3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation

Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determin...
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Autor*in:	Christopher Racine [verfasserIn] Dakota Ward [verfasserIn] Dianne K. Anestis [verfasserIn] Travis Ferguson [verfasserIn] Deborah Preston [verfasserIn] Gary O. Rankin [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2014

Schlagwörter:	3,4,5-Trichloroaniline nephrotoxicity kidney Fischer 344 rat in vitro antioxidants

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 15(2014), 11, Seite 20900-20912
Übergeordnetes Werk:	volume:15 ; year:2014 ; number:11 ; pages:20900-20912

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/ijms151120900

Katalog-ID:	DOAJ070779236

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allfields	10.3390/ijms151120900 doi (DE-627)DOAJ070779236 (DE-599)DOAJ79de3c897d514af08fe263f1397c7482 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Christopher Racine verfasserin aut 3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a cytochrome P450 (CYP), flavin monooxygenase (FMO), cyclooxygenase or peroxidase inhibitor prior to incubation with dimethyl sulfoxide (control) or TCA (0.5 mM) for 120 min. At 60 min, TCA did not induce cytotoxicity, but induced cytotoxicity as early as 90 min with 0.5 mM or higher TCA and at 120 min with 0.1 mM or higher TCA, as evidenced by increased lactate dehydrogenase (LDH) release. Pretreatment with the CYP inhibitor piperonyl butoxide, the cyclooxygenase inhibitor indomethacin or the peroxidase inhibitor mercaptosuccinate attenuated TCA cytotoxicity, while pretreatment with FMO inhibitors or the CYP inhibitor metyrapone had no effect on TCA nephrotoxicity. Pretreatment with an antioxidant (α-tocopherol, glutathione, ascorbate or N-acetyl-l-cysteine) also reduced or completely blocked TCA cytotoxicity. These results indicate that TCA is directly nephrotoxic to IRCC in a time and concentration dependent manner. Bioactivation of TCA to toxic metabolites by CYP, cyclooxygenase and/or peroxidase contributes to the mechanism of TCA nephrotoxicity. Lastly, free radicals play a role in TCA cytotoxicity, although the exact nature of the origin of these radicals remains to be determined. 3,4,5-Trichloroaniline nephrotoxicity kidney Fischer 344 rat in vitro antioxidants Biology (General) Chemistry Dakota Ward verfasserin aut Dianne K. Anestis verfasserin aut Travis Ferguson verfasserin aut Deborah Preston verfasserin aut Gary O. Rankin verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 15(2014), 11, Seite 20900-20912 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:15 year:2014 number:11 pages:20900-20912 https://doi.org/10.3390/ijms151120900 kostenfrei https://doaj.org/article/79de3c897d514af08fe263f1397c7482 kostenfrei http://www.mdpi.com/1422-0067/15/11/20900 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_70 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_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2014 11 20900-20912
spelling	10.3390/ijms151120900 doi (DE-627)DOAJ070779236 (DE-599)DOAJ79de3c897d514af08fe263f1397c7482 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Christopher Racine verfasserin aut 3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a cytochrome P450 (CYP), flavin monooxygenase (FMO), cyclooxygenase or peroxidase inhibitor prior to incubation with dimethyl sulfoxide (control) or TCA (0.5 mM) for 120 min. At 60 min, TCA did not induce cytotoxicity, but induced cytotoxicity as early as 90 min with 0.5 mM or higher TCA and at 120 min with 0.1 mM or higher TCA, as evidenced by increased lactate dehydrogenase (LDH) release. Pretreatment with the CYP inhibitor piperonyl butoxide, the cyclooxygenase inhibitor indomethacin or the peroxidase inhibitor mercaptosuccinate attenuated TCA cytotoxicity, while pretreatment with FMO inhibitors or the CYP inhibitor metyrapone had no effect on TCA nephrotoxicity. Pretreatment with an antioxidant (α-tocopherol, glutathione, ascorbate or N-acetyl-l-cysteine) also reduced or completely blocked TCA cytotoxicity. These results indicate that TCA is directly nephrotoxic to IRCC in a time and concentration dependent manner. Bioactivation of TCA to toxic metabolites by CYP, cyclooxygenase and/or peroxidase contributes to the mechanism of TCA nephrotoxicity. Lastly, free radicals play a role in TCA cytotoxicity, although the exact nature of the origin of these radicals remains to be determined. 3,4,5-Trichloroaniline nephrotoxicity kidney Fischer 344 rat in vitro antioxidants Biology (General) Chemistry Dakota Ward verfasserin aut Dianne K. Anestis verfasserin aut Travis Ferguson verfasserin aut Deborah Preston verfasserin aut Gary O. Rankin verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 15(2014), 11, Seite 20900-20912 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:15 year:2014 number:11 pages:20900-20912 https://doi.org/10.3390/ijms151120900 kostenfrei https://doaj.org/article/79de3c897d514af08fe263f1397c7482 kostenfrei http://www.mdpi.com/1422-0067/15/11/20900 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_70 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_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2014 11 20900-20912
