Alterations of xenobiotic excretory function induced by potassium dichromate or carbon tetrachloride pretreatment

Biliary and urinary excretory functions were determined in animals pretreated with a hepatotoxin (CCl4) or a nephrotoxin (K2Cr2O7), using polar metabolites of imipramine (PMIMP) and digoxin as models for anionic and neutral transport systems. Biliary excretion of PMIMP was decreased in CCl4-treated rats; urinary excretion was increased. Urinary and biliary excretion of digoxin were both unaffected by CCl4 treatment, but accumulation of digoxin by liver was impaired. K2Cr2O7 treatment resulted in severe nephrotoxicity accompanied by decreased urinary excretion of both model compounds. Hepatic excretion of digoxin, but not PMIMP, was increased in these animals. With minimal nephrotoxicity, urinary excretion of both compounds was unaffected. Thus the effect of toxicity on hepatic or renal excretion depends on the properties of the compounds used for excretion studies. In addition, for compounds excreted by both routes, impaired excretion by one route may be accompanied by increased excretion by the other. The extent of this compensatory mechanism may depend on several factors including the physiochemical properties of the compounds and the degree to which they are excreted by each route normally. In addition, specific cellular transport mechanisms may be important factors if involved in the excretory events.