• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.50-57
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• 1993

This study characterized the effect of liver injury produced by hepatotoxicants on the biliary and urinary excretion of acetaminophen(AA) metabolites. Liver damage was produced in male S.-D. rats, 24 hr after dosing with carbon tetrachloride(4CCl_4,$ 0.75 mι/kg, ip) or thioacetamide(TA, 200 mg/kg, ip), or 16 hr after administration of cadmium chloride(4CdCl_2,$ 3.9 mg/kg, iv). Liver damage without renal injury was confirmed by measuring serum enzymes, creatinine and BUN levels as well as by histopathological examination. AA and its metabolites were measured for 3 hr by HPLC in rats injected iv with 1 mmo1/kg of AA. The excreted amounts of AA-glucuronide into bile were reduced to 60~70% of control rats by hepatotoxicants, but did not change urinary excretion of AA-glucuronide and AA-sulfate. Treatments with $CCl_4,\; CdCl_2$ and TA decreased the total (biliary plus urinary) excretion of thioethers of AA(30~50% of control), suggesting that these toxicants decrease cytochrome P-450-mediated toxification of AA. However, treatments of $CdCl_2$and TA markedly enhanced the excretion of AA-mercapturate into urine. Thus, 4CdCl_2$ and TA not only influence the formation of AA-glutathione, but may also alter the excretory routes (i.e. bile and urine) for the elimination of AA-metabolite.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.3
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• pp.457-462
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• 2010

The purpose of this study is to investigate the effect of water extract from Artemisiae Argi Folium Fermented with Lactobacillus pentosus (AFL) on viability of human hepatocyte HepG2 cells treated with hepatotoxicants such as EtOH, gallic acid, nicotine, acetaminophen, acetaldehyde, and lipopolysaccharide. AFL (0~400 ug/mL) was treated with EtOH, gallic acid, nicotine, acetaminophen, acetaldehyde, and lipopolysaccharide. And the viability of HepG2 cells was measured by MTT assay. AFL at the high concentration such as 400 ug/mL showed to increase significantly viabilities of HepG2 cells compared with hepatotoxicants (EtOH, gallic acid, nicotine, acetaminophen, and lipopolysaccharide) only (p<0.05). AFL could be supposed to have the hepatoprotective effect against hepatotoxicants such as gallic acid, EtOH, nicotine, acetaminophen, and lipopolysaccharide at the high concentration.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.2
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• pp.284-289
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• 2010

The purpose of this study is to investigate the effect of water extract from Artemisiae Argi Folium Fermented with Sacchromyces cerevisiae (AFS) on viability of human hepatocyte HepG2 cells treated with hepatotoxicants such as EtOH, gallic acid, nicotine, acetaminophen, acetaldehyde, and lipopolysaccharide. AFS (0~400 ug/mL) was treated with EtOH, gallic acid, nicotine, acetaminophen, acetaldehyde, and lipopolysaccharide. And the viability of HepG2 cells was measured by MTT assay. AFS showed to increase significantly viabilities of HepG2 cells compared with hepatotoxicants (EtOH, gallic acid, nicotine, acetaminophen, and lipopolysaccharide) only (p<0.05). AFS could be supposed to have the hepatoprotective effect against hepatotoxicants such as gallic acid, EtOH, nicotine, acetaminophen, and lipopolysaccharide.

• Journal of Food Hygiene and Safety
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• v.9 no.2
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• pp.75-80
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• 1994

The effects of ursodeoxycholic acid (UDCA) were studied on the hepatotoxicity induced by several hepatotoxicants such as carbonte trachloride, thioacetamide and 1-naphthylisothiocyanate in ICR male mice. UDCA (50 mg/kg, 100 mg/kg) decreased the elevated serum bilirubin in carbon tetrachloride intoxicated mice, the elevated serum AST, alkaline phosphatase in thioacetamide intoxicated mice, the elevated serum AST and bilirubin in 1-naphthylisothiocyanate intoxicated mice.

• Molecular & Cellular Toxicology
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• v.2 no.1
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• pp.21-28
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• 2006

Gadolinium chloride ($GdCl_{3}$) was known to block Kupffer cells and generally its toxicity study based on blocking these cells. Therefore, $GdCl_{3}$ frequently used to study toxic mechanisms of hepatotoxicants inducing injury through Kupffer cells. We also tried to investigate the effect of $GdCl_{3}\;on\;CCl_{4}$ toxicity, typical hepatotoxicants. Administration of $GdCl_{3}$ to mice significantly suppressed AST (asparatate amino transferase), ALT (alanine amino transferase) levels which were increased by $CCl_{4}$ treatment. However, $GdCl_{3}$ didn't inhibit the phagocytotic activity of Kupffer cells. Malondialdehyde (MDA) is a good indicator of the degree of lipid peroxidation. In this study, MDA increased by $GdCl_{3}$ administration not by $CCl_{4}$. To understand the toxicity of $GdCl_{3}$, we analyzed global gene expression profile of mice liver after acute $GdCl_{3}$ injection. Four hundred fifty two genes were differentially expressed with more than 2-fold in at least one time point among 3 hr, 6 hr, and 24 hr. Several genes involved in fibrogenesis regulation. Several types of pro-collagens (Col1a2, Col5a2, Col6a3, and Col13a1) and tissue inhibitor of metal-loproteinase1 (TIMP1) were up regulated during all the time points. Genes related to growth factors, chemokines, and oxidative stress, which were known to control fibrogenesis, were significantly changed. In addition, $GdCl_{3}$ induced abnormal regulation between lipid synthesis and degradation related genes. These data will provide the information about influence of $GdCl_{3}$ to hepatotoxicity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.21 no.4
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• pp.341-347
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• 1992

In search for new drugs and methods of pharmacotherapy of liver damage , the pollen extracts was administrated to the experimental animals and ivnestigated its biochemical effects in the serum and liver when aromatic hepatotoxicants-phenybutazone, aniline and benzo(a) pyrene-was administered. As the results are the pretretment of azalea pollen was prevented the leakage of asartate aminotransaminase (AST), alanine aminotransfease(ALT), alkaline phosphatase (ALP) activity and bilirubin level to serum and liver, except serum lactate dehydrogenase (LDH) activity.