allfields_unstemmed	10.3390/ijms151120900 doi (DE-627)DOAJ070779236 (DE-599)DOAJ79de3c897d514af08fe263f1397c7482 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Christopher Racine verfasserin aut 3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a cytochrome P450 (CYP), flavin monooxygenase (FMO), cyclooxygenase or peroxidase inhibitor prior to incubation with dimethyl sulfoxide (control) or TCA (0.5 mM) for 120 min. At 60 min, TCA did not induce cytotoxicity, but induced cytotoxicity as early as 90 min with 0.5 mM or higher TCA and at 120 min with 0.1 mM or higher TCA, as evidenced by increased lactate dehydrogenase (LDH) release. Pretreatment with the CYP inhibitor piperonyl butoxide, the cyclooxygenase inhibitor indomethacin or the peroxidase inhibitor mercaptosuccinate attenuated TCA cytotoxicity, while pretreatment with FMO inhibitors or the CYP inhibitor metyrapone had no effect on TCA nephrotoxicity. Pretreatment with an antioxidant (α-tocopherol, glutathione, ascorbate or N-acetyl-l-cysteine) also reduced or completely blocked TCA cytotoxicity. These results indicate that TCA is directly nephrotoxic to IRCC in a time and concentration dependent manner. Bioactivation of TCA to toxic metabolites by CYP, cyclooxygenase and/or peroxidase contributes to the mechanism of TCA nephrotoxicity. Lastly, free radicals play a role in TCA cytotoxicity, although the exact nature of the origin of these radicals remains to be determined. 3,4,5-Trichloroaniline nephrotoxicity kidney Fischer 344 rat in vitro antioxidants Biology (General) Chemistry Dakota Ward verfasserin aut Dianne K. Anestis verfasserin aut Travis Ferguson verfasserin aut Deborah Preston verfasserin aut Gary O. Rankin verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 15(2014), 11, Seite 20900-20912 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:15 year:2014 number:11 pages:20900-20912 https://doi.org/10.3390/ijms151120900 kostenfrei https://doaj.org/article/79de3c897d514af08fe263f1397c7482 kostenfrei http://www.mdpi.com/1422-0067/15/11/20900 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_70 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_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2014 11 20900-20912
allfieldsGer	10.3390/ijms151120900 doi (DE-627)DOAJ070779236 (DE-599)DOAJ79de3c897d514af08fe263f1397c7482 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Christopher Racine verfasserin aut 3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a cytochrome P450 (CYP), flavin monooxygenase (FMO), cyclooxygenase or peroxidase inhibitor prior to incubation with dimethyl sulfoxide (control) or TCA (0.5 mM) for 120 min. At 60 min, TCA did not induce cytotoxicity, but induced cytotoxicity as early as 90 min with 0.5 mM or higher TCA and at 120 min with 0.1 mM or higher TCA, as evidenced by increased lactate dehydrogenase (LDH) release. Pretreatment with the CYP inhibitor piperonyl butoxide, the cyclooxygenase inhibitor indomethacin or the peroxidase inhibitor mercaptosuccinate attenuated TCA cytotoxicity, while pretreatment with FMO inhibitors or the CYP inhibitor metyrapone had no effect on TCA nephrotoxicity. Pretreatment with an antioxidant (α-tocopherol, glutathione, ascorbate or N-acetyl-l-cysteine) also reduced or completely blocked TCA cytotoxicity. These results indicate that TCA is directly nephrotoxic to IRCC in a time and concentration dependent manner. Bioactivation of TCA to toxic metabolites by CYP, cyclooxygenase and/or peroxidase contributes to the mechanism of TCA nephrotoxicity. Lastly, free radicals play a role in TCA cytotoxicity, although the exact nature of the origin of these radicals remains to be determined. 3,4,5-Trichloroaniline nephrotoxicity kidney Fischer 344 rat in vitro antioxidants Biology (General) Chemistry Dakota Ward verfasserin aut Dianne K. Anestis verfasserin aut Travis Ferguson verfasserin aut Deborah Preston verfasserin aut Gary O. Rankin verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 15(2014), 11, Seite 20900-20912 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:15 year:2014 number:11 pages:20900-20912 https://doi.org/10.3390/ijms151120900 kostenfrei https://doaj.org/article/79de3c897d514af08fe263f1397c7482 kostenfrei http://www.mdpi.com/1422-0067/15/11/20900 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_70 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_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2014 11 20900-20912
