caa a22 4500 445853468 CHVBK 20180317145420.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00204-011-0664-7 doi (NATIONALLICENCE)springer-10.1007/s00204-011-0664-7 The difference of glutathione antioxidant system in newly weaned and young mice liver and its involvement in isoline-induced hepatotoxicity [Elektronische Daten] [Qing-Ning Liang, Yu-Chen Sheng, Ping Jiang, Li-Li Ji, Yu-Ye Xia, Yang Min, Zheng-Tao Wang] Cellular glutathione antioxidant system plays important roles in counteracting hepatotoxins-induced oxidative stress injury. The present study was designed to observe the differences of this system in newly weaned and young mice liver and its involvement in the susceptibility to isoline-induced liver injury. Our results showed that liver reduced glutathione (GSH) amounts were higher in newly weaned mice than young mice. Glutamate-cysteine ligase (GCL) activity was higher in newly weaned mice due to the higher expression of catalytic subunit of GCL (GCLC) protein and mRNA. However, the activities of glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) were higher in young mice liver, which might be due to the higher expression of GR, GPx-1, and GST-Pi proteins. Next, the results of AST analysis and histopathological evaluation showed that newly weaned mice demonstrated more severe liver injury induced by isoline. Furthermore, liver GSH amounts and the activities of GR, GPx, and GST were all lower in newly weaned mice than young mice after treated with isoline. Depletion of cellular GSH by d,l-buthionine-(S, R)-sulfoximine (BSO) aggravated isoline-induced cytotoxicity, while N-acetyl-l cysteine (NAC) ameliorated such cytotoxicity. Furthermore, the inhibitors of GR, GPx, and GST all aggravated isoline-induced cytotoxicity. In conclusion, our results demonstrated the differences of glutathione antioxidant system between newly weaned and young mice liver. Meanwhile, our results also revealed age-dependent liver injury induced by isoline for the first time, which might be due to the different responses of glutathione antioxidant system to isoline between newly weaned and young mice. Springer-Verlag, 2011 Glutathione antioxidant system nationallicence Isoline nationallicence Age-dependent difference nationallicence Hepatotoxicity nationallicence Oxidative stress nationallicence GSH : Reduced glutathione nationallicence GSSG : Oxidized glutathione nationallicence GCL : Glutamate-cysteine ligase nationallicence GR : Glutathione reductase nationallicence GPx : Glutathione peroxidase nationallicence GST : Glutathione-S-transferase nationallicence NAC : N-acetyl-l cysteine nationallicence ROS : Reactive oxygen species nationallicence DILI : Drug-induced liver injury nationallicence LPS : Lipopolysaccharide nationallicence PAs : Pyrrolizidine alkaloids nationallicence DTNB : 5, 5′-Dithio-bis (2-nitrobenzoic acid) nationallicence BCNU : 1,3-Bis(2-chloroethyl)-1-nitrourea nationallicence BSO : d,l-buthionine-(S, R)-sulfoximine nationallicence MA : Mercaptosuccinic acid nationallicence EA : Ethacrynic acid nationallicence CDNB : 1-Chloro-2, 4-dinitrophenol nationallicence RT-PCR : Reverse transcription-polymerase chain reaction nationallicence MTT : 3-(4, 5-Dimethyl-thiazol-2-yl) 2, 5-diphenyltetra-zolium bromide nationallicence AST : Aspartate aminotransferase nationallicence Liang Qing-Ning The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, 201210, Shanghai, China aut Sheng Yu-Chen Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, 200437, Shanghai, China aut Jiang Ping The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, 201210, Shanghai, China aut Ji Li-Li The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, 201210, Shanghai, China aut Xia Yu-Ye Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, 200437, Shanghai, China aut Min Yang Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, 200437, Shanghai, China aut Wang Zheng-Tao The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, 201210, Shanghai, China aut Archives of Toxicology Springer-Verlag 85/10(2011-10-01), 1267-1279 0340-5761 85:10<1267 2011 85 204 https://doi.org/10.1007/s00204-011-0664-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0664-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Liang Qing-Ning The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, 201210, Shanghai, China aut NATIONALLICENCE 700 1- Sheng Yu-Chen Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, 200437, Shanghai, China aut NATIONALLICENCE 700 1- Jiang Ping The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, 201210, Shanghai, China aut NATIONALLICENCE 700 1- Ji Li-Li The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, 201210, Shanghai, China aut NATIONALLICENCE 700 1- Xia Yu-Ye Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, 200437, Shanghai, China aut NATIONALLICENCE 700 1- Min Yang Department of Pharmacology, Shanghai Institute of Pharmaceutical Industry, 200437, Shanghai, China aut NATIONALLICENCE 700 1- Wang Zheng-Tao The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, 201210, Shanghai, China aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/10(2011-10-01), 1267-1279 0340-5761 85:10<1267 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 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