Trichlorophenol Induced Nephrotoxicity in Isolated Rat Renal Cortical Cells

Trichlorophenols (TCPs) are wood preservatives and intermediates in the synthesis of numerous pesticides. They appear in the environment as manufacturing byproducts and during the chlorination of drinking and waste water. TCPs are also metabolites of chlorinated compounds, such as chlorobenzenes and chlorophenoxy acids. Aquatic toxicity induced by these compounds has been studied in some detail, but few studies have focused on mammalian toxicity. The purpose of this study was to examine the nephrotoxic potential of four TCPs (2,3,4-; 2,3,6-, 2,4,5-; and 2,4,6-TCP) in an in vitro model using isolated renal cortical cells (IRCC) from male Fischer 344 rats. IRCC (~4 million cells/ml; 3 ml) were incubated with shaking at 37°C under a 95% oxygen/5% carbon dioxide atmosphere with a TCP (0 – 1.0 mM) or vehicle (dimethyl sulfoxide) for 60 min. General cytotoxicity was determined by assessing trypan blue exclusion of IRCC, measuring changes in lactate dehydrogenase (LDH) release, and quantitating ATP levels. LDH release was increased only at 1.0 mM for 2,3,6- and 2,4,6-TCP. 2,3,4-TCP increased LDH release at 0.5 mM or greater concentrations. However, 2,4,5-TCP increased LDH release at 0.1 mM or greater concentrations. ATP levels were decreased at 1.0 mM for all compounds, at 0.5 mM for 2,3,4-TCP and at all 2,4,5-TCP concentrations. Therefore, the general order of decreasing nephrotoxic potential was 2,4,5-TCP > 2,3,4-TCP >2,3,6- and 2,4,6-TCP. Support or Funding Information Supported in part by NIH grant P20GM103434. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.