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Network analysis for nephrotoxicity using integrated profiling of metabolomic approach
S218
Abstracts / Toxicology Letters 205S (2011) S180–S300
P2123 Network analysis for nephrotoxicity using integrated profiling of metabolomic approach J.Y. Bae 1,∗ , B.M. Lee 2 , E.Y. Han 1 , I.Y. Ahn 1 , S.K. Lim 1 , M.J. Kwon 1 , S. Kim 2 , H.S. Kim 3 1 Sungkyunkwan University, Division of Toxicology, College of Pharmacy, Changan-Ku, Gyeonggi-Do, Suwon, Republic of Korea, 2 Department of Chemistry, Division of Toxicology, College of Pharmacy, Changan-Ku, Gyeonggi-Do, Suwon, Republic of Korea, 3 College of Pharmacy, Jangjeon-dong, Geumjeung-gu, Busan, Republic of Korea
Purpose: The aim of this study is to evaluate potential biomarkers for diagnosing nephrotoxicity by profiling and integrating metabolomics analyses from published papers or various databases. Method: Profiling metabolomics data is primarily based on published papers, various databases, such as KEGG, HMDB, SMPDB, and some visualization programming tools. For establishing a template database, all metabolites are organized by metabolome classes, nephrotoxicants, sample types (urine, sera, and tissues), and species (human, in vivo, and in vitro). Analysis of metabolic pathways involved in nephrotoxicity was performed to find nephrotoxicant-induced metabolism and to interpret the general trends of excess or deficiency of metabolites in living organisms. And the relationships between metabolisms within the whole metabolic networking enable to assume a common rule for nephrotoxic manifestations. Results of the study: Network analysis showed that amino acids metabolism is the most major metabolism related to nephrotoxicity in all types of samples, urine, sera and kidney tissues, and the next major metabolism is purine metabolism. Glycolysis plays a central role in all nephrotoxicity-relevant metabolisms. Purine metabolism, pyrimidine metabolism, citrate cycle, pyruvate metabolism, glycerolipid metabolism, and glutathione metabolism are other metabolisms which are associated with nephrotoxicity, and these metabolisms are linked to each other systematically. Acknowledgement: This research was support by a grant (10182KFDA992-1203) from Korea Food & Drug Administration in 2010. doi:10.1016/j.toxlet.2011.05.747 Oxydative stress P2124 Ability of Lactobacillus casei and Lactobacillus reuteri to protect against oxidative stress in rats fed aflatoxins-contaminated diet M.A. Abdel-Wahhab ∗ , A.S. Hathout, S.R. Mohamed, A.A. El-Nekeety, N.S. Hassan, S.E. Aly Food Toxicology & Contaminants, National Research Center, Cairo, Egypt Propose: The aim of the current study was to evaluate the protective role of Lactobacillus casei (L1) and Lactobacillus reuteri (L2) against aflatoxin (AFs)-induced oxidative stress in rats. Methods: Sixty female Sprague–Dawley rats were divided into 6 groups including the control group and the groups treated with L1 or L2 alone at a dose of 10 mL (1 × 1011 )/kg b.w or plus AFs (3 mg/kg diet) for 4 weeks. At the end of the treatments, blood and tissues samples were collected for biochemical and histological studies. The results of the study: The results indicated that AFs alone induced a
significant decrease in food intake and body weight and a significant increase in transaminase, alkaline phosphatase cholesterol, triglycerides, total lipids, creatinine, uric acid and nitric oxide in serum and lipid peroxidation in liver and kidney accompanied with a significant decrease in total antioxidant capacity. Treatments with L1 or L2 succeeded to induce a significant improvement in all the biochemical parameters and histological picture of the liver. Moreover, L2 was more effective than L1 and both can be used safely in functional foods. doi:10.1016/j.toxlet.2011.05.748
