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Metabonomic analysis on urine metabolites related to hepatotoxicity in the rat treated with acetaminophen
Abstracts / Toxicology Letters 172S (2007) S1–S240
C40 Nickel release from metal textile accessories Michaela Zeiner 1 , Iva Rezic 2 , Ilse Steffan 1 1 University
of Vienna, Faculty of Chemistry, Vienna, Austria; 2 Faculty of Textile Technology, University of Zagreb, Zagreb, Croatia Metals like nickel, gold, or mercury are known as causes of allergic contact dermatitis. Elemental nickel and it is salts soluble in sweat can cause dermatitis during solubilization occurring after prolonged skin contact characterized by various skin symptoms (e.g. dryness, inflammation, eczema, blisters). The mechanism is yet not understood. The nickel ion itself is not antigenic. Different nickel complexes are bound to Langerhanscells which participate in immune regulation and are identified as being responsible for antigen processing and for presenting the antigen to T-lymphocyte-cells. Nickel-specific-T-lymphocytes are created that release lymphokines which stimulate the macrophages and natural killer cells resulting in allergic responses. Nickel sensitivity is reported for up to 15% of the female and 1% of the male population. In textile manufacturing metal parts are often used as indispensable accessories (e.g. buttons, zippers) and for decoration (e.g. grommets, rivets). The European Union’s Nickel Directive 94/27/EC (European Standard EN 1811:1998) prohibits the use of nickel in products used in prolonged contact with the human skin if the nickel release exceeds 0.5 g/cm2 per week. Products available in non EC-member-countries are not controlled by this Directive and thus may be of high risk for nickel sensitive people. Metal textile accessories were tested for their nickel release performing extraction experiments in artificial sweat and determining the nickel concentrations of the extracts. High nickel release was found which justifies further investigation. Reference European Standard EN 1811:1998E. Reference test method for release of nickel from products intended to come into direct and prolonged contact with the skin.
doi:10.1016/j.toxlet.2007.05.556
S221
P13 Other Z01 Metabonomic analysis on urine metabolites related to hepatotoxicity in the rat treated with acetaminophen Yosuke Ando, Shigehito Takeshita, Katsuyoshi Shibata, Kazunori Fujimoto, Sunao Manabe, Takashi Yamoto Daiichi Sankyo Co., Ltd., Fukuroi, Shizuoka, Japan Metabonomic analysis by liquid chromatography/timeof-flight mass spectrometry (LC/TOF MS) was conducted on rat urine in an acetaminophen-induced hepatotoxicity model and an l-buthionine (S, R)-sulfoximine (BSO)-induced hepatic glutathione depletion model to investigate biomarker candidates for the liver injury from the urine metabolites. MS spectra in the positive mode of LC/TOF MS were analyzed in the present study. At first, the endogenous metabolite peaks detected on the mass spectrum of the control urine samples without drug treatment were selected in order to eliminate the effect of metabolites derived from the treated drug. Out of these peaks, the candidate peaks related to the liver injury were extracted on the basis of the following statistical conditions: (1) acetaminophen-induced significant change (fold change to control average >|1.5|, P < 0.05); (2) correlation to the existing hepatotoxicity marker (Spearman’s rank correlation to log value of serum ALT activity); (3) correlation to hepatic glutathione depletion by treatment with BSO (Pearson’s r < −0.8). Principal components analysis on the extracted peaks enabled us to identify the two peaks that contributed to the significant clustering of the drug treated groups, and which were common in the three statistical conditions. The results suggest that these endogenous metabolite peaks are unique candidates for biomarkers which can be used to evaluate hepatotoxicity and glutathione homeostasis in the urine. doi:10.1016/j.toxlet.2007.05.558 Z02 Determination of naturally occurring antioxidant and anti-inflammatory compounds in fresh fruits by high performance liquid chromatography Goksel Arli, Nafiz Oncu Can Anadolu University, Eskisehir, Turkey As one of the major groups of natural pigments, anthocyanins are responsible for many of the colours of fruits