• BMB Reports
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• v.39 no.5
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• pp.479-491
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• 2006

Heme oxygenase (HO), the rate limiting enzyme in the breakdown of heme into carbon monoxide (CO), iron and bilirubin, has recently received overwhelming research attention. To date three mammalian HO isozymes have been identified, and the only inducible form is HO-1 while HO-2 and HO-3 are constitutively expressed. Advances in unveiling signal transduction network indicate that a battery of redox-sensitive transcription factors, such as activator protein-1 (AP-1), nuclear factor-kappa B (NF-${\kappa}B$) and nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases including mitogen-activated protein kinases play an important regulatory role in HO-1 gene induction. The products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression contributes to protection against liver damage induced by several chemical compounds such as acetaminophen, carbon tetrachloride and heavy metals, suggesting HO-1 induction as an important cellular endeavor for hepatoprotection. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect against chemically-induced liver injury as well as hepatocarcinogenesis.

• Toxicological Research
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• v.13 no.4
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• pp.385-391
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• 1997

Inductive effects of cytochrome P450 2B1 by $\alpha$- and $\beta$-ionone were characterized in individual liver lobes of male Sprague Dawley rats. When rats were administered ionones orally at 100, 300, and 600 mg/kg for 24 hr, cytochrome P450 2B1 was induced dose-dependently in liver S-9 fractions as measured by P450 2B-specific monooxygenases and Western immunoblotting. The activity of P450 1A- and P450 2B-specific monooxygenases was differentially expressed in each lobe of normal liver. In addition, the monooxygenase activity was induced by $\alpha$- and $\beta$-ionone with different potency in each lobe of the liver. Our present results indicate that the different induction of P450s by $\alpha$- and $\beta$-ionone in each lobe may explain different susceptibilities of rat liver lobes to certain hepatotoxicants which require metabolic activation for their toxicity and that $\alpha$- and $\beta$-ionone may be useful model inducers of P450 2B1 in studying the toxic mechanism of certain toxicants which may require the metabolic activation by P450.

• Molecular & Cellular Toxicology
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• v.1 no.3
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• pp.164-171
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• 2005

Toxicological studies have an object of detecting adverse effects of a chemical on an organism based on observed toxicity marker (i.e., serum biochemical markers and chemical-specific gene expression) or phenotypic outcome. To date, most toxicogenomic studies concentrated on hepatic toxicity. cDNA microarray analysis enable discrimination of the responses in animals exposed to different classes of hepatotoxicants. In an effort to further characterize the mechanisms of 2, 3, 7, 8,-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin)-mediated toxicity, comprehensive temporal-responsive microarray analyses were performed on hepatic tissue from Sprague-Dawley rats treated with TCDD. Hepatic gene expression profiles were monitored using custom DNA chip containing 490 cDNA clones related with toxicology. Gene expression analysis identified 26 features which exhibited a significant change. In this study, we observed that the genes related with oxidative stress in rats exposed to Dioxin, such as CYPIIA3 and glutathione S-transferase, were up-regulated at 24hr after exposure. In this study, we carried out to discover novel evidence for previously unknown gene expression patterns related to mechanism of hepatic toxicity in rats exposed to dioxin, and to elucidate the effects of dioxin on the gene expression after exposure to dioxin.

• YAKHAK HOEJI
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• v.56 no.2
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• pp.99-107
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• 2012

The protective effect of AI-1367 (Alnus japonica extract) on liver injury was investigated. Primary rat hepatocyte intoxication was induced by tert-butyl hydroperoxide (tBH), carbon tetrachloride ($CCl_4$), or D-glactosamine (D-GalN). Liver injury was induced by $CCl_4$, D-GalN or MCD (methionine choline deficient)-diet in mouse. The cellular leakage of lactate dehyrogenase and cell viability followed by the treatment of hepatotoxicants were significantly improved by AI-1367 treatment at a concentration range of 5~50 ${\mu}g/ml$ for tBH, 5~50 ${\mu}g/ml$ for D-GalN, and 5~100 ${\mu}g/ml$ for $CCl_4$, respectively. Treatment with AI-1367 (20, 10, 5 mg/kg, p.o.) on liver injury induced by subcutaneous injection of $CCl_4$ or D-GalN reduced significantly the levels of aspartate transaminase and alanine transaminase in serum. Histological observations revealed that fatty acid changes, hepatocyte necrosis and inflammatory cell infiltration in $CCl_4$ (D-GalN)-induced liver injury was improved by administration of AI-1367. AI-1367 treatment (10, 5, 2.5 mg/kg, p.o.) also significantly recovered the body weight change and serum levels of aspartate transaminase, alanine transaminase and triglyceride in liver injury induced by MCD diet. From these results, AI-1367 shows protective effects against tBH, $CCl_4$, D-GalN, or MCD diet-induced hepatotoxicity in vitro or in vivo.