Effects of C2-Ceramide and Oltipraz on Hepatocyte Nuclear Factor-1 and Glutathione S-Transferase A1 in Acetaminophen-Mediated Acute Mice Liver Injury
In this study, acetaminophen (APAP)-induced acute liver injury mice model was used to investigate the effects of C2-ceramide and oltipraz on hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase A1 (GSTA1). Notably, C2-ceramide caused alteration in mice serum transaminases and liver tiss...
Ausführliche Beschreibung
Autor*in: |
Xin Ma [verfasserIn] Yicong Chang [verfasserIn] Yuanyuan Zhang [verfasserIn] Ishfaq Muhammad [verfasserIn] Chenxi Shi [verfasserIn] Rui Li [verfasserIn] Changwen Li [verfasserIn] Zhi Li [verfasserIn] Yuexia Lin [verfasserIn] Qing Han [verfasserIn] Fangping Liu [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2018 |
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Übergeordnetes Werk: |
In: Frontiers in Pharmacology - Frontiers Media S.A., 2010, 9(2018) |
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Übergeordnetes Werk: |
volume:9 ; year:2018 |
Links: |
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DOI / URN: |
10.3389/fphar.2018.01009 |
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Katalog-ID: |
DOAJ05083715X |
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10.3389/fphar.2018.01009 doi (DE-627)DOAJ05083715X (DE-599)DOAJc5b1d11ccce7478e8f159e1cfe0e4ca3 DE-627 ger DE-627 rakwb eng RM1-950 Xin Ma verfasserin aut Effects of C2-Ceramide and Oltipraz on Hepatocyte Nuclear Factor-1 and Glutathione S-Transferase A1 in Acetaminophen-Mediated Acute Mice Liver Injury 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In this study, acetaminophen (APAP)-induced acute liver injury mice model was used to investigate the effects of C2-ceramide and oltipraz on hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase A1 (GSTA1). Notably, C2-ceramide caused alteration in mice serum transaminases and liver tissue indexes, and aggravated hepatic injury, while oltipraz alleviated hepatic injury. By screening, the optimal concentrations of C2-ceramide and oltipraz were confirmed to be 120 and 150 μmol/L, respectively. In histopathology, karyolysis and more necrotic cells and bleeding spots were appeared on administration of C2-ceramide, but only a small amount of inflammatory cells infiltration was seen after oltipraz treatment. In addition, RT-PCR and western blot results revealed that the mRNA and protein expression levels of HNF-1 and GSTA1 in liver were significantly decreased (p < 0.01) with the administration of 120 μmol/L C2-ceramide. Meanwhile, GSTA1 content in serum increased up to 1.27-fold. In contrast, 150 μmol/L oltipraz incorporation to APAP model mice resulted in obvious elevation (p < 0.01) in the mRNA and protein expression levels of HNF-1 and GSTA1 in liver, and serum GSTA1 content decreased up to 0.77-fold. In conclusion, C2-ceramide could down-regulate the expression of HNF-1 and GSTA1 which exacerbated hepatic injury, while oltipraz could up-regulate the expression of HNF-1 and GSTA1 which mitigated hepatic injury. GSTA1 HNF-1 C2-ceramide oltipraz acetaminophen liver injury Therapeutics. Pharmacology Xin Ma verfasserin aut Yicong Chang verfasserin aut Yuanyuan Zhang verfasserin aut Ishfaq Muhammad verfasserin aut Chenxi Shi verfasserin aut Rui Li verfasserin aut Rui Li verfasserin aut Changwen Li verfasserin aut Zhi Li verfasserin aut Yuexia Lin verfasserin aut Qing Han verfasserin aut Fangping Liu verfasserin aut Fangping Liu verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 9(2018) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:9 year:2018 https://doi.org/10.3389/fphar.2018.01009 kostenfrei https://doaj.org/article/c5b1d11ccce7478e8f159e1cfe0e4ca3 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2018.01009/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018 |