C40 Nickel release from metal textile accessories Michaela Zeiner 1 , Iva Rezic 2 , Ilse Steffan 1 1 University
of Vienna, Faculty of Chemistry, Vienna, Austria; 2 Faculty of Textile Technology, University of Zagreb, Zagreb, Croatia Metals like nickel, gold, or mercury are known as causes of allergic contact dermatitis. Elemental nickel and it is salts soluble in sweat can cause dermatitis during solubilization occurring after prolonged skin contact characterized by various skin symptoms (e.g. dryness, inflammation, eczema, blisters). The mechanism is yet not understood. The nickel ion itself is not antigenic. Different nickel complexes are bound to Langerhanscells which participate in immune regulation and are identified as being responsible for antigen processing and for presenting the antigen to T-lymphocyte-cells. Nickel-specific-T-lymphocytes are created that release lymphokines which stimulate the macrophages and natural killer cells resulting in allergic responses. Nickel sensitivity is reported for up to 15% of the female and 1% of the male population. In textile manufacturing metal parts are often used as indispensable accessories (e.g. buttons, zippers) and for decoration (e.g. grommets, rivets). The European Union’s Nickel Directive 94/27/EC (European Standard EN 1811:1998) prohibits the use of nickel in products used in prolonged contact with the human skin if the nickel release exceeds 0.5 g/cm2 per week. Products available in non EC-member-countries are not controlled by this Directive and thus may be of high risk for nickel sensitive people. Metal textile accessories were tested for their nickel release performing extraction experiments in artificial sweat and determining the nickel concentrations of the extracts. High nickel release was found which justifies further investigation. Reference European Standard EN 1811:1998E. Reference test method for release of nickel from products intended to come into direct and prolonged contact with the skin.
doi:10.1016/j.toxlet.2007.05.556
S221
P13 Other Z01 Metabonomic analysis on urine metabolites related to hepatotoxicity in the rat treated with acetaminophen Yosuke Ando, Shigehito Takeshita, Katsuyoshi Shibata, Kazunori Fujimoto, Sunao Manabe, Takashi Yamoto Daiichi Sankyo Co., Ltd., Fukuroi, Shizuoka, Japan Metabonomic analysis by liquid chromatography/timeof-flight mass spectrometry (LC/TOF MS) was conducted on rat urine in an acetaminophen-induced hepatotoxicity model and an l-buthionine (S, R)-sulfoximine (BSO)-induced hepatic glutathione depletion model to investigate biomarker candidates for the liver injury from the urine metabolites. MS spectra in the positive mode of LC/TOF MS were analyzed in the present study. At first, the endogenous metabolite peaks detected on the mass spectrum of the control urine samples without drug treatment were selected in order to eliminate the effect of metabolites derived from the treated drug. Out of these peaks, the candidate peaks related to the liver injury were extracted on the basis of the following statistical conditions: (1) acetaminophen-induced significant change (fold change to control average >|1.5|, P < 0.05); (2) correlation to the existing hepatotoxicity marker (Spearman’s rank correlation to log value of serum ALT activity); (3) correlation to hepatic glutathione depletion by treatment with BSO (Pearson’s r < −0.8). Principal components analysis on the extracted peaks enabled us to identify the two peaks that contributed to the significant clustering of the drug treated groups, and which were common in the three statistical conditions. The results suggest that these endogenous metabolite peaks are unique candidates for biomarkers which can be used to evaluate hepatotoxicity and glutathione homeostasis in the urine. doi:10.1016/j.toxlet.2007.05.558 Z02 Determination of naturally occurring antioxidant and anti-inflammatory compounds in fresh fruits by high performance liquid chromatography Goksel Arli, Nafiz Oncu Can Anadolu University, Eskisehir, Turkey As one of the major groups of natural pigments, anthocyanins are responsible for many of the colours of fruits