P2125 Protective effects of antioxidants against the pyrethroid alpha-cypermethrin-induced oxidative damage in vitro A. Anadón ∗ , A. Romero, E. Ramos, M.A. Martínez, V. Castellano, I. ˜ Ares, M. Martínez, M.R. Martínez-Larranaga Department of Toxicology and Pharmacology, Universidad Complutense de Madrid, Madrid, Spain Alpha-cypermethrin, a synthetic insecticide Type II pyrethroid, has broad-spectrum use in agriculture, domestic and veterinary applications due to its high bio-efficacy and low mammalian toxicity. The objective of this study was to investigate if melatonin, trolox (vitamin E analog) and N-acetylcystein, could provide differential protection added before or after alpha-cypermethrin-induced oxidative damage in SH-SY5Y neuroblastoma and HepG2 hepatoma cell lines. To corroborate such protective effects, we used the cell viability, virtually the mitochondrial activity of living cells, was measured by quantitative colorimetric assay with 3-[4,5dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) and nitric oxide (NO) production by Griess reaction. Viability decreased to 66% in cells treated with 10 M alpha-cypermethrin for 24 h. The preincubation with melatonin (1 M), trolox (1 M), and N-acetylcystein (1 mM) appears to have a more profound protective effect against alpha-cypermethrin-induced injury in both cell lines. The results demonstrate that melatonin, trolox and Nacetylcystein pre and post-treatment have remarkable antioxidant effects on SH-SY5Y neuroblastoma and HepG2 hepatoma cell lines and effectively protect against alpha-cypermethrin-induced oxidative. Acknowledgement: This work was supported by projects Ref. BSCHGR58/08(UCM), Ref. No. S2009/AGR-1469 (CAM) and Consolider-Ingenio 2010 No. CSD2007-063 (MEC), Spain. doi:10.1016/j.toxlet.2011.05.749
P2126 The effects of CoQ10 on the erythrocyte and liver tissue cholinesterase, NO and MDA levels in the acute organophosphate toxicity A. Bayir 1,∗ , H. Kara 2 , O. Koylu 3 , R. Kocabas¸ 4 , A. Ak 5 1
Emergency Department, Selcuklu, Selcuk University, Selcuklu Faculty of Medicine, Konya, Turkey, 2 Konya Numune Hospital, Konya, Turkey, 3 Meram Training Hospital, Konya, Turkey, 4 Meram Faculty of Medicine, Selc¸uk University, Konya, Turkey, 5 Selc¸uk University, Selc¸uklu Faculty of Medicine, Konya, Turkey Purpose: The aim of this study was to examine the effects of CoQ10 on the liver tissue and erytrocyte malondialdehyde (MDA), nitric oxide (NO) and choline esterase (CE) levels in acute
Abstracts / Toxicology Letters 205S (2011) S180–S300
P2123 Network analysis for nephrotoxicity using integrated profiling of metabolomic approach J.Y. Bae 1,∗ , B.M. Lee 2 , E.Y. Han 1 , I.Y. Ahn 1 , S.K. Lim 1 , M.J. Kwon 1 , S. Kim 2 , H.S. Kim 3 1 Sungkyunkwan University, Division of Toxicology, College of Pharmacy, Changan-Ku, Gyeonggi-Do, Suwon, Republic of Korea, 2 Department of Chemistry, Division of Toxicology, College of Pharmacy, Changan-Ku, Gyeonggi-Do, Suwon, Republic of Korea, 3 College of Pharmacy, Jangjeon-dong, Geumjeung-gu, Busan, Republic of Korea
Purpose: The aim of this study is to evaluate potential biomarkers for diagnosing nephrotoxicity by profiling and integrating metabolomics analyses from published papers or various databases. Method: Profiling metabolomics data is primarily based on published papers, various databases, such as KEGG, HMDB, SMPDB, and some visualization programming tools. For establishing a template database, all metabolites are organized by metabolome classes, nephrotoxicants, sample types (urine, sera, and tissues), and species (human, in vivo, and in vitro). Analysis of metabolic pathways involved in nephrotoxicity was performed to find nephrotoxicant-induced metabolism and to interpret the general trends of excess or deficiency of metabolites in living organisms. And the relationships between metabolisms within the whole metabolic networking enable to assume a common rule for nephrotoxic manifestations. Results of the study: Network analysis showed that amino acids metabolism is the most major metabolism related to nephrotoxicity in all types of samples, urine, sera and kidney tissues, and the next major metabolism is purine metabolism. Glycolysis plays a central role in all nephrotoxicity-relevant metabolisms. Purine metabolism, pyrimidine metabolism, citrate cycle, pyruvate metabolism, glycerolipid metabolism, and glutathione metabolism are other metabolisms which are associated with nephrotoxicity, and these metabolisms are linked