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Int. J. Mol. Sci. 2017, 18(6), 1165; doi:10.3390/ijms18061165

Role of Free Radicals and Biotransformation in Trichloronitrobenzene-Induced Nephrotoxicity In Vitro

Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA
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Academic Editor: Guido R.M.M. Haenen
Received: 17 March 2017 / Revised: 12 May 2017 / Accepted: 24 May 2017 / Published: 31 May 2017
(This article belongs to the Special Issue Nephrotoxicity)
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Abstract

This study determined the comparative nephrotoxic potential of four trichloronitrobenzenes (TCNBs) (2,3,4-; 2,4,5-; 2,4,6-; and 3,4,5-TCNB) and explored the effects of antioxidants and biotransformation inhibitors on TCNB-induced cytotoxicity in isolated renal cortical cells (IRCC) from male Fischer 344 rats. IRCC were incubated with a TCNB up to 1.0 mM for 15–120 min. Pretreatment with an antioxidant or cytochrome P450 (CYP), flavin monooxygenase (FMO), or peroxidase inhibitor was used in some experiments. Among the four TCNBs, the order of decreasing nephrotoxic potential was approximately 3,4,5- > 2,4,6- > 2,3,4- > 2,4,5-TCNB. The four TCNBs exhibited a similar profile of attenuation of cytotoxicity in response to antioxidant pretreatments. 2,3,4- and 3,4,5-TCNB cytotoxicity was attenuated by most of the biotransformation inhibitors tested, 2,4,5-TCNB cytotoxicity was only inhibited by isoniazid (CYP 2E1 inhibitor), and 2,4,6-TCNB-induced cytotoxicity was inhibited by one CYP inhibitor, one FMO inhibitor, and one peroxidase inhibitor. All of the CYP specific inhibitors tested offered some attenuation of 3,4,5-TCNB cytotoxicity. These results indicate that 3,4,5-TCNB is the most potent nephrotoxicant, free radicals play a role in the TCNB cytotoxicity, and the role of biotransformation in TCNB nephrotoxicity in vitro is variable and dependent on the position of the chloro groups. View Full-Text
Keywords: trichloronitrobenzenes; nephrotoxicity; in vitro; antioxidants; biotransformation trichloronitrobenzenes; nephrotoxicity; in vitro; antioxidants; biotransformation
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MDPI and ACS Style

Rankin, G.O.; Tyree, C.; Pope, D.; Tate, J.; Racine, C.; Anestis, D.K.; Brown, K.C.; Dial, M.; Valentovic, M.A. Role of Free Radicals and Biotransformation in Trichloronitrobenzene-Induced Nephrotoxicity In Vitro. Int. J. Mol. Sci. 2017, 18, 1165.

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