• BMB Reports
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• v.51 no.9
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• pp.474-479
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• 2018

Cisplatin is one of the most effective chemotherapeutic drugs used in the treatment of HCC, but many patients will ultimately relapse with cisplatin-resistant disease. Used in combination with cisplatin, resveratrol has synergistic effect of increasing chemosensitivity of cisplatin in various cancer cells. However, the mechanisms of resveratrol enhancing cisplatin-induced toxicity have not been well characterized. Our study showed that resveratrol enhances cisplatin toxicity in human hepatoma cells via an apoptosis-dependent mechanism. Further studies reveal that resveratrol decreases the absorption of glutamine and glutathione content by reducing the expression of glutamine transporter ASCT2. Flow cytometric analyses demonstrate that resveratrol and cisplatin combined treatment leads to a significant increase in ROS production compared to resveratrol or cisplatin treated hepatoma cells alone. Phosphorylated H2AX (${\gamma}H2AX$) foci assay demonstrate that both resveratrol and cisplatin treatment result in a significant increase of ${\gamma}H2AX$ foci in hepatoma cells, and the resveratrol and cisplatin combined treatment results in much more ${\gamma}H2AX$ foci formation than either resveratrol or cisplatin treatment alone. Furthermore, our studies show that over-expression of ASCT2 can attenuate cisplatin-induced ROS production, ${\gamma}H2AX$ foci formation and apoptosis in human hepatoma cells. Collectively, our studies suggest resveratrol may sensitize human hepatoma cells to cisplatin chemotherapy via gluta${\gamma}H2AX$mine metabolism inhibition.

• Journal of Food Hygiene and Safety
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• v.14 no.4
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• pp.415-421
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• 1999

The flavin-containing monooxygenases (FMOs) (EC 1.14. 13.8) are NADPH-dependent 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, FMOl appears to be the predominant form expressed in human fetal liver. cDNA-expressed human FMO and human liver microsomal FMO have been observed to N- and S-oxy-genate nucleophilic nitrogen- and sulfur-containing drugs and chemicals, respectively. In the present study, FMOl can be expressed in the baculovirus expression vector system at level of 2.68 nmol FMOl/mg of membrane protein. This isoform was examined for its capacity to metabolize methimazole to its S-oxide using thiocholine assay. Kinetic studies of its S-oxide by recombinant human FMO1 result in Km of 7.66 $\mu$M and Vmax of 17.79 nmol/min/mg protein.

• Archives of Pharmacal Research
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• v.21 no.1
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• pp.35-40
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• 1998

Human cytochrome P450 4F2 shows high regioselectivity in hydroxylation of stearic acid and leukotriene $ B_4.$ As a first step of its regulation study, human cytochrome P450 4F2 genomic DNA was isolated from liver of a person who was administered clofibrate for 10 years. From Southern hybridization, restriction enzyme digestion and sequencing experiments, isolated genomic DNA fragment was found to contain around 32 Kb DNA and more than 20 Kb of $5^I$ end regulatory region. Sequences of the structural gene region revealed exon 1 and exon 2. Further regulation studies would elucidate the feedback mechanisms of the oxidative degradation of fatty acids, inflammatory response and the clearance of leukotriene B4 in the liver. Furthermore, regulation study of this gene could explain the species difference in responses to peroxisome proliferator and help in the safety evaluation of peroxisome proliferating chemicals to human being.

• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.143-146
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• 2011

Scutellariae Radix is widely used in the traditional herbal medicine for the treatment of fever, cough, dysentery, hepatitis and hypertension in Korea, China and Japan. In this study, we investigated the effects of 70% ethanolic extract of Scutellariae Radix (SRE) on CYP450-mediated drug metabolism in the in vitro systems using human liver microsomes and hepatocytes. The microsomal incubation assay showed that SRE inhibited the drug metabolism reactions catalyzed by CYP1A2, CYP2C8 and CYP2C9 in a dose-dependent manner. In particular, SRE was shown to strongly inhibit the metabolic activity of CYP1A2 with an $IC_{50}$ value of 4.6 ${\mu}g/mL$. When SRE was evaluated for its effect on the induction of CYP450 enzyme activities in cryopreserved human hepatocytes, SRE did not exhibit any effect.