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10.3389/fphar.2018.01009 doi (DE-627)DOAJ05083715X (DE-599)DOAJc5b1d11ccce7478e8f159e1cfe0e4ca3 DE-627 ger DE-627 rakwb eng RM1-950 Xin Ma verfasserin aut Effects of C2-Ceramide and Oltipraz on Hepatocyte Nuclear Factor-1 and Glutathione S-Transferase A1 in Acetaminophen-Mediated Acute Mice Liver Injury 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In this study, acetaminophen (APAP)-induced acute liver injury mice model was used to investigate the effects of C2-ceramide and oltipraz on hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase A1 (GSTA1). Notably, C2-ceramide caused alteration in mice serum transaminases and liver tissue indexes, and aggravated hepatic injury, while oltipraz alleviated hepatic injury. By screening, the optimal concentrations of C2-ceramide and oltipraz were confirmed to be 120 and 150 μmol/L, respectively. In histopathology, karyolysis and more necrotic cells and bleeding spots were appeared on administration of C2-ceramide, but only a small amount of inflammatory cells infiltration was seen after oltipraz treatment. In addition, RT-PCR and western blot results revealed that the mRNA and protein expression levels of HNF-1 and GSTA1 in liver were significantly decreased (p < 0.01) with the administration of 120 μmol/L C2-ceramide. Meanwhile, GSTA1 content in serum increased up to 1.27-fold. In contrast, 150 μmol/L oltipraz incorporation to APAP model mice resulted in obvious elevation (p < 0.01) in the mRNA and protein expression levels of HNF-1 and GSTA1 in liver, and serum GSTA1 content decreased up to 0.77-fold. In conclusion, C2-ceramide could down-regulate the expression of HNF-1 and GSTA1 which exacerbated hepatic injury, while oltipraz could up-regulate the expression of HNF-1 and GSTA1 which mitigated hepatic injury. GSTA1 HNF-1 C2-ceramide oltipraz acetaminophen liver injury Therapeutics. Pharmacology Xin Ma verfasserin aut Yicong Chang verfasserin aut Yuanyuan Zhang verfasserin aut Ishfaq Muhammad verfasserin aut Chenxi Shi verfasserin aut Rui Li verfasserin aut Rui Li verfasserin aut Changwen Li verfasserin aut Zhi Li verfasserin aut Yuexia Lin verfasserin aut Qing Han verfasserin aut Fangping Liu verfasserin aut Fangping Liu verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 9(2018) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:9 year:2018 https://doi.org/10.3389/fphar.2018.01009 kostenfrei https://doaj.org/article/c5b1d11ccce7478e8f159e1cfe0e4ca3 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2018.01009/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018 |
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10.3389/fphar.2018.01009 doi (DE-627)DOAJ05083715X (DE-599)DOAJc5b1d11ccce7478e8f159e1cfe0e4ca3 DE-627 ger DE-627 rakwb eng RM1-950 Xin Ma verfasserin aut Effects of C2-Ceramide and Oltipraz on Hepatocyte Nuclear Factor-1 and Glutathione S-Transferase A1 in Acetaminophen-Mediated Acute Mice Liver Injury 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In this study, acetaminophen (APAP)-induced acute liver injury mice model was used to investigate the effects of C2-ceramide and oltipraz on hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase A1 (GSTA1). Notably, C2-ceramide caused alteration in mice serum transaminases and liver tissue indexes, and aggravated hepatic injury, while oltipraz alleviated hepatic injury. By screening, the optimal concentrations of C2-ceramide and oltipraz were confirmed to be 120 and 150 μmol/L, respectively. In histopathology, karyolysis and more necrotic cells and bleeding spots were appeared on administration of C2-ceramide, but only a small amount of inflammatory cells infiltration was seen after oltipraz treatment. In addition, RT-PCR and western blot results revealed that the mRNA and protein expression levels of HNF-1 and GSTA1 in liver were significantly decreased (p < 0.01) with the administration of 120 μmol/L C2-ceramide. Meanwhile, GSTA1 content in serum increased up to 1.27-fold. In contrast, 150 μmol/L oltipraz incorporation to APAP model mice resulted in obvious elevation (p < 0.01) in the mRNA and protein expression levels of HNF-1 and GSTA1 in liver, and serum