allfieldsSound	10.3390/ijms151120900 doi (DE-627)DOAJ070779236 (DE-599)DOAJ79de3c897d514af08fe263f1397c7482 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Christopher Racine verfasserin aut 3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a cytochrome P450 (CYP), flavin monooxygenase (FMO), cyclooxygenase or peroxidase inhibitor prior to incubation with dimethyl sulfoxide (control) or TCA (0.5 mM) for 120 min. At 60 min, TCA did not induce cytotoxicity, but induced cytotoxicity as early as 90 min with 0.5 mM or higher TCA and at 120 min with 0.1 mM or higher TCA, as evidenced by increased lactate dehydrogenase (LDH) release. Pretreatment with the CYP inhibitor piperonyl butoxide, the cyclooxygenase inhibitor indomethacin or the peroxidase inhibitor mercaptosuccinate attenuated TCA cytotoxicity, while pretreatment with FMO inhibitors or the CYP inhibitor metyrapone had no effect on TCA nephrotoxicity. Pretreatment with an antioxidant (α-tocopherol, glutathione, ascorbate or N-acetyl-l-cysteine) also reduced or completely blocked TCA cytotoxicity. These results indicate that TCA is directly nephrotoxic to IRCC in a time and concentration dependent manner. Bioactivation of TCA to toxic metabolites by CYP, cyclooxygenase and/or peroxidase contributes to the mechanism of TCA nephrotoxicity. Lastly, free radicals play a role in TCA cytotoxicity, although the exact nature of the origin of these radicals remains to be determined. 3,4,5-Trichloroaniline nephrotoxicity kidney Fischer 344 rat in vitro antioxidants Biology (General) Chemistry Dakota Ward verfasserin aut Dianne K. Anestis verfasserin aut Travis Ferguson verfasserin aut Deborah Preston verfasserin aut Gary O. Rankin verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 15(2014), 11, Seite 20900-20912 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:15 year:2014 number:11 pages:20900-20912 https://doi.org/10.3390/ijms151120900 kostenfrei https://doaj.org/article/79de3c897d514af08fe263f1397c7482 kostenfrei http://www.mdpi.com/1422-0067/15/11/20900 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_70 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_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 15 2014 11 20900-20912
language	English
source	In International Journal of Molecular Sciences 15(2014), 11, Seite 20900-20912 volume:15 year:2014 number:11 pages:20900-20912
sourceStr	In International Journal of Molecular Sciences 15(2014), 11, Seite 20900-20912 volume:15 year:2014 number:11 pages:20900-20912
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	3,4,5-Trichloroaniline nephrotoxicity kidney Fischer 344 rat in vitro antioxidants Biology (General) Chemistry
isfreeaccess_bool	true
container_title	International Journal of Molecular Sciences
authorswithroles_txt_mv	Christopher Racine @@aut@@ Dakota Ward @@aut@@ Dianne K. Anestis @@aut@@ Travis Ferguson @@aut@@ Deborah Preston @@aut@@ Gary O. Rankin @@aut@@
publishDateDaySort_date	2014-01-01T00:00:00Z
hierarchy_top_id	316340715
id	DOAJ070779236
language_de	englisch
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callnumber-first	Q - Science
author	Christopher Racine
spellingShingle	Christopher Racine misc QH301-705.5 misc QD1-999 misc 3,4,5-Trichloroaniline misc nephrotoxicity misc kidney misc Fischer 344 rat misc in vitro misc antioxidants misc Biology (General) misc Chemistry 3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation
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topic_title	QH301-705.5 QD1-999 3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation 3,4,5-Trichloroaniline nephrotoxicity kidney Fischer 344 rat in vitro antioxidants
topic	misc QH301-705.5 misc QD1-999 misc 3,4,5-Trichloroaniline misc nephrotoxicity misc kidney misc Fischer 344 rat misc in vitro misc antioxidants misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc 3,4,5-Trichloroaniline misc nephrotoxicity misc kidney misc Fischer 344 rat misc in vitro misc antioxidants misc Biology (General) misc Chemistry
topic_browse	misc QH301-705.5 misc QD1-999 misc 3,4,5-Trichloroaniline misc nephrotoxicity misc kidney misc Fischer 344 rat misc in vitro misc antioxidants misc Biology (General) misc Chemistry
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title	3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation
ctrlnum	(DE-627)DOAJ070779236 (DE-599)DOAJ79de3c897d514af08fe263f1397c7482
title_full	3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation
