The pharmacokinetics of fluorescein isothiocyanate (FITC)-labeled human immunoglobulin G (FITC-hIgG) were investigated in mice treated with or without cisplatin, cis-diamminedichloroplatinum (II) (CDDP). When FITC-hIgG was intravenously injected into normal mice, FITC-hIgG disappeared from the plasma with a half-life of 7.4 days, which was similar to the previously reported half-life of mouse IgG in mice. Next, we examined the effect of CDDP administration on the disappearance of plasma FITC-hIgG in mice. Treatment with CDDP (5 mg/kg) followed by FITC-hIgG injection enhanced the levels of blood urea nitrogen and kidney injury molecule-1 (Kim-1) mRNA expression in the kidney, showing induction of acute kidney injury. The plasma concentration-time profile of FITC-hIgG in mice treated with CDDP was similar to that in normal mice. On the other hand, the accumulation of FITC-hIgG in the kidney was significantly enhanced by CDDP administration. The renal mRNA level of neonatal Fc receptor (FcRn) was not affected by CDDP administration, whereas those of megalin and cubilin, endocytic receptors abundantly expressed in the renal proximal tubule, were increased. These observations suggest that acute kidney injury might have little effect on the plasma level of IgG, while renal accumulation of IgG might be increased during CDDP-induced acute kidney injury.
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