Experimental Porphyric Neuropathy: A Preliminary Report

Abstract

SUMMARY:An experimental model for the study of porphyric neuropathy is presented. Injection of either tetraphenylporphinesulfonate (TPPS), hematoporphyrin derivative (HpD), or delta-aminolevulinic acid (ALA) into mice resulted in markedly decreased motor nerve conduction velocity (MNCV). The MNCV returned to normal within one week following the injection of large doses of A LA, and within three weeks following the injection of close to lethal doses of HpD. hut there was no recovery of nerve function within 60 days following injection of substantially smaller doses of TPPS. Ultrastructural examination of motor nerves at various times following TPPS injection revealed the gradual development of structural abnormalities. Ultrastructional examination of the same nerves after a single dose of either A LA or Hp D failed to demonstrate any abnormalities.The present observations call for precaution as to the use of TPPS as photosensitizer in human cancer treatment.

Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model

“…Chemical porphyria, although generally used as an experimental model for understanding the porphyria disease states, has now been suggested as a novel means of endogenous sensitisation for PDT (Divaris et al, 1990). This approach involves the administration of 5-aminolaevulinic acid (ALA) which results in endogenous photosensitisation both in cultured cells (Malik & Djaldetti, 1979) and in whole animals (Sima et al, 1981). ALA is present naturally in mammalian cells since it is the first committed intermediate in the haem biosynthesis pathway.…”

Photodynamic therapy of the normal rat stomach: a comparative study between di-sulphonated aluminium phthalocyanine and 5-aminolaevulinic acid

“…In this biosynthetic pathway, the rate limiting step is that involved in the synthesis of ALA which is controlled by a regulatory feedback inhibition (Marriott, 1968;Rimington, 1966). By administering a large quantity of exogenous ALA both to in vitro systems as well as whole animals, it has been shown that the natural regulatory mechanism can become overloaded and as a result, porphyrin intermediates of the biosynthetic pathway, particularly protoporphyrin IX (PPIX), accumulate (Malik & Djaldetti, 1979;Sima et al, 1981). PPIX is a potent photosensitiser.…”

Using δ-Aminolevulinic Acid in Cancer Therapy

“…Malignant tissues usually developed much stronger fluorescence than did the adjacent normal tissues. We found that (contrary to dogma) the porphyrins in at least some of the fluorescing tissues were being synthesized in situ rather than in the liver or hemopoietic organs (23). These observations formed the basis for our subsequent studies in experimental animals, cancer patients, and human volunteers (24)(25)(26)(27)(28)(29)(30)(31).…”