GSTA1 content decreased up to 0.77-fold. In conclusion, C2-ceramide could down-regulate the expression of HNF-1 and GSTA1 which exacerbated hepatic injury, while oltipraz could up-regulate the expression of HNF-1 and GSTA1 which mitigated hepatic injury. GSTA1 HNF-1 C2-ceramide oltipraz acetaminophen liver injury Therapeutics. Pharmacology Xin Ma verfasserin aut Yicong Chang verfasserin aut Yuanyuan Zhang verfasserin aut Ishfaq Muhammad verfasserin aut Chenxi Shi verfasserin aut Rui Li verfasserin aut Rui Li verfasserin aut Changwen Li verfasserin aut Zhi Li verfasserin aut Yuexia Lin verfasserin aut Qing Han verfasserin aut Fangping Liu verfasserin aut Fangping Liu verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 9(2018) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:9 year:2018 https://doi.org/10.3389/fphar.2018.01009 kostenfrei https://doaj.org/article/c5b1d11ccce7478e8f159e1cfe0e4ca3 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2018.01009/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018 |
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10.3389/fphar.2018.01009 doi (DE-627)DOAJ05083715X (DE-599)DOAJc5b1d11ccce7478e8f159e1cfe0e4ca3 DE-627 ger DE-627 rakwb eng RM1-950 Xin Ma verfasserin aut Effects of C2-Ceramide and Oltipraz on Hepatocyte Nuclear Factor-1 and Glutathione S-Transferase A1 in Acetaminophen-Mediated Acute Mice Liver Injury 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In this study, acetaminophen (APAP)-induced acute liver injury mice model was used to investigate the effects of C2-ceramide and oltipraz on hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase A1 (GSTA1). Notably, C2-ceramide caused alteration in mice serum transaminases and liver tissue indexes, and aggravated hepatic injury, while oltipraz alleviated hepatic injury. By screening, the optimal concentrations of C2-ceramide and oltipraz were confirmed to be 120 and 150 μmol/L, respectively. In histopathology, karyolysis and more necrotic cells and bleeding spots were appeared on administration of C2-ceramide, but only a small amount of inflammatory cells infiltration was seen after oltipraz treatment. In addition, RT-PCR and western blot results revealed that the mRNA and protein expression levels of HNF-1 and GSTA1 in liver were significantly decreased (p < 0.01) with the administration of 120 μmol/L C2-ceramide. Meanwhile, GSTA1 content in serum increased up to 1.27-fold. In contrast, 150 μmol/L oltipraz incorporation to APAP model mice resulted in obvious elevation (p < 0.01) in the mRNA and protein expression levels of HNF-1 and GSTA1 in liver, and serum GSTA1 content decreased up to 0.77-fold. In conclusion, C2-ceramide could down-regulate the expression of HNF-1 and GSTA1 which exacerbated hepatic injury, while oltipraz could up-regulate the expression of HNF-1 and GSTA1 which mitigated hepatic injury. GSTA1 HNF-1 C2-ceramide oltipraz acetaminophen liver injury Therapeutics. Pharmacology Xin Ma verfasserin aut Yicong Chang verfasserin aut Yuanyuan Zhang verfasserin aut Ishfaq Muhammad verfasserin aut Chenxi Shi verfasserin aut Rui Li verfasserin aut Rui Li verfasserin aut Changwen Li verfasserin aut Zhi Li verfasserin aut Yuexia Lin verfasserin aut Qing Han verfasserin aut Fangping Liu verfasserin aut Fangping Liu verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 9(2018) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:9 year:2018 https://doi.org/10.3389/fphar.2018.01009 kostenfrei https://doaj.org/article/c5b1d11ccce7478e8f159e1cfe0e4ca3 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2018.01009/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018 |
