• YAKHAK HOEJI
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• v.43 no.6
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• pp.756-761
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• 1999

Lipid peroxidation mediated by hydroxyl radicals which are generated during myocardial ischermia has suggested as a possible mechanism of ischemic myocardial damage. Recently, it has been reported that anti-arrhythmic action of lidocaine, a local anesthetic, is attributed to its "membrane-stabilizing" properties through scavenging free radicals, thus, inhibiting lipid peroxidation. Aldehyde oxidase and xanthine oxidase which catalyze the oxidation of many purine, pyrimidine and pteridine derivatives are known as free radical generating systems. In this experiment, we studied the effect of lidocaine and procainamide on the hepatic aldehyde and xanthine oxidase activity and antioxidative activities. It was found that lidocaine and procainamide inhibited both NADPH-dependent and independent lipid peroxidation. Both of tested compounds were found to be ineffective in inhibiting xanthine oxidase. Lidocaine and procainamide, however, inhibited aldehyde oxidase activity in vitro as well as in vivo. Based on the above results, lidocaine and procainamide could be employed as a therapeutic agent for aldehyde oxidaserelated disease.d disease.

• Molecular & Cellular Toxicology
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• v.2 no.1
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• pp.48-53
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• 2006

[ ${\alpha}-Naphthylisothiocyanate$ ] (ANIT) induces intrahepatic cholestasis, involving damage to biliary epitheial cells. This study investigates hepatic gene expression and histopathological alterations in response to ANIT treatment in order to elucidate early time response of ANIT-induced hepatotoxicity. ANIT was treated with single dose (3, 6, and 60 mg/kg) in corn oil by oral gavage. Serum biochemical and histopathological observation were performed for evaluation of hepatotoxicity level. Affymetrix oligo DNA chips were used for gene expression profile by ANIT-induced hetpatoxicity. Hepatic enzyme levels (ALT, AST, and ALP) were increased in 24 hr high dose group. In microscopic observations, moderate hepatocellular necrosis, were confirmed 24 hr high dose groups. We found that gene expression patterns were dependent on time and dose. Our selected genes were related inflammation and immunomodulation. In this study, ANIT-induced hepatotoxicity was involved in acute phase responses and provides evidence for role of neutrophil could be mechanism associated with ANIT-mediated hepatotoxicity.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.191.1-191.1
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• 2003

The anti-oxidant activities of Acanthopanax senticosus stems were investigated. The n-BuOH fraction of A. senticosus stems exhibited a significant decrease in serum transaminase activities elevated by hepatic damage induced by CCl$_4$-intoxication in rats. The n-BuOH fraction inhibited the sGPT activities by 65.79%. The n-BuOH fraction showed the increase in the anti-oxidant enzymes such as hepatic cytoso1ic superoxide dismutase, catalase and glutathione peroxidase activities by 30.31, 19.82 and 155%, respectively, in CCl$_4$-intoxicated rats. These results suggest that the stems of A. senticosus possess not only the hepatoprotective, but also the anti-oxidant activities in rats.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.5-5
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• 2021

Alcoholic and nonalcoholic steaohepatitis is a leading form of chronic liver disease with few biomakers ad treatment options currently available. a progressive disease of NAFLD may lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Recently, we extracted HIMH0021, which is an active flavonoid component in the Acer tegmentosum extract, has been shown to protect against liver damage caused by hepatic dysfunction. Therefore, in this study, we aimed to investigate whether HIMH0021 could regulate steatohepatitis and liver fibrosis during alcoholic or nonalcoholic metabolic process. HIMH0021, which was isolated from the active methanol extract of A. tegmentosum, inhibited alcohol-induced steatosis and attenuated the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during hepatocellular alcohol metabolism, both of which promote lipogenesis as well as liver inflammation. Treatment with HIMH0021 conferred protection against lipogenesis and liver injury, inhibited the expression of cytochrome P4502E1, and increased serum adiponectin levels in the mice subjected to chronic-plus-binge feeding. Furthermore, in hepatocytes, HIMH0021 activated fatty acid oxidation by activating pAMPK, which comprises pACC and CPT1a. These findings suggested that HIMH0021 could be used to target a TNFα-related pathway for treating patients with alcoholic hepatitis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2491-2494
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• 2013

