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214 Abstracts / Toxicology L

Mulberry extract caused a significant rise in the above men-ioned analytes in both control and diabetic animals.

Based on these data, it is concluded that caution should be takenith the use of mulberry extract or drugs containing this herb iniabetic patients. In the case of chronic use of this herbal product,

iver and kidney function need to be monitored.

oi:10.1016/j.toxlet.2010.03.719

206-031crolein induces heme oxygenase 1 through PKC-� and P38athway in HepG2

.Y. Song, N.J. Lee, S.E. Lee, H.J. Ahn

Kyung Hee University, South Korea

crolein is an alpha, beta-unsaturated aldehyde present in cigarettemoke, and is also product of lipid peroxidation. Heme oxygenase-(HO-1) plays a critical role in preventing to oxidative stress and

ther cellular functions, and induces proliferation and viabilityf tumor cells. Acrorein is well-known to induce HO-1, althoughhe signal pathway has not been fully elucidated. In this study,e examine the signal pathway of HO-1 induction by acrolein inuman hapatocellular carcinoma (HepG2). The cell was treatedith acrolein to induce HO-1. HO-1 expression by acrolein sig-al pathway was measured by using Western blot, RT-PCR and

mmunofluorescence staining analyses. We demonstrated thatow concentrations of acrolein remarkably increased HO-1 mRNAnd protein level. Acrolein-mediated HO-1 induction was notablyecreased by PKC-� selective inhibitor rottlerin and p38 selective

nhibitor SB203580. No significant effect of block on HO-1 induc-ion by acrolein was observed with the pretreatment of wortmanina PI3K) and mitogen-activated protein kinase (MAPK) pathwaynhibitors, PD98059 (an ERK 1/2) and SP600125(a JNK). In conclu-ion, our results indicate that acrolein enhances the expression ofO-1 through PKC-� and p38 pathways.

oi:10.1016/j.toxlet.2010.03.720

206-032valuation of zebrafish as a model to predict humanepatotoxicity

. Callol, A. Letamendia, O. Holgado, M. Diez

Biobide, Spain

rug-induced hepatotoxicity is one of the most important causes ofrug withdrawal in the process of drug discovery. The low correla-ion of the in vitro cytotoxicity studies, with human hepatotoxicity,specially in the early stages of drug discovery, make human hepa-otoxicity difficult to predict. Therefore the finding of new methodsnd models to predict hepatotoxicity is a growing area of research.

The zebrafish model has been extensively studied in the lastecades for their ability to regenerate. Specifically, the liver is onef the organs with the highest regenerative capacity and researchver the past 10 years have characterized many of the mechanismshat occur during this process leading to an important knowledgef the signaling pathways that govern zebrafish liver function and

evelopment.

Therefore, because of the functional similarities as well as ofevelopment between the liver of zebrafish and mammals, weropose to analyze the potential of zebrafish for prediction of hep-totoxic agents. For this purpose, the following aspects have been

196S (2010) S37–S351

studied: (i) the stage at which adult liver markers are expressedhas been identified. (ii) Several techniques have been developedfor assessing the hepatotoxicity of a compound in zebrafish. (iii)These techniques have been validated by testing different drugs.(iv) The results were compared with those obtained in mammals.

Our results indicate that zebrafish embryos could be used as analternative model in the drug development process complementingthe information of in vitro models and mammals and providingpharmaceutical industry of new assays which might decrease thecurrent huge gap between in vitro and in vivo assays.

doi:10.1016/j.toxlet.2010.03.721

P206-033l-Serine ameliorate the acute ethanol induced steatosis inmice by inhibiting the maturation of sterol regulatory elementbinding protein-1c

H.Q. Yin, Y.T. Je, H.S. Choi, B.H. Lee

College of Pharmacy and Research Institute of PharmaceuticalSciences, Seoul National University, South Korea

Increasing evidence showed that sterol regulatory element bindingprotein-1c (SREBP-1c) play an important role in ethanol-inducedsteatosis. In this study we evaluated the effects of l-serine (l-ser)on the acute ethanol-induced steatosis and elucidated the possiblemechanisms of action in terms of the inhibition of the maturationof SREBP-1c. In vitro studies showed that treatment of H4IIEC3rat hepatoma cells with ethanol increased the lipid droplets inthe cells, whereas cotreatment with l-ser completely reversedthe fat accumulation. l-Ser treatment decreased the expressionof insulin-induced gene-1 (INSIG-1) and inhibited the maturationand translocation of SREBP-1c to the nucleus. Mammalian sirtuin1 (SIRT1), a NAD+-dependent class III protein deacetylase was notaffected by l-ser treatment. Male C57BL/6 mice received ethanol(5 g/kg body weight) by gavage every 12 h for a total 3 times. l-Ser (200 mg/kg body weight) was administrated by gavage for thelast two ethanol treatment. l-Ser treatment significantly decreasedthe ethanol-induced fatty liver changes and liver triglyceride con-tent. The Inhibition of the maturation of SREBP-1c protein wasalso observed in l-ser administrated mice. These results demon-strate that l-ser may be a promising candidate for development asa therapeutic agent for ethanol-induced steatosis.

doi:10.1016/j.toxlet.2010.03.722

P206-034Modulation of hepatic drug metabolism in influenza infectedmice. Preventive effect of polyphenols isolated from Geraniumsanguineum L.

E. Encheva 1, L. Tancheva 1, S. Abarova 1, J. Serkedjieva 2, S.Ivantcheva 3

1 Institute of Neurobiology, Bulgarian Academy of Sciences, Bulgaria,2 Institute of Microbiology at Bulgarian Academy of Sciences,Bulgaria, 3 Institute of Botany at Bulgarian Academy of Sciences,Bulgaria

As free-radical disease the influenza virus infection can be affectedeffectively by antioxidant treatment (Tantcheva et al., 2001,2002, 2003). Polyphenol extract from Geranium sanguineum L.demonstrated significant antioxidant and antiviral activity in vivo(Manolova, 1998). Using experimental model of influenza virus