Hostname: page-component-848d4c4894-hfldf Total loading time: 0 Render date: 2024-05-09T13:24:42.194Z Has data issue: false hasContentIssue false

Experimental Porphyric Neuropathy: A Preliminary Report

Published online by Cambridge University Press:  18 September 2015

Anders A.F. Sima*
Affiliation:
Department of Pathology, Division of Neuropathology, Toronto General Hospital and University of Toronto, Toronto, Ontario, Canada; and Departments of Pathology and Radiation Oncology, Kingston General Hospital and Queen’s University, Kingston, Ontario, Canada
James C. Kennedy*
Affiliation:
Department of Pathology, Division of Neuropathology, Toronto General Hospital and University of Toronto, Toronto, Ontario, Canada; and Departments of Pathology and Radiation Oncology, Kingston General Hospital and Queen’s University, Kingston, Ontario, Canada
Dennis Blakeslee*
Affiliation:
Department of Pathology, Division of Neuropathology, Toronto General Hospital and University of Toronto, Toronto, Ontario, Canada; and Departments of Pathology and Radiation Oncology, Kingston General Hospital and Queen’s University, Kingston, Ontario, Canada
David M. Robertson*
Affiliation:
Department of Pathology, Division of Neuropathology, Toronto General Hospital and University of Toronto, Toronto, Ontario, Canada; and Departments of Pathology and Radiation Oncology, Kingston General Hospital and Queen’s University, Kingston, Ontario, Canada
*
Department of Pathology, Division of Neuropathology, Banting Institute, 100 College Street, Toronto, Ontario, M5G 11.5, Canada
Department of Pathology, Division of Neuropathology, Banting Institute, 100 College Street, Toronto, Ontario, M5G 11.5, Canada
Department of Pathology, Division of Neuropathology, Banting Institute, 100 College Street, Toronto, Ontario, M5G 11.5, Canada
Department of Pathology, Division of Neuropathology, Banting Institute, 100 College Street, Toronto, Ontario, M5G 11.5, Canada
Rights & Permissions [Opens in a new window]

Summary:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

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.

Type
Articles
Copyright
Copyright © Canadian Neurological Sciences Federation 1981