Background: To evaluate the relative effectiveness of different treatments of hepatocellular carcinoma (HCC) via the hepatic artery. Materials and Methods: The study sample group consisted of 418 patients who were randomly selected from 2008 to 2012 with a first diagnosis of HCC and treated with transcatheter arterial chemoembolization (TACE) or without (TAE) chemotherapy or transcatheter arterial infusion (TAI). We collected data including tumor size preoperative and one month thereafter to compare change in areas across the three groups, along with various laboratory indexes for comparison. Results: The overall average change of areas was $240.8{\pm}72.1mm^2$. In the three groups it was $265.0{\pm}58.0mm^2$ vs. $250.5{\pm}51.9mm^2$ vs. $123.7{\pm}26.2mm^2$. In groups TACE and TAE values were larger than in group TAI (p<0.01), but the difference between the two was not statistically significant (p= 0.191). Additionally, U/L change of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in groups TACE and TAE was greater than in the TAI cases ($24.0{\pm}13.5$ vs. $20.9{\pm}12.1$ vs. $5.47{\pm}8.20$ and $25.6{\pm}13.5$ vs.$23.2{\pm}12.28$ vs.$5.48{\pm}14.3$) on the preoperative day and two days thereafter (p<0.01). Between the two groups there was no significant cariation (p= 0.320 and p= 0.609). However, the AST and ALT recovered to normal levels one month later on therapy with liver protecting drugs. Conclusion: The groups TACE and TAE demonstrated more effective reduction of tumor size than group TAI. While lipiodol caused acute liver function damage, this proved reversible.

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.438-445
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• 2009

We investigated global gene expression from both mouse liver and mouse hepatic cell lines treated with acetaminophen (APAP) in order to compare in vivo and in vitro profiles and to assess the feasibility of the two systems. During our analyses of gene expression profiles, we picked up several down-regulated genes, such as the cytochrome P450 family 51 (Cyp51), sulfotransferase family cytosolic 1C member 2 (Sult1c2), 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (Hmgcs1), and several genes that were up-regulated by APAP, such as growth arrest and DNA-damage-inducible 45 alpha (Gadd45a), transformation related protein 53 inducible nuclear protein 1 (Trp53inp1) and zinc finger protein 688 (Zfp688). For validation of gene function, synthesized short interfering RNAs (siRNAs) for these genes were transfected in a mouse hepatic cell line, BNL CL.2, for investigation of cell viability and mRNA expression level. We found that siRNA transfection of these genes induced down-regulation of respective mRNA expression and decreased cell viability. siRNA transfection for Cyp51 and others induced morphological alterations, such as membrane thickening and nuclear condensation. Taken together, siRNA transfection of these six genes decreased cell viability and induced alteration in cellular morphology, along with effective inhibition of respective mRNA, suggesting that these genes could be associated with APAP-induced toxicity. Furthermore, these genes may be used in the investigation of hepatotoxicity, for better understanding of its mechanism.

• YAKHAK HOEJI
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• v.52 no.4
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• pp.316-321
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• 2008

The hepatoprotection by the methanol extract of Oenanthe javanica DC (water dropwort) (OJME) was investigated in Sprague Dawley rats with inducing liver damage by acetaminophen. After OJME administration for 1 week, the increase of hepatic lipid peroxide level by acetaminophen-induced hepatotoxicity was significantly reduced. In case of phase I microsomal enzyme systems including cytochrome P-450, aminopyrine N-demethylase and aniline hydroxylase, any significant differences between in control and in OJME-pretreated group was observed after acetaminophen treatment. However, the pretreatment of OJME maintained the hepatic glutathione level and the activity of liver cytosolic glutathione S-transferase, which was significantly decreased by the acetaminophen intoxication. Among the glutathione-generating system, glutathione reductase was more responsible for its biosynthesis rather than ${\gamma}-glutamylcystein$ synthetase. OJME itself showed the strong inhibition activity on DPPH radical generation. In conclusion, OJME administration maintains the liver glutathione pool and hepatic glutathione S-transferase activity, in addition with its high anti-oxidative capability, to show hepatoprotective effect from acetaminophen intoxication.

