Nephrotoxic interactions between ketonic solvents and halogenated aliphatic chemicals

Recent studies have indicated that (1) ketonic solvents and ketogenic chemicals can potentiate the nephrotoxic and hepatotoxic effects of one or more halogenated hydrocarbons; and (2) the relative ability of ketones to potentiate the liver injury produced by chloroform (CHCl3) may be influenced by the carbon skeleton length of the ketone. Although five ketones (acetone, 2-butanone, 2-pentanone, 2-hexanone, (HX), and 2-heptanone) increased CHCl3-induced kidney and liver injury in male, Fischer 344 rats, no relationship between ketone chain length and potentiating capacity was observed. HX potentiated the CHCL3-induced depletion of hepatic glutathione content and increased the irreversible binding of 14CHCl3-derived radiolabel to hepatic constituents. In contrast, CHCl3 did not alter glutathione content in the renal cortex of either vehicle- or HX-pretreated rats. Although HX increased the binding of 14C from 14CHCl3 to renal cortical macromolecules, the magnitude of the increase was unremarkable, approaching only the extent of hepatic 14C binding in vehicle-pretreated rats challenged with 14CHCl3. Since the severity of renal and hepatic injury was comparable in rats receiving the combination of HX + CHCl3, it appeared that HX potentiated CHCl3 nephro- and hepatotoxicity by different mechanisms. Ketone pretreatment did not potentiate the renal injury produced by potassium dichromate or hexachloro-1,3-butadiene.