• Advances in Traditional Medicine
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• v.3 no.1
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• pp.18-20
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• 2003

The purpose of this study was to examine the effect of supplementary highly purified chitosan (HPC) on blood alcohol concentration in healthy human. The human study was performed with two sections. Each section of the study was conducted by two-phase cross-over design with a week wash-out period. All volunteers took HPC in one phase, and took a placebo in the next phase. Blood alcohol concentrations were different between in those taking HPC and in those taking the placebo in the human. And the concentration of serum aspartate aminotransferase (AST, GOT) and alanine aminotransferase (ALT, GPT), the indicator of liver cell damage, was lowered in those taking HPC, compared to those taking the placebo. In conclusion, taking HPC prior to drinking alcohol can somewhat reduce alcohol concentration in human blood and liver cell damage.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.140.1-140.1
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• 2003

Permanent cell culture lines derived from human cancer tissue are important experimental models in the study of human cancer cell proliferation. The in vitro effects of C. militaris and its extracted fractions on the human breast cancer (SK-BR3), liver cancer (SK-Hep1, HepG2), kidney cancer (p15), lymphoma (Jurkat) were studied. F1 (CCCA, crude cordycepin containing adenosine), F2 (ethanol precipitation), F3 (ethanol soluble supernatant) and F4 (fraction of through SK-1B) significantly stimulated in vitro cytotoxic in human cancer cell lines. (omitted)

• Mass Spectrometry Letters
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• v.12 no.4
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• pp.172-178
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• 2021

HYIpro-3-1 is an adjuvant for preventing or treating inflammatory growth diseases. In this study, we identified the metabolic pathway of HYIpro-3-1 in human liver microsomes (HLMs) by quadrupole-orbitrap high-resolution mass spectrometry (HR-MS) and characterized the major human cytochrome P450 (CYP). Ten metabolites were identified, including one O-demethylation (M1), two O-demethylation and monohydroxylation (M2 and M3), and seven monohydroxylation metabolites (M4-M10). Based on the HR-MS² spectra, the metabolites are divided into two groups of monohydroxylated metabolites according to the hydroxylation position. We verified that HYIpro-3-1 is metabolized by CYP in HLMs, CYP2B6 is mainly involved in O-demethylation, and various CYPs are involved in the monohydroxylation of HYIpro-3-1.

• Journal of Yeungnam Medical Science
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• v.18 no.1
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• pp.1-12
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• 2001

Liver transplantation is widely accepted as an effective therapeutic modality for a variety of irreversible acute and chronic liver diseases for which no satisfactory therapy is available. Following the first unsuccessful efforts at human liver transplantation in 1963, development of the procedure evolved at first slowly and steadily for 20 years and then rapidly over the past two decades. The growth of liver transplantation was facilitated by the conclusion of the national institutes of health consensus development conference in 1983 that liver transplantation is not an experimental procedure but an effective therapy that deserves broader application. The number of liver transplantations increased 2.4-fold(from 1.713 to 4.058) from 1988 to 1996. but the number of patients on the UNOS(united network of organ sharing) liver list increased 12.1-fold(from 616 to 7,467); as would be expected, the number of deaths of listed patients increased 4.9-fold(from 195 to 954), The current supply of donor livers is insufficient to meet this need, and organ donation has been stagnant or increased by only a few percent in recent years. These facts underscore the importance of the appropriate selection of candidates for liver transplantation and the development of operative procedures, such as living donor liver transplant, split liver transplant and auxiliary partial liver transplant.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.196-196
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• 2001

Stereoselective metabolism and inhibitory potential of lansoprazole enantiomers were evaluated from the incubational studies of human liver microsomes and eDNA-expressed CYP isoforms in vitro. The formation of lansoprazole sulfone from both enantiomers appeared to be catalyzed by single and low affinity enzyme. Lansoprazole 5-hydroxylation, however, appeared to be mediated by two kinetically distinct CYP enzymes.(omitted)

• BMB Reports
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• v.49 no.11
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• pp.590-597
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• 2016

Parasitic diseases remain an unarguable public health problem worldwide. Liver fluke Clonorchis sinensis is a high risk pathogenic parasitic helminth which is endemic predominantly in Asian countries, including Korea, China, Taiwan, Vietnam, and the far eastern parts of Russia, and is still actively transmitted. According to the earlier $8^{th}$ National Survey on the Prevalence of Intestinal Parasitic Infections in 2012, C. sinensis was revealed as the parasite with highest prevalence of 1.86% in general population among all parasite species surveyed in Korea. This fluke is now classified under one of the definite Group 1 human biological agents (carcinogens) by International Agency of Research on Cancer (IARC) along with two other parasites, Opisthorchis viverrini and Schistosoma haematobium. C. sinensis infestation is mainly linked to liver and biliary disorders, especially cholangiocarcinoma (CCA). For the purposes of this mini-review, we will only focus on C. sinensis and review pathogenesis and carcinogenesis of clonorchiasis, disease condition by C. sinensis infestation, and association between C. sinensis infestation and CCA. In this presentation, we briefly consider the current scientific status for progression of CCA by heavy C. sinensis infestation from the food-borne trematode and development of CCA.