EFFECTS OF DIFFERENTIAL CHANGES IN RAT HEPATIC AND RENAL CYTOCHROME-P-450 CONCENTRATIONS ON HEPATOTOXICITY AND NEPHROTOXICITY OF CHLOROFORM

  • 1 January 1981
    • journal article
    • research article
    • Vol. 31  (1) , 99-110
Abstract
Cytochrome P-450 concentrations in rat liver and kidney were differentially altered by pretreatment with phenobarbital (PB), Cd or fasting. The rats were then challenged with CHCl3. Hepatotoxicity was assayed by alanine aminotransferase activity (AlaAT), the nephrotoxicity by inhibition of p-aminohippuric acid (PAH) uptake in vitro, and both by histopathology. Fasting increased renal and hepatic cytochromes P-450 and CHCl3-mediated necrosis in both organs. PB induction increased and Cd decreased the liver cytochrome P-450 concentrations and the hepatotoxicity mediated by CHCl3. PB and Cd had no effect on renal cytochrome P-450 concentrations or CHCl3 nephrotoxicity. The nephrotoxic metabolite of CHCl3 is probably produced within the kidney and the hepatotoxic metabolite in the liver. [CHCl3, a chlorine-treated water contaminant, is a suspected carcinogen.].