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Oxidative Stress Induced Following Exposure to 3,5‐Dichloroaniline (3,5‐DCA) In Vitro: Role in Nephrotoxicity
Author(s) -
Racine Christopher,
Anestis Dianne,
Ball John,
Valentovic Monica,
Rankin Gary
Publication year - 2015
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.29.1_supplement.938.7
Subject(s) - nephrotoxicity , oxidative stress , chemistry , glutathione , pharmacology , in vivo , in vitro , biochemistry , toxicity , enzyme , medicine , biology , organic chemistry , microbiology and biotechnology
Anilines and their chlorinated derivatives are used in the production of a wide variety of agricultural products, drugs and dyes. Studies have shown that chlorinated aniline exposure leads to nephrotoxicity in both in vitro and in vivo models. Of the mono‐ and dichloroanilines studied, 3,5‐dichloroaniline (3,5‐DCA) proved to posses the most nephrotoxic potential. Exposure to 1.0 mM 3,5‐DCA for 90 min significantly increased LDH release in isolated renal cortical cells (IRCC) from male Fischer 344 rats. Pretreatment of IRCC with antioxidants significantly attenuated LDH release, suggesting that free radical/oxidative stress mechanisms may play a role in 3,5‐DCA induced nephrotoxicity. The purpose of the current study was to explore the potential role of oxidative stress in 3,5‐DCA nephrotoxicity in vitro. IRCC (4 x 10 6 cells/ml; 3 ml) were exposed to 3,5‐DCA (0, 0.5, or 1.0 mM) for either 60 or 90 min. Aliquots were then taken for LDH release assays, protein carbonyl detection using Oxyblot kits from Millipore, and glutathione (GSH and GSSG) determination assays. Protein carbonyls were significantly increased following exposure to 1.0 mM 3,5‐DCA after 90 min only, while a shift in the ratio of GSSG/GSH was seen at exposure to 1.0 mM 3,5‐DCA for 60 min. However, in both cases the increase in oxidative stress markers occurred after there was a significant increase in LDH release. These findings suggest that despite 3,5‐DCA's ability to induce oxidative stress, oxidative stress is not an early initiator of 3,5‐DCA nephrotoxicity in IRCC. These studies were supported, in part, by NIH grant P20GM103434.