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journal	International Journal of Molecular Sciences
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author_browse	Christopher Racine Dakota Ward Dianne K. Anestis Travis Ferguson Deborah Preston Gary O. Rankin
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author-letter	Christopher Racine
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title_sort	3,4,5-trichloroaniline nephrotoxicity in vitro: potential role of free radicals and renal biotransformation
callnumber	QH301-705.5
title_auth	3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation
abstract	Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a cytochrome P450 (CYP), flavin monooxygenase (FMO), cyclooxygenase or peroxidase inhibitor prior to incubation with dimethyl sulfoxide (control) or TCA (0.5 mM) for 120 min. At 60 min, TCA did not induce cytotoxicity, but induced cytotoxicity as early as 90 min with 0.5 mM or higher TCA and at 120 min with 0.1 mM or higher TCA, as evidenced by increased lactate dehydrogenase (LDH) release. Pretreatment with the CYP inhibitor piperonyl butoxide, the cyclooxygenase inhibitor indomethacin or the peroxidase inhibitor mercaptosuccinate attenuated TCA cytotoxicity, while pretreatment with FMO inhibitors or the CYP inhibitor metyrapone had no effect on TCA nephrotoxicity. Pretreatment with an antioxidant (α-tocopherol, glutathione, ascorbate or N-acetyl-l-cysteine) also reduced or completely blocked TCA cytotoxicity. These results indicate that TCA is directly nephrotoxic to IRCC in a time and concentration dependent manner. Bioactivation of TCA to toxic metabolites by CYP, cyclooxygenase and/or peroxidase contributes to the mechanism of TCA nephrotoxicity. Lastly, free radicals play a role in TCA cytotoxicity, although the exact nature of the origin of these radicals remains to be determined.
abstractGer	Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a cytochrome P450 (CYP), flavin monooxygenase (FMO), cyclooxygenase or peroxidase inhibitor prior to incubation with dimethyl sulfoxide (control) or TCA (0.5 mM) for 120 min. At 60 min, TCA did not induce cytotoxicity, but induced cytotoxicity as early as 90 min with 0.5 mM or higher TCA and at 120 min with 0.1 mM or higher TCA, as evidenced by increased lactate dehydrogenase (LDH) release. Pretreatment with the CYP inhibitor piperonyl butoxide, the cyclooxygenase inhibitor indomethacin or the peroxidase inhibitor mercaptosuccinate attenuated TCA cytotoxicity, while pretreatment with FMO inhibitors or the CYP inhibitor metyrapone had no effect on TCA nephrotoxicity. Pretreatment with an antioxidant (α-tocopherol, glutathione, ascorbate or N-acetyl-l-cysteine) also reduced or completely blocked TCA cytotoxicity. These results indicate that TCA is directly nephrotoxic to IRCC in a time and concentration dependent manner. Bioactivation of TCA to toxic metabolites by CYP, cyclooxygenase and/or peroxidase contributes to the mechanism of TCA nephrotoxicity. Lastly, free radicals play a role in TCA cytotoxicity, although the exact nature of the origin of these radicals remains to be determined.
abstract_unstemmed	Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a cytochrome P450 (CYP), flavin monooxygenase (FMO), cyclooxygenase or peroxidase inhibitor prior to incubation with dimethyl sulfoxide (control) or TCA (0.5 mM) for 120 min. At 60 min, TCA did not induce cytotoxicity, but induced cytotoxicity as early as 90 min with 0.5 mM or higher TCA and at 120 min with 0.1 mM or higher TCA, as evidenced by increased lactate dehydrogenase (LDH) release. Pretreatment with the CYP inhibitor piperonyl butoxide, the cyclooxygenase inhibitor indomethacin or the peroxidase inhibitor mercaptosuccinate attenuated TCA cytotoxicity, while pretreatment with FMO inhibitors or the CYP inhibitor metyrapone had no effect on TCA nephrotoxicity. Pretreatment with an antioxidant (α-tocopherol, glutathione, ascorbate or N-acetyl-l-cysteine) also reduced or completely blocked TCA cytotoxicity. These results indicate that TCA is directly nephrotoxic to IRCC in a time and concentration dependent manner. Bioactivation of TCA to toxic metabolites by CYP, cyclooxygenase and/or peroxidase contributes to the mechanism of TCA nephrotoxicity. Lastly, free radicals play a role in TCA cytotoxicity, although the exact nature of the origin of these radicals remains to be determined.
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title_short	3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation
url	https://doi.org/10.3390/ijms151120900 https://doaj.org/article/79de3c897d514af08fe263f1397c7482 http://www.mdpi.com/1422-0067/15/11/20900 https://doaj.org/toc/1422-0067
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