to each other systematically. Acknowledgement: This research was support by a grant (10182KFDA992-1203) from Korea Food & Drug Administration in 2010. doi:10.1016/j.toxlet.2011.05.747 Oxydative stress P2124 Ability of Lactobacillus casei and Lactobacillus reuteri to protect against oxidative stress in rats fed aflatoxins-contaminated diet M.A. Abdel-Wahhab ∗ , A.S. Hathout, S.R. Mohamed, A.A. El-Nekeety, N.S. Hassan, S.E. Aly Food Toxicology & Contaminants, National Research Center, Cairo, Egypt Propose: The aim of the current study was to evaluate the protective role of Lactobacillus casei (L1) and Lactobacillus reuteri (L2) against aflatoxin (AFs)-induced oxidative stress in rats. Methods: Sixty female Sprague–Dawley rats were divided into 6 groups including the control group and the groups treated with L1 or L2 alone at a dose of 10 mL (1 × 1011 )/kg b.w or plus AFs (3 mg/kg diet) for 4 weeks. At the end of the treatments, blood and tissues samples were collected for biochemical and histological studies. The results of the study: The results indicated that AFs alone induced a
significant decrease in food intake and body weight and a significant increase in transaminase, alkaline phosphatase cholesterol, triglycerides, total lipids, creatinine, uric acid and nitric oxide in serum and lipid peroxidation in liver and kidney accompanied with a significant decrease in total antioxidant capacity. Treatments with L1 or L2 succeeded to induce a significant improvement in all the biochemical parameters and histological picture of the liver. Moreover, L2 was more effective than L1 and both can be used safely in functional foods. doi:10.1016/j.toxlet.2011.05.748
P2125 Protective effects of antioxidants against the pyrethroid alpha-cypermethrin-induced oxidative damage in vitro A. Anadón ∗ , A. Romero, E. Ramos, M.A. Martínez, V. Castellano, I. ˜ Ares, M. Martínez, M.R. Martínez-Larranaga Department of Toxicology and Pharmacology, Universidad Complutense de Madrid, Madrid, Spain Alpha-cypermethrin, a synthetic insecticide Type II pyrethroid, has broad-spectrum use in agriculture, domestic and veterinary applications due to its high bio-efficacy and low mammalian toxicity. The objective of this study was to investigate if melatonin, trolox (vitamin E analog) and N-acetylcystein, could provide differential protection added before or after alpha-cypermethrin-induced oxidative damage in SH-SY5Y neuroblastoma and HepG2 hepatoma cell lines. To corroborate such protective effects, we used the cell viability, virtually the mitochondrial activity of living cells, was measured by quantitative colorimetric assay with 3-[4,5dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) and nitric oxide (NO) production by Griess reaction. Viability decreased to 66% in cells treated with 10 M alpha-cypermethrin for 24 h. The preincubation with melatonin (1 M), trolox (1 M), and N-acetylcystein (1 mM) appears to have a more profound protective effect against alpha-cypermethrin-induced injury in both cell lines. The results demonstrate that melatonin, trolox and Nacetylcystein pre and post-treatment have remarkable antioxidant effects on SH-SY5Y neuroblastoma and HepG2 hepatoma cell lines and effectively protect against alpha-cypermethrin-induced oxidative. Acknowledgement: This work was supported by projects Ref. BSCHGR58/08(UCM), Ref. No. S2009/AGR-1469 (CAM) and Consolider-Ingenio 2010 No. CSD2007-063 (MEC), Spain. doi:10.1016/j.toxlet.2011.05.749
P2126 The effects of CoQ10 on the erythrocyte and liver tissue cholinesterase, NO and MDA levels in the acute organophosphate toxicity A. Bayir 1,∗ , H. Kara 2 , O. Koylu 3 , R. Kocabas¸ 4 , A. Ak 5 1
Emergency Department, Selcuklu, Selcuk University, Selcuklu Faculty of Medicine, Konya, Turkey, 2 Konya Numune Hospital, Konya, Turkey, 3 Meram Training Hospital, Konya, Turkey, 4 Meram Faculty of Medicine, Selc¸uk University, Konya, Turkey, 5 Selc¸uk University, Selc¸uklu Faculty of Medicine, Konya, Turkey Purpose: The aim of this study was to examine the effects of CoQ10 on the liver tissue and erytrocyte malondialdehyde (MDA), nitric oxide (NO) and choline esterase (CE) levels in acute