Uptake and localisation of haematoporphyrin derivative in normal rat liver

Fluorescence microscopy and analytical subcellular fractionation were used to investigate the hepatic localisation of haematoporphyrin derivative (HPD) after intraperitoneal administration. HPD was found to rapidly accumulate in the liver and then to slowly decline over 48 hr. Fluorescence microscopy showed that although at early times porphyrins could not be localised to a particular cell type, at 24 hr porphyrins were preferentially localised to the Kupffer cells of the liver. Subcellular fractionation studies indicated that the initial rapid uptake of HPD was to the cytosol. However, at 24 hr, porphyrins appeared to be localised to lysosomes. Lysosomal localisation was confirmed using the selective organelle perturbant, Triton WR 1339. No evidence was found either at the light microscope level or by subcellular fractionation to suggest association of HPD with other organelles. HPLC analysis showed that the porphyrins present in the plasma and in the cytosol and lysosome fractions were mainly the (RS, SR) and (RR, SS) diastereoisomers of haematoporphyrin and the two position isomers 8-(1-hydroxyethyl)-3-vinyldeuteroporphyrin and 3-(1-hydroxyethyl)-8-vinyldeuteroporphyrin. There was no evidence for the involvement of dimers such as dihaematoporphyrin ether.