NEUROTOXICITY OF TETRAPHENYLPORPHINESULFONATE TPPS4 and ITS RELATION TO PHOTODYNAMIC THERAPY*

Abstract Tetraphenylporphinesulfonate (TPPS₄) is a synthetic porphyrin that localizes in certain tumors to a higher absolute concentration and with more favorable tumor to other tissue ratios than any other porphyrin yet studied. Its utilization for photodynamic therapy and other applications has been inhibited by reported neurotoxicity. We injected TPPS₄ over a broad dose range of 5-150 mg kg^?1 and observed the effects on peripheral nerve in groups of animals sacrificed 35, 70 and 140 days later. No immediate deaths or phototoxic manifestations were seen. Light and electron microscopy, however, revealed cytoskeletal abnormalities and nerve fiber degeneration affecting both myelinated and unmyelinated fibers in all the time and dose groups. These findings have similarities to those of other experimental toxic neuropathies, and may also be related to the preponderance of autonomic manifestations in patients with porphyric neuropathy. The morphological changes consisted of tangles of fibrillar material in the myelinated fibers and loss of neurotubules in the unmyelinated fibers. Our studies indicate a direct interaction of TPPS₄ with tubulin. This biological mechanism may be involved in the selective distribution of certain parenterally administered porphyrins.