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10.3389/fphar.2018.01009 doi (DE-627)DOAJ05083715X (DE-599)DOAJc5b1d11ccce7478e8f159e1cfe0e4ca3 DE-627 ger DE-627 rakwb eng RM1-950 Xin Ma verfasserin aut Effects of C2-Ceramide and Oltipraz on Hepatocyte Nuclear Factor-1 and Glutathione S-Transferase A1 in Acetaminophen-Mediated Acute Mice Liver Injury 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In this study, acetaminophen (APAP)-induced acute liver injury mice model was used to investigate the effects of C2-ceramide and oltipraz on hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase A1 (GSTA1). Notably, C2-ceramide caused alteration in mice serum transaminases and liver tissue indexes, and aggravated hepatic injury, while oltipraz alleviated hepatic injury. By screening, the optimal concentrations of C2-ceramide and oltipraz were confirmed to be 120 and 150 μmol/L, respectively. In histopathology, karyolysis and more necrotic cells and bleeding spots were appeared on administration of C2-ceramide, but only a small amount of inflammatory cells infiltration was seen after oltipraz treatment. In addition, RT-PCR and western blot results revealed that the mRNA and protein expression levels of HNF-1 and GSTA1 in liver were significantly decreased (p < 0.01) with the administration of 120 μmol/L C2-ceramide. Meanwhile, GSTA1 content in serum increased up to 1.27-fold. In contrast, 150 μmol/L oltipraz incorporation to APAP model mice resulted in obvious elevation (p < 0.01) in the mRNA and protein expression levels of HNF-1 and GSTA1 in liver, and serum GSTA1 content decreased up to 0.77-fold. In conclusion, C2-ceramide could down-regulate the expression of HNF-1 and GSTA1 which exacerbated hepatic injury, while oltipraz could up-regulate the expression of HNF-1 and GSTA1 which mitigated hepatic injury. GSTA1 HNF-1 C2-ceramide oltipraz acetaminophen liver injury Therapeutics. Pharmacology Xin Ma verfasserin aut Yicong Chang verfasserin aut Yuanyuan Zhang verfasserin aut Ishfaq Muhammad verfasserin aut Chenxi Shi verfasserin aut Rui Li verfasserin aut Rui Li verfasserin aut Changwen Li verfasserin aut Zhi Li verfasserin aut Yuexia Lin verfasserin aut Qing Han verfasserin aut Fangping Liu verfasserin aut Fangping Liu verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 9(2018) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:9 year:2018 https://doi.org/10.3389/fphar.2018.01009 kostenfrei https://doaj.org/article/c5b1d11ccce7478e8f159e1cfe0e4ca3 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2018.01009/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018 |
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effects of c2-ceramide and oltipraz on hepatocyte nuclear factor-1 and glutathione s-transferase a1 in acetaminophen-mediated acute mice liver injury |
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Effects of C2-Ceramide and Oltipraz on Hepatocyte Nuclear Factor-1 and Glutathione S-Transferase A1 in Acetaminophen-Mediated Acute Mice Liver Injury |
abstract |
In this study, acetaminophen (APAP)-induced acute liver injury mice model was used to investigate the effects of C2-ceramide and oltipraz on hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase A1 (GSTA1). Notably, C2-ceramide caused alteration in mice serum transaminases and liver tissue indexes, and aggravated hepatic injury, while oltipraz alleviated hepatic injury. By screening, the optimal concentrations of C2-ceramide and oltipraz were confirmed to be 120 and 150 μmol/L, respectively. In histopathology, karyolysis and more necrotic cells and bleeding spots were appeared on administration of C2-ceramide, but only a small amount of inflammatory cells infiltration was seen after oltipraz treatment. In addition, RT-PCR and western blot results revealed that the mRNA and protein expression levels of HNF-1 and GSTA1 in liver were significantly decreased (p < 0.01) with the administration of 120 μmol/L C2-ceramide. Meanwhile, GSTA1 content in serum increased up to 1.27-fold. In contrast, 150 μmol/L oltipraz incorporation to APAP model mice resulted in obvious elevation (p < 0.01) in the mRNA and protein expression levels of HNF-1 and GSTA1 in liver, and serum GSTA1 content decreased up to 0.77-fold. In conclusion, C2-ceramide could down-regulate the expression of HNF-1 and GSTA1 which exacerbated hepatic injury, while oltipraz could up-regulate the expression of HNF-1 and GSTA1 which mitigated hepatic injury. |
