• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.57-57
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• 2003

Epidemiological studies of arsenic have shown that chronic exposure to arsenic can result in an increased incidence of cancer of the lung, skin, bladder and liver. It is impossible that the toxicity study of arsenic in the human, we become to measure in vitro cytotoxicity of inorganic and organic arsenic in the human normal liver cells including Chang Liver and WRL. (omitted)

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.56-56
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• 2003

The reactivity and toxicity of arsenic compounds depend on the their oxidative states. Exposure to arsenic causes many human health effects, including cardiovascular, hepatic and renal disease, in addition to cancer in kidney, liver, lung, urinary bladder and skin. The cytotoxic effects of arsenite on normal hepatocyte, which most of its biotranfomation takes place. (omitted)

• YAKHAK HOEJI
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• v.52 no.2
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• pp.93-100
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• 2008

A liquid chromatographic method with tandom spectrometric detection (LC/MS/MS) for the simultaneous determination of doxifluridine and its active metabolite, 5-fluorouracil (5-FU) was developed over the concentration range of $5{\sim}2000$ ng/ml, respectively. Doxifluridine, 5-FU and internal standard, 5-chlorouracil (5-CU), were extracted from liver and intestine tissue via protein precipitation. Acetonitrile was used as the extraction solvent and the supernatant was evaporated and reconstructed in mobile phase. Optimum chromatographic separation was achieved on a Agilent Zorbax $C_{18}$ ($100\;mm{\times}2.1\;mm$, $3.5\;{\mu}m$) column with mobile phase run in isocratic with methanol : water (20 : 80, v/v). The flow rate was 0.2 ml/min with total cycle time of 5 min. The lower limit of quantification was validated at 5.0 ng/ml of liver and intestine tissue, for both doxifluridine and 5-FU, respectively. The intra-day and inter-day precision and accuracy of quality control (QC) samples were <11% coefficient of variation and <7% relative error from theoretical concentration for both analytes. In addition, the special designed stability study was performed, because the metabolism of doxifluridine occurs spontaneously even in ice bath for monkey liver. The stability of doxifluridine in liver and intestine of monkey and beagle dog was compared. It was found that bioanalytical validation could not be performed for the monkey liver; however, beagle dog's liver has relatively low speed of metabolism compared to monkey liver and instead of monkey liver, beagle dog's liver could be used for the validation. Bioanalytical validation could be performed in monkey intestine. Eventually, this developed method for liver and intestine will be useful in support of the toxicokinetic and pharmacokinetic studies of doxifluridine and 5-FU.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.385-393
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• 2021

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in N-acetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase-3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.

• Molecular & Cellular Toxicology
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• v.1 no.4
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• pp.275-280
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• 2005

Carbon tetrachloride ($CCl_4$) is well known hepatotoxicant. Its overdose cause severe centrilobular hepatic necrosis in human and experimental animals. We administered $CCl_{4}$ at low (0.2 mL/kg p.o.) and high (2 mL/kg p.o.) doses to mice. Mice were sacrificed at 24 h after administration. We evaluated liver toxicity by serum AST and ALT level and by microscopic observation. Using cDNA chip, we conducted gene expression analysis in liver. Mean serum activities of the hepatocellular leakage enzymes, ALT and AST, were significantly increased compare to control, respectively, in the low and high dose groups. H&E evaluation of stained liver sections revealed $CCl_{4}-related$ histopathological findings in mice. Moderate centrilobular hepatocellular necrosis was present in all $CCl_{4}$ treated mice. We found that gene expression pattern was very similar between low and high dose group. However, some stress related genes were differently expressed. These results could be a molecular signature for the degree of liver injury. Our data suggest that the degree of severity could be figure out by gene expression profiling.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2002.11a
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• pp.149-149
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• 2002

