N-(4-HYDROXYPHENYL)RETINAMIDE (FENRETINIDE) INDUCES RETINOL-BINDING PROTEIN SECRETION FROM LIVER AND ACCUMULATION IN THE KIDNEYS IN RATS

The chemopreventive retinoid N-(4-hydroxyphenyl)retinamide (HPR) depresses serum retinol and retinol-binding protein (RBP) concentrations. To study long-term effects of HPR on serum proteins, rats were fed a control diet or a diet containing HPR (737 mumol/kg diet) for 14 d. Serum retinol and RBP of HPR-treated rats decreased to 42 and 41%, respectively, of initial concentrations. Transthyretin, albumin and transferrin did not differ between treatments. Previous studies found that HPR decreased secretion of the retinol-RBP complex into plasma. To investigate acute effects of HPR on RBP metabolism, vitamin A-deficient rats were injected with HPR (51 mumol/kg body wt), retinol (0.52 mumol/rat) or Tween carrier only. Liver RBP concentrations in HPR- and retinol-treated rats were 45 and 18%, respectively, of concentrations in Tween-treated rats, indicating rapid RBP secretion. Tween- and HPR-treated rats maintained relatively constant serum RBP concentrations, whereas retinol-replete rats had 12-fold higher serum RBP after 150 min. Rats treated with HPR and rats treated with retinol had 29- and eightfold higher kidney RBP concentrations, respectively, than Tween-treated rats, indicating rapid clearance of RBP from plasma. We conclude that HPR affects RBP metabolism by inducing secretion of liver RBP into the bloodstream and rapid RBP accumulation in the kidney.