• Journal of Integrative Natural Science
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• v.8 no.4
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• pp.258-266
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• 2015

Xanthine Oxidase is an enzyme, which oxidizes hypoxanthine to xanthine, and xanthine to uric acid. It is widely distributed throughout various organs including the liver, gut, lung, kidney, heart, brain and plasma. It is involved in gout pathogenesis. In this study, we have performed Comparative Molecular Field Analysis (CoMFA) on a series of 2-(indol-5-yl) thiazole derivatives as xanthine oxidase (XO) inhibitors to identify the structural variations with their inhibitory activities. Ligand based CoMFA models were generated based on atom-by-atom matching alignment. In atom-by-atom matching, the bioactive conformation of highly active molecule 11 was generated using systematic search. Compounds were aligned using the bioactive conformation and it is used for model generation. Different CoMFA models were generated using different alignments and the best model yielded a cross-validated $q^2$ of 0.698 with five components and non-cross-validated correlation coefficient ($r^2$) of 0.992 with Fisher value as 236.431, and an estimated standard error of 0.068. The predictive ability of the best CoMFA models was found to be $r^2_{pred}$0.653. The CoMFA study revealed that the $R_3$ position of the structure is important in influencing the biological activity of the inhibitors. Electro positive groups and bulkier substituents in this position enhance the biological activity.

• BMB Reports
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• v.30 no.4
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• pp.237-239
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• 1997

The effects of trichloroethylene (TRI) on the induction of cytochrome P-450 (CYP) and several other related enzymes in Sprague Dawley rats were investigated Rats were treated with TRI 150. 300. 600 mg/kg body weight in corn oil intra peritoneally once a day for 2 days. The total contents of microsomal CYP and cytochrome $b_5\;(b_5)$ decreased with the increase of TRI concentration. but the activity of p-nitrophenol hydroxylase increased with the increase of TRI dosage (p<0.05). Western blot analysis which utilized monoclonal antibodies against CYP2E1 also showed a significant increase in the CYP2E band density. The increase of the activity of pentoxyresolufin-O-deethylase also was observed with the TRI treatment (p<0.05) although there was no significant increase in the cytochrome CYP2B1/2 in Western blotting The TRI did not affect the induction of aryl hydrocarbon hydroxylase. These findings suggest that the CYP2E1 is the primary enzyme which could be induced by TRI treatment in rats.

• Food Science and Biotechnology
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• v.15 no.2
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• pp.238-243
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• 2006

The methanol extract of waxy brown rice fermented with Agrocybe cylindracea was prepared. The extract was then freeze dried and fed to rats at the level of 0.5, 1.0, 2.0 g/kg body weight for 14 days, followed by the treatment with carbon tetrachloride for three consecutive days to induce hepatotoxicity. After sacrificing the rats, the enzyme activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and ${\gamma}$-glutamyl transpeptidase (${\gamma}$-GTP) in serum was determined. Biochemical analysis on serum for albumin, total protein, triglyceride, and total as well as HDL-cholesterol were carried out along with a histopathological study of liver tissues. Based on these data, we suggest that the waxy brown rice cultured with A. cylindracea may exert hepatoprotective activity against hepatotoxicity caused by chemicals such as carbon tetrachloride.

• YAKHAK HOEJI
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• v.37 no.3
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• pp.270-277
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• 1993

It is well known that lipidperoxide, formed in vivo, induced the denaturation of enzyme and destruction of cell membrane to acute injury of tissue. Aralia elata have physiological activates, the improvement of lipid metabolism, antidiabetic activity etc., which was thought to have the relationship to lipid peroxidation. The anti-lipidperoxidative effect of Aralia elata have not yet established. In this study, we examined the anti-lipidperoxidative effects of Aralia elata (Butanol fraction) on CCI$_{4}$ induced lipidperoxidation in rats, and elucidated the anti-lipidperoxidative mechanism. In rat liver homogenate intoxicated with CCI$_{4}$ (0.5 ml/100g), BuOH fraction of Aralia elata (80 mg/Kg/day) exhibited 85.41% anti-lipidperoxidative effect but in serum 69.63% inhibitory effects, respectively. In mitochondrial and microsomal fraction showed inhibition of 55.85% and 69.30%, respectively. In order to elucidate the mechanism of anti-lipidperoxidation effects of Aralia elata, enzymatic (NADPH dependent) and non-enzymatic (Ascorbic acid catalyzed) reaction, in vitro, were performed. In enzymatic reation, Aralia elata exhibited 59.43% anti-lipidperoxidation effects, but in non-enzymatic reaction exhibited 43.27% inhibition. Therefore, it is noteworthy that antioxidative power of them may mainly results from the inhibition by enzymatic reaction.

