Methods: The hepatocytes were cultured and treated with various concentrations of sodium propionate (0, 1.25, 2.50, 3.75, and 5.00 mM) for 12 h. Glucose content in the culture media was determined by an enzymatic coloring method. The activities of gluconeogenesis related enzymes were determined by enzyme linked immunosorbent assay kits, and the levels of gene expression and protein abundance of the enzymes were detected by real-time quantitative polymerase chain reaction and Western blot, respectively. Results: Propionate supplementation considerably increased the amount of glucose in the culture medium compared to the control (p<0.05); while there was no discernible difference among the various treatment concentrations (p>0.05). The activities of cytoplasmic phosphoenolpyruvate carboxylase (PEPCK1), mitochondrial phosphoenolpyruvate carboxylase (PEPCK2), pyruvate carboxylase (PC), and glucose-6-phosphatase (G6PC) were increased with the addition of 2.50 and 3.75 mM propionate; the gene expressions and protein abundances of PEPCK1, PEPCK2, PC, and G6PC were increased by 3.75 mM propionate addition. Conclusion: Propionate encouraged glucose synthesis in bovine hepatocytes, and 3.75 mM propionate directly increased the activities, gene expressions and protein abundances of PC, PEPCK1, PEPCK2, and G6PC in bovine hepatocytes, providing a theoretical basis of propionate-regulating gluconeogenesis in bovine hepatocytes.

• 대한방사선기술학회지:방사선기술과학
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• 제23권1호
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• pp.81-89
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• 2000

In the present study, to determine whether the ascorbate protect against radiation damage and the possible relationship among the radioprotective effects and antioxidant actions, the effects of ascorbate(240 mg/kg, i.p) pretreatment of mice on the survival ratio, splenic weight, major antioxidant enzymes(SOD, catalase and glutathione peroxidase) activities, glutathione contents and lipid peroxidation in the liver were examined for 2 weeks after whole-body ${\gamma}-irradiation$(6.5 Gy). The 30-day survival ratio Increased from 10% to 47% for mice treated with ascorbate. The ascorbate decreased the extent of loss in splenic weight and stimulated recovery of splenic weight in irradiated mice(p<0.01). On the day of 14 after ${\gamma-irradiation}$, the ascorbate pretreatment produced a slight increase of antioxidant enzymes activities and significantly increased reduced glutathione(GSH) contents(P<0.05) in the liver compared with non-treated group. Pretreatment with the ascorbate significantly decreased GSSG/total GSH ratio(p<0.05) without the change of GSSG in the liver and inhibited the radiation-induced increase in the hepatic malondialdehyde levels(p<0.05). In these results, we found that its radioprotective effect by protecting antioxidant enzyme activities and glutathione contents from radiation induced a decrease, and thereby suppressing lipid peroxidation which is induced by free radicals.

• 대한의생명과학회지
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• 제10권4호
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• pp.429-434
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• 2004

The effects of intravenous administration of high concentration of taurocholic acid (TCA) on cathepsin B and D, and acid phosphatase activities in rat liver lysosome were studied. These liver lysosomal enzymes were determined from the experimental rats with choledocho-caval shunt (CCS). The activities of liver lysosomal cathepsin B and D, and acid phosphatase were found to be significantly increased in the CCS plus TCA injection group than in control group, such as group of CCS alone group. However, these hepatic enzyme activities did not change in the CCS plus tauroursodeoxycholic acid injection group. The above results suggest that TCA stimulates the biosynthesis of the lysosomal cathepsin B and D, and acid phosphatase in the liver.

• Toxicological Research
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• 제14권2호
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• pp.177-181
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• 1998

Dithiocarbamate and mixed disulfide containing allyl functions were designed and synthesized as putative chemopreventive agents, i.e. N,N-diallyldithiocarbamate (DATC) and S-(N,N-diallyldithiocarbamoyl)-N-acetylcysteine (AC-DATC). DATC and AC-DATC were administered and the activities of cytosolic glutathione S-transferase (GST), glutathione reductase (GR) and microsomal N-nitrosodiethylamine (NDEA) deethylase were assayed in order to test the effects of these organosulfur com-pounds on the detoxification and metabolic activation system of NDEA. The amounts of hepatic glutathione (GSH and GSSG) was also determined. The administration of DATC to rats led to an increase in the activity of GR and to an inhibition of CYP2E1-mediated NDEA deethylation. AC-DATC induced the activity of GR and GST, increased the hepatic GSH content and inhibited the rate of NDEA deethylation. The level of GSSG was decreased as a consequence of the increased activity of GR. These effects may contribute to possible antimutagenic and anticarcinogenic action of the dithiocarbamates investigated.

• Archives of Pharmacal Research
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• 제18권3호
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• pp.189-194
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• 1995

The focus of this study was to investigate the influences of enzymatic scavengers of active oxygen metabolites and phospholipase $A_2$ inhibitor on hepatic secretory and microsomal function during hepatic ischemia/reperfusion. Rats were pretreated with free radical scavengers such as superoxide dismutase (SOD), catalase, deferoxamine and phospholipase $A_2$ inhibitor such as quinacrine and then subjected to 60 min. no-flow hepatic ischemia in vivo. After 1, 5 hr of reperfusion, bile was collected, blood was obtained from the abdominal aorta, and liver microsomes were isolated. Serum aminotransferase (ALT) level was increased at 1 hr and peaked at 5 hr. The increase in ALT was significantly attenuated by SOD plus catalase, deferoxamine and quinacrine especially at 5 hr of reperfusion. The wet weight-to-dry weight ratio of the liver was significantly increased by ischemia/reperfusion. SOD and catalase treatment minimized the increase in this ratio. Hepatic lipid peroxidiltion was elevated by ischemia/reperfusion, and this elevation was inhibited by free radical scavengers and quina crine. Bile flow and cholate output, but not bilirubin output, were markedly decreased by ischemia/reperfusion and quinacrine restored the secretion. Cytochrome $P_{450}$ content was decreased by ischemia/reperfusion and restored by free radical scavengers and quinacrine to the level of that of the sham operated group. Aminopyrine N-demethylase activity was decreased and aniline p-hydroxylase was increased by ischemia/reperfusion. The changes in the activities of the two enzymes were prevented by free radical scavengers and quinacrine. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory functions as well as microsomal drug metabolizing systems by increasing lipid peroxidation, and in addition to free radicals, other factors such as phospholipase $A_2$ are involved in pathogenes of hepatic dysfunction after ischemia/reperfusion.

• Journal of Pharmaceutical Investigation
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• 제9권4호
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• pp.23-28
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• 1979

The effect of maltitol admininstration to rat was studied on breakdown of ${\alpha}-glycoside$ linkage with intestinal mucosa or pancreatic enzymes and induction of hepatic polyol dehydrogenase activities. Maltitol was contained as 13% or 26% in diet, and was administrated to rat for 9 weeks. This report carried out that ${\alpha}-glycoside$ linkage of maltitol was not hydrolyzed with pancreatic enzymes and intestinal mucosa. Maltitol dehydrogenase was not obeserved in liver cytoplasm, and hepbtic sorbitol dehydrogenase was not induced by maltitol administsation. Also, the effect of maltitol on aging of aluminum hydroxide gel, prepared by the reaction of aluminum chloride solution with strong ammonia solution to final pH 7.0, was studied by potentiometric titration, pH and acid-consuming capacity. Gel containing 1% or 2% maltitol was lost less than 2% of their acid-consuming capacity during a 120 days aging period compared with a loss of more than for an identical gel without maltitol and gel containing 0.5% maltitol.