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3,4‐Dichloronitrobenzene and 1,2,3‐trichloro‐5‐nitrobenzene in vitro nephrotoxicity in isolated rat renal cortical cells
Author(s) -
Rankin Gary O'Neal,
Greene Brittany,
Schuetz Carly,
Anestis Dianne
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.968.6
Subject(s) - nephrotoxicity , piperonyl butoxide , chemistry , glutathione , toxicity , pharmacology , kidney , biochemistry , antioxidant , medicine , endocrinology , biology , enzyme , organic chemistry
Chloronitrobenzene (CNB) compounds are important chemical intermediates in the manufacture of dyes, drugs and agricultural chemicals. Some CNBs induce nephrotoxicity in animal models and human kidney cells in vitro. In this study, isolated renal cortical cells (IRCC) from male Fischer 344 rats were used to examine the nephrotoxic potential of two CNBs and to examine if the nephrotoxicity resulted from the formation of metabolites. Nephrotoxic potential was assessed by incubating 3,4‐dichloronitrobenzene (3,4‐DCNB) or 1,2,3‐trichloro‐5‐nitrobenzene (1,2,3 ‐TC5NB) at concentrations of 0 – 1.0 mM with IRCC (4 x 106 cells/ml) for 30 or 60 minutes and measuring lactate dehydrogenase (LDH) release. In some experiments, cells were pretreated with a cytochrome P450 inhibitor [piperonyl butoxide or metyrapone (1.0 mM)] or an antioxidant [glutathione (1.0mM), á‐tocopherol (1.0 mM), or ascorbate (2.0 mM)] followed by 0.5 mM 3, 4‐DCNB and 1, 2, 3‐TC5NB. Nephrotoxicity was induced by both CNBs (0.25 mM or higher) as early as 30 min. All antioxidant pretreatments reduced toxicity, suggesting that free radicals participate in the mechanism of CNB‐induced nephrotoxicity, while piperonyl butoxide and metyrapone attenuation of toxicity indicates metabolites play a role in the nephrotoxic mechanism. Supported by NIH Grant 3P20RR016477 to the West Virginia IDeA Network for Biomedical Research Excellence.