• Korean Journal of Pharmacognosy
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• v.28 no.2
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• pp.88-92
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• 1997

The full NMR assignment of hispidulin 7-0-neohesperidoside (1) isolated from Cirsium japonicum var. ussuriense was made with the aid of 2D correlation NMR techniques such as HMQC and HMBC. To investigate detoxification of bromobenzene-induced hepatic lipid peroxidation by compound 1, hepatic lipid peroxide level and the activities of enzymes responsible for production and removal of epoxide were studied. The level of lipid peroxide elevated by bromobenzene was significantly reduced by compound 1. This compound administered daily over one week before intoxication with bromobenzene did not affect the activities of aminopyrine N-demethylase, aniline hydroxylase, glutathione S-transferase. Epoxide hydrolase activity was decreased significantly by bromobenzene, which was restored to the control level by pretreatment of persicarin. The results suggest that the bromobenzene-induced hepatic lipid peroxidation by compound 1 is reduced by enhancing the activity of epoxide hydrolase, an enzyme removing bromobenzene epoxide.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.67-67
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• 1995

Acyl-CoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) plays an important role in the control of intracellular free cholesterol content via its cholesterol esterifying activity. ACAT inhibitors are expected to be effective for treatment of atherosclerosis and hypercholesterolemia. In the course of a screening program for ACAT inhibitors from microbial sources, GERI-BP001 M, A, and B were isolated from the fermentation broth of a fungal strain. GERI-BP001 compounds were isolated from a culture broth of Aspergillus fumigatus F37 by acetone extraction, EtOAc extraction, SiO$_2$ column chromatography, and reverse phase HPLC. The structure of GERI-BP001 coumpounds were determined by $^1$H-NMR, $\^$l3/C-NMR, 2D-NMR, NOESY, and long range C-H COSY experiments. GERI-BP001 M, A, and B inhibit ACAT activity in an enzyme assay system using rat liver microsomes by 50% at concentrations of 75, 147, and 71 ${\mu}$M, respectively.

• Journal of Environmental Health Sciences
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• v.22 no.4
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• pp.91-101
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• 1996

Exposure indices are important tools which enable scientists to reliably predict and detect exposures to xenobiotics and resultant cell injury. Since the de novo synthesis of stress proteins can be detected early after exposure to some agents, analysis of toxicant-induced changes in gene expression, i.e. alterations in patterns of protein synthesis, may be useful to develop as biomarkers of exposure and toxicity. The acute and chronic effects of cadmium(Cd, $CdCl_2$ 20 mg/kg) on Wistar male rats were evaluated concerning cadmium contents, tissues enzyme activity, HSP expression. The results of the study were as follows: 1. Less cadmium was absorbed through the digestive tracts, but the ratio of contents in renal to hepatic cadmium was higher at 8 weeks after treatment. 2. ALT(alanine aminotransferase), AST(aspartate aminotransferase), glucose, BUN(blood urea nitrogen), creatinine, the key indices of the clinical changes in hepatic and renal function were significantly changed by the cadmium treatment after 1 week in liver, after 4 weeks in kidney. 3. Enhanced synthesis of 70 KDa relative molecular mass proteins were detected in 2 hours after cadmium exposure, with maximum activity occurring at 8~48 hours. Induction of $HSP_{70}$ was evident at proximal tubules and glomeruli in kidney. Testicular cells produced enough HSP to be detected normally. From the above results, it could be concluded that $HSP_{70}$ induction by the cadmium treatment was a rapid reaction to indicate the exposure of xenobiotics.

