A major clinical complication of an acute attack of porphyria is severe peripheral neuropathy. In the course of porphyria research, many experimental porphyrias have been developed, including PBG-DE deficient mice and ferrochelatase deficient mice. At this Institute, we are still using old fashioned in vivo models - animals treated with an inhibitor of heme biosynthesis. Next, we will present some results obtained in mice treated with a competitive inhibitor of protoporphyrinogen oxidase , which form a basis for our porphyria pathophysiology theory. Treatment of mice with oxadiazon, an inhibitor of protoporphyrinogen oxidase, produces a dose-related inhibition of the liver enzyme.
Liver contains elevated amounts of protoporphyrinogen, the colourless precursor of protoporphyrin.
Interestingly, at high oxadiazon concentrations, we observed porphyrin fluorescence in the peripheral nerves. The liver is an exception, due to its high demand for cytochrome P450 and tryptophan pyrrolase heme. The excess precursor production by the liver, and consequent conversion to porphyrins in other organs, is a key to the whole story. There are sporadic autopsy reports describing fluorescence in the peripheral nerves of porphyria patients. There is also one paper on increased trigeminal nerve porphyrin content in DDC-induced porphyria.