• Parasites, Hosts and Diseases
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• v.49 no.4
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• pp.431-436
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• 2011

The onset, severity, and ultimate outcome of malaria infection are influenced by parasite-expressed virulence factors as well as by individual host responses to these determinants. In both humans and mice, liver injury follows parasite entry, persisting to the erythrocytic stage in the case of infection with the fatal strain of Plasmodium falciparum. Hepatic nuclear factor (HNF)-$1{\alpha}$ is a master regulator of not only the liver damage and adaptive responses but also diverse metabolic functions. In this study, we analyzed the expression of host HNF-$1{\alpha}$ in relation to malaria infection and evaluated its interaction with the 5'-untranslated region of subtilisin-like protease 2 (subtilase, Sub2). Recombinant human HNF-$1{\alpha}$ expressed by a lentiviral vector (LV HNF-$1{\alpha}$) was introduced into mice. Interestingly, differences in the activity of the 5'-untranslated region of the Pf-Sub2 promoter were detected in 293T cells, and LV HNF-$1{\alpha}$ was observed to influence promoter activity, suggesting that host HNF-$1{\alpha}$ interacts with the Sub2 gene.

• The Journal of Korean Medicine
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• v.31 no.5
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• pp.90-102
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• 2010

Objectives: This study was investigated the protective effect of Spatholobi Caulis water extract against cadmium (CdCl2, Cd)-induced hepatic toxicity in rats. Methods: To induce acute hepatic toxicity, Cd (4 mg/kg body weight) was dissolved in normal saline and intravenously injected into rats. Then, the rats received either a vehicle or silymarin (100 mg/kg) or Spatholobi Caulis water extract (30, 50 mg/kg/day) for 3 days, and were exposed to a single injection of Cd 24 h after the last Spatholobi Caulis/vehicle treatment. Results: Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were significantly increased by Cd treatment. In contrast, pretreatment with Spatholobi Caulis reduced ALT, AST and LDH. Cd-intoxicated liver damage was significantly inhibited by treatment of Spatholobi Caulis 30 and 50 mg/kg at histopathological observations in the present study. Conclusions: These results can be considered as direct evidence that Spatholobi Caulis has favorable inhibitory effects on the Cd-intoxicated liver damages. The efficacy of Spatholobi Caulis 30 mg/kg shows similar effects to that of silymarin 100 mg/kg, and more favorable hepatoprotective effects were observed in Spatholobi Caulis 50 mg/kg as compared with silymarin 100 mg/kg against Cd-intoxicated hepatopathies in the present study.

• Journal of the Korean Society of Food Science and Nutrition
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• v.28 no.4
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• pp.901-906
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• 1999

This study was designed to investigate the effect of Pueraria radix extract on lipid peroxidation in ethanol administered rats. Male sprague dawley rats were given 25% ethanol(2.5g per Kg body weight; E), 10% pueraria radix extract(CP), 25% ethanol and 10% pueraria radix extract(EP). The activity of hepatic superoxide dismutase was increased by ethanol and was lower in the EP group than in the E group. Hepatic catalase activity was increased by ethanol, but decreased by Pueraria radix extract. E group rats had significantly higher liver glutathione peroxidase activity. Activity of hepatic glutathione S transferase was higher in the CP group than in the other groups. No significant dif ferences was found in liver glutathione and lipid peroxide contents between control and EP group. These data indicate that the peroxidative damage associated with chronic ethanol consumption might be decreased by Pueraria radix extract.