• Fisheries and Aquatic Sciences
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• v.22 no.1
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• pp.2.1-2.9
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• 2019

In the present study, the protective effects of Hizikia fusiforme and Chlorella sp. extracts on lead acetate-induced hepatotoxicity were investigated. Hepatic damage was induced in rats by intraperitoneal (i.p.) injection of lead acetate and the protective effects of H. fusiforme (HZK) and Chlorella sp. (CHL) extracts on lead acetate-induced hepatic damage in rat liver were examined. The results revealed significantly increased glutamic oxaloacetate and glutamic pyruvic transaminase levels in the group treated with lead acetate only (Pb group); oral administration of HZK and CHL extracts tended to decrease the enzyme levels similar to those observed in the control group. Regarding antioxidant enzymes, superoxide dismutase activity was increased in the Pb group and decreased in a concentration-dependent manner in the HZK- and CHL-treated groups. Glutathione levels were increased in a concentration-dependent manner in the HZK- and CHL-treated groups. There was no significant difference in catalase activity. Western blot analysis showed inflammation-related protein expression in mitogen-activated protein kinase and Nrf2 pathways was affected in the HZK- and CHL-treated groups. Therefore, HZK and CHL extracts exerted antioxidant and anti-inflammatory effects against lead acetate-induced hepatotoxicity. Development of functional health foods containing HZK and CHL extracts, which have hepatoprotective effects against inhaled lead acetate, should be considered.

• Biomedical Science Letters
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• v.14 no.1
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• pp.13-18
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• 2008

Excessive alcohol consumption is associated with increased risks of many diseases including cancer. Individuals who regularly consume excessive quantities of alcohol have a greater risk of developing head and neck cancers such as esophageal, pharyngeal and oral cavity cancers if they are deficient in ALDH2 expression compared to normal populations. We evaluated lipid peroxidation in Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. Malondialdehyde(MDA) level in liver tissue was evaluated as a biomarker of oxidative lipid peroxidation. Although the ethanol treatment did not increase the hepatic MDA level both in Aldh2 +/+ mice and in Aldh2 -/- mice, the MDA level was significant higher in the Aldh2 -/- mice than in the Aldh2 +/+ group. The MDA level was also significantly correlated with olive tail moment in blood and the level of 8-OHdG in liver tissue. This is a strong evidence to support our hypothesis that oxidative stress is more intense in Aldh2 -/- mice than in Aldh2 +/+ mice. Our results suggest that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated liver disease, including cancer.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.17 no.4
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• pp.239-247
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• 2014

Purpose: There are no studies of hepatic glycogen storage diseases (GSDs) other than type I and III in Korea. We aimed on investigating the characteristics of hepatic GSDs in Korea diagnosed and followed at a single center. Methods: We retrospectively analyzed patients who were diagnosed as GSD and followed at Samsung Medical Center from January, 1997 to December, 2013. Clinical manifestations, laboratory results, treatment, and prognosis were investigated. Results: Twenty-one patients were included in the study. The types of 17 patients were confirmed by enzyme activity tests and/or gene analysis. GSD Ia was diagnosed in 7 patients (33.3%), Ib in 1 patient (4.8%), III in 2 patients (9.5%), IV in 1 patient (4.8%), and IX in 6 patients (28.6%). Types other than GSD I constituted 52.9% (9/17) of the patients diagnosed with a specific type of hepatic GSD. The median age at presentation was 2 years. Hepatomegaly was observed in 95.2%, elevated liver transaminases in 90.5%, and hyperlactacidemia in 81.0% of the patients. The duration for follow-up was $77{\pm}62.0$ months. Uncooked corn starch was initiated in all the patients. No mortality was observed during the follow-up period, and liver transplantation was performed in 14.3%. Conclusion: Types other than GSD I comprised more than half of the patients diagnosed with a specific type of hepatic GSD. Clinical suspicion and thorough evaluation of hepatic GSDs in Korea should be focused not only on GSD I, but also on other types.