abstractGer |
In this study, acetaminophen (APAP)-induced acute liver injury mice model was used to investigate the effects of C2-ceramide and oltipraz on hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase A1 (GSTA1). Notably, C2-ceramide caused alteration in mice serum transaminases and liver tissue indexes, and aggravated hepatic injury, while oltipraz alleviated hepatic injury. By screening, the optimal concentrations of C2-ceramide and oltipraz were confirmed to be 120 and 150 μmol/L, respectively. In histopathology, karyolysis and more necrotic cells and bleeding spots were appeared on administration of C2-ceramide, but only a small amount of inflammatory cells infiltration was seen after oltipraz treatment. In addition, RT-PCR and western blot results revealed that the mRNA and protein expression levels of HNF-1 and GSTA1 in liver were significantly decreased (p < 0.01) with the administration of 120 μmol/L C2-ceramide. Meanwhile, GSTA1 content in serum increased up to 1.27-fold. In contrast, 150 μmol/L oltipraz incorporation to APAP model mice resulted in obvious elevation (p < 0.01) in the mRNA and protein expression levels of HNF-1 and GSTA1 in liver, and serum GSTA1 content decreased up to 0.77-fold. In conclusion, C2-ceramide could down-regulate the expression of HNF-1 and GSTA1 which exacerbated hepatic injury, while oltipraz could up-regulate the expression of HNF-1 and GSTA1 which mitigated hepatic injury. |
abstract_unstemmed |
In this study, acetaminophen (APAP)-induced acute liver injury mice model was used to investigate the effects of C2-ceramide and oltipraz on hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase A1 (GSTA1). Notably, C2-ceramide caused alteration in mice serum transaminases and liver tissue indexes, and aggravated hepatic injury, while oltipraz alleviated hepatic injury. By screening, the optimal concentrations of C2-ceramide and oltipraz were confirmed to be 120 and 150 μmol/L, respectively. In histopathology, karyolysis and more necrotic cells and bleeding spots were appeared on administration of C2-ceramide, but only a small amount of inflammatory cells infiltration was seen after oltipraz treatment. In addition, RT-PCR and western blot results revealed that the mRNA and protein expression levels of HNF-1 and GSTA1 in liver were significantly decreased (p < 0.01) with the administration of 120 μmol/L C2-ceramide. Meanwhile, GSTA1 content in serum increased up to 1.27-fold. In contrast, 150 μmol/L oltipraz incorporation to APAP model mice resulted in obvious elevation (p < 0.01) in the mRNA and protein expression levels of HNF-1 and GSTA1 in liver, and serum GSTA1 content decreased up to 0.77-fold. In conclusion, C2-ceramide could down-regulate the expression of HNF-1 and GSTA1 which exacerbated hepatic injury, while oltipraz could up-regulate the expression of HNF-1 and GSTA1 which mitigated hepatic injury. |
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title_short |
Effects of C2-Ceramide and Oltipraz on Hepatocyte Nuclear Factor-1 and Glutathione S-Transferase A1 in Acetaminophen-Mediated Acute Mice Liver Injury |
url |
https://doi.org/10.3389/fphar.2018.01009 https://doaj.org/article/c5b1d11ccce7478e8f159e1cfe0e4ca3 https://www.frontiersin.org/article/10.3389/fphar.2018.01009/full https://doaj.org/toc/1663-9812 |
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Xin Ma Yicong Chang Yuanyuan Zhang Ishfaq Muhammad Chenxi Shi Rui Li Changwen Li Zhi Li Yuexia Lin Qing Han Fangping Liu |
author2Str |
Xin Ma Yicong Chang Yuanyuan Zhang Ishfaq Muhammad Chenxi Shi Rui Li Changwen Li Zhi Li Yuexia Lin Qing Han Fangping Liu |
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RM - Therapeutics and Pharmacology |
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doi_str |
10.3389/fphar.2018.01009 |
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up_date |
2024-07-03T17:01:19.345Z |
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