Epidemiologically the incidence of liver cancer is markedly sex-differentiated, with a much higher frequency in men than in women. In experimental animals, it is also higher in male than in female irrespective of carcinogen-induced or spontaneous tumors. Therefore, we tried to investigate the modulating effects of sex hormones in experimental hepatocarcinogenesis. For induction of liver tumors, mini-osmotic pump containing diethylnitrosamine at a dose level of 47.5mg was implanted into the peritoneal cavity of the rat at 6 weeks old. To remove the effects of male sex hormones, the animals of group 2 were castrated one week prior to DEN treatment. To see the effects of estrogen, pellet containing 1g or 10g of estradiol-3-benzoate was infused subcutaneously to the animals of group 3 and 4 one week prior to DEN treatment. The pellets were exchanged every 4 weeks until sacrifice. All animals were sacrificed at 26 weeks after DEN treatment. The tumor incidences in group 1 (DEN alone), group 2 (DEN +castration), group 3(DEN +EB 1g) and group 4 (DEN +EB 10g) were 100％ (15/15), 93.3％ (14/15), 85.7％ (12/14) and 66.7％ (10/15), respectively, showing that the value of group 4 is significantly different from that of group 1. Tumor multiplicity data of group 1, 2, 3 and 4 were 5.470.73, 2.800.51, 2.070.41 and 1.670.46, respectively, showing castration or EB treatment reduced number of liver tumors significantly (P<0.001). With immunohistochemistry and Western blotting of ER the expressions were detected in normal adjacent liver cells but decreased or lost in tumor cells. From these results we conclude that female sex hormone, especially estrogen, may act as a liver tumor suppressor, and it seemed that the down regulation of ER may be associated with liver tumor development.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.11a
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• pp.138-138
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• 2004

• Journal of Ginseng Research
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• v.35 no.1
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• pp.69-79
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• 2011

Hepatocellular carcinoma (HCC) is the fi fth most common malignancy in the world and complicates liver cirrhosis related to hepatitis C virus (HCV) in many cases. We evaluated the therapeutic effect of Korean red ginseng extract (KGE) in patients with chronic liver diseases. Thirty male and female patients with HCC and another thirty with liver cirrhosis were included. Each category was divided into two groups; the first was used as control group, and received medical therapy only and the second group received the medical therapy supplemented with KGE capsules. The treated group with HCC received three KGE capsules/day (900 mg) while the treated group with HCV received two KGE capsules/day (600 mg) for 11 weeks along with their medical therapy. All patients were subjected to clinical examination and laboratory investigations, including liver function tests (at baseline, after 6 weeks of treatment and at the end of the study) and abdominal ultrasonography. Patients showing focal hepatic lesions were subjected to triphasic spiral abdominal computerized tomography and alpha-fetoprotein (AFP). HCV RNA was determined quantitatively by Roche for patients in the HCV group. Results showed that the medical therapy alone failed to normalize the liver enzymes or decrease the virus concentration. KGE administration induced a significant improvement in liver function tests, decreased the tumor marker (AFP) levels, and decreased the viral titers in HCV patients. Thus, KGE demonstrated powerful therapeutic effects against HCV and liver cancer.

• Biomolecules & Therapeutics
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• v.17 no.2
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• pp.188-198
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• 2009

This work was conducted to investigate the effect of bisphenol A (BPA) on estradiol (E2) 2-and 4-hydroxylase activities in the liver, kidney and lung tissues of male and female rats. After intraperitoneal administration of BPA to male and female rats for 4 days at 0, 10, and 50 mg/kg, the conversion of the substrate for hepatic and extra-hepatic enzyme activities was measured by GC/MSD. The result showed decreases of body and organ weights at 50 mg/kg BPA of male and female rats. Male hepatic E2 2-hydroxylase activity was inhibited by 68% at 10 mg/kg and by 82% at 50 mg/kg BPA. Female hepatic E2 2-hydroxylase activity was decreased by 46% at 10 mg/kg and by 56% at 50 mg/kg to the control. E2 4-hydroxylase was inhibited by 57 and 57% at 10 mg/kg and 54 and 78% at 50 mg/kg in liver of female and male, respectively. The urinary excretion rate of 2-hydroxyestradiol (2-OHE), androsterone and testosterone in urine of female rats with 50 mg/kg BPA were decreased significantly. The results showed that 50 mg/kg BPA was decreased E2 2-and 4-hydroxylase activities in liver, but not in other tissues. The urinary excretion rates of 2-OHE, androsterone and testosterone were also decreased. In liver, estrogenic enzyme activity were higher in male than female. These results suggest that BPA can disrupt estrogen metabolism by suppressing E2 2-and 4-hydroxylase activities in the liver of male and female rats.

• Toxicological Research
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• v.30 no.2
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• pp.65-70
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• 2014

Recent episodes of severe air pollution in eastern Asia have been reported in the scientific literature and news media. Therefore, there is growing concern about the systemic effects of air pollution on human health. Along with the other well-known harmful effects of air pollution, recently, several animal models have provided strong evidence that air pollutants can induce liver toxicity and act to accelerate liver inflammation and steatosis. This review briefly describes examples where exposure to air pollutants was involved in liver toxicity, focusing on how particulate matter (PM) or carbon black (CB) may be translocated from lung to liver and what liver diseases are closely associated with these air pollutants.