References

Anzil, A.P., Dozic, S.: (1978) Peripheral nerve changes in porphyric neuropathy. Findings in a sural nerve biopsy. Acta Neuropathol. 42. 121126.CrossRefGoogle Scholar
Bacchus, H.: (1976) Essentials of metabolic diseases and endocrinology, pp. 235253. University Park Press, Baltimore.Google Scholar
Barker, D.S., Henderson, R.W., Storey, E.: (1970) The in vivo localization of porphyrins. Br. J. Exp. Pathol. 51, 628638.Google ScholarPubMed
Becker, DM., Viljoen, J.D., Kramer, S.: (1971) The inhibition of redcelland brain ATPase by delta-aminolaevulinic acid. Biochim. Biophys. Acta 225. 2634.CrossRefGoogle ScholarPubMed
Becker, D.M., Viljoen, J.D., Kramer, S.: (1976) Porphyrin precursors and their effects in vitro on some aspects of nerve function. In: Porphyrins in human diseases (ed. Doss, M.), pp. 163172. Basel: Karger.Google Scholar
Becker, D.M., Kramer, S.: (1977) The neurological manifestations of porphyria: a review. Medicine 56. 411423.CrossRefGoogle ScholarPubMed
Berlin, N.I., Gray, C.H., Neuberger, A., Scott, J.J.: (1954) The metabolism of the porphyrin precursor, delta-aminolaevulinic acid, in normal man and in the rat. Biochem. J. 58, XXX.Google Scholar
Biempica, L., Kosower, N., Novikoff, A.: (1967) Cytochemical and ultrastructural changes in rat liver in experimental porphyria. Lab. Invest. 17, 171189.Google ScholarPubMed
Bornstein, J.C., Pickett, J.B., Diamond, I.: (1978) Inhibition of the evoked release of acetylcholine by the porphyrin precursor delta-aminolevulinic acid. Ann. Neurol. 5, 9496.Google Scholar
Busby, C.A., Dinello, R.K., Dolphin, D.: (1975) A convenient preparation of meso-tetra (4-sulfonatophenyl) porphyrin. Can. J. Chem. 53, 15541555.Google Scholar
Cavanagh, J.B., Mellick, R.A.: (1965) On the nature of the peripheral nerve lesions associated with acute intermittent porphyria. J. Neurol. Neurosurg. Psychiat. 28, 320327.CrossRefGoogle ScholarPubMed
Cavanagh, J.B., Ridley, A.R.: (1967) The nature of the neuropathy complicating acute intermittent porphyria. Lancet ii, 10231024.CrossRefGoogle Scholar
Cutler, M.G., Dick, J.M., Moore, M.K.: (1978) Effect of delta-aminolevulinic acid on frog nerve-muscle function. Life Sci. 23, 22332238.CrossRefGoogle ScholarPubMed
DE Metteis, F.: (1962) Les maladies du métabolisme des porphyrines. 2e Coll. Int. de Biologie, Saclay.Google Scholar
Denny-Brown, D., Sciarra, D.: (1945) Changes in the nervous system in acute porphyria. Brain 68, 116.Google Scholar
Dichter, H.N., Taddeini, L., Lin, S., Ayala, G.F.: (1977) Delta-aminolevulinic acid. Effect of a porphyrin precursor on an isolated neuronal preparation. Brain Res. 126, 189195.CrossRefGoogle Scholar
Dougherty, T.J., Kaufman, J.E., Goldfarb, A., Weishaupt, K.R., Boyle, D., Mittleman, A.: (1978) Photoradiation therapy for the treatment of malignant tumors. Cancer Res. 38, 26282635.Google ScholarPubMed
Feldman, D.S., Levere, R.D., Lieberman, J.S.: (1968) Presynaptic neuromuscular inhibition by delta-aminolevulinic acid, a porphyrin precursor. Trans. Am. Neurol. Assoc. 93. 206208.Google ScholarPubMed
Feldman, D.S., Levere, R.D., Lieberman, J.S., Cardinal, R.A., Watson, C.J.: (1971) Presynaptic neuromuscular inhibition of porphobilinogen and porphobilin. Proc. Natl. Acad. Sci. USA 68. 383386.CrossRefGoogle ScholarPubMed
Flügel, K.A., Druschky, K-F.: (1977) Electromyogram and nerve conduction in patients with acute intermittent porphyria. J. Neurol. 214, 267279.CrossRefGoogle ScholarPubMed
Gibson, J.B., Goldberg, A.: (1956) The neuropathology of acute porphyria. J. Pathol. Bacteriol. 71. 495509.CrossRefGoogle ScholarPubMed
Goldberg, A., Paton, W.D.M.. Thompson, J.W.: (1954) Pharmacology of the porphyrins and porphobilinogen. Br. J. Pharmacol. Chemther. 9, 9094.Google ScholarPubMed
Goldberg, A., Rimington, C: (1954) Fate of porphobilinogen in the rat. Relation to acute porphyria in man. Lancet ii. 172173.CrossRefGoogle Scholar
Granick, S., Van Den Schrieck, H.G.: (1955) Porphobilinogen and delta-aminolevulinic acid in acute porphyria. Proc. Soc. Exp. Biol. 88. 270273.CrossRefGoogle ScholarPubMed
Habermann, E.: (1977) Transmembranal and intracellular transport of pharmacologically active proteins and polypeptides. Naunyn-Schmiedeberg’s Arch. exp. Path. Pharmak. 297. 1114.CrossRefGoogle ScholarPubMed
Isaacson, L.D., Doughlas, R., Eales, L.: (1971) Inhibition of sodium and water transport by delta-aminolaevulinic acid (ALA). S. Afro. J. Lab. Clin. Med. 17, 9799.Google Scholar
Jarrett, A., Rimington, C., Willoughby, D.A.: (1956) Delta-aminolaevulinic acid and porphyria. Lancet i, 125127.CrossRefGoogle Scholar
Kaeser, H.E.: (1965) Veränderungen der Leitgeschwindigkeit bei Neuropathien und Neuritiden. Fortschr. Neurol. Psychiat. 33, 222248.Google Scholar
Karnovsky, M.J.: (1965) A formaldehyde glutaraldehyde fixative of high osmolarity for use in electron microscopy. J. Cell Biol. 27, 137A.Google Scholar
Kelly, J.F., Snell, M.E.: (1976) Hematoporphyrin derivative: a possible aid in the diagnosis and therapy of carcinoma of the bladder. J. Urol. 115, 150151.Google Scholar
Kennedy, J.C.: (1979) Hematoporphyrin photoradiation therapy: a useful alternative to ionizing radiation for the local control of cancer. Proc. Can. Assoc. Radiol. 42nd Annual Meeting, (Abstract, page 213).Google Scholar
Kosower, N.S., Rock, R.A.: (1968) Seizures in experimental porphyria. Nature (Lond) 217, 565567.CrossRefGoogle ScholarPubMed
Labbe, R.F.: (1967) Metabolic anomalies in porphyria. The result of impaired biological oxidation? Lancet i, 13611364.CrossRefGoogle Scholar
Lampert, P.W., Schochet, S.S.: (1968) Demyelination and remyelination in lead neuropathy. Electron microscopic studies. