Cadmium and zinc kinetics in rat plasma following intravenous injection

Previous studies with isolated perfused rat liver suggested several hypotheses concerning Cd and Zn transport across the hepatic sinusoidal membrane. The studies presented here were designed to verify these observations in vivo. Either Cd or Zn was injected iv and plasma samples were collected for 15 min. Cd doses ranged from 0.15 to 1.48 mg/kg, Zn doses from 0.35 to 1.47 mg/kg. Cd clearance from plasma decreased from 5.29 +/- 0.69 ml/min at the lowest dose to 3.84 +/- 0.19 ml/min at the highest dose. Although Cd clearance in vivo fell within the range observed in the isolated perfused liver, at low doses Cd clearance in the isolated perfused liver was significantly above that observed in vivo. This difference is attributed to flow-limited delivery of Cd to the liver via the portal circulation in vivo. Intravenous injection of Cd doses greater than 0.30 mg/kg resulted in an elevation of plasma Zn levels; however, plateau values did not exhibit a well-defined dose-response relationship. Hepatic and renal Cd concentrations were linearly related to dose. Zn clearance from plasma was approximately one-fifth as rapid as Cd clearance. Although the liver played a dominant role in Cd clearance, accumulating 50-75% of the dose, it played a minor if not negligible role in Zn clearance. The data indicate the difficulties involved in resolving hepatic transport mechanisms in the intact animal and support the validity of the isolated perfused rat liver preparation as a system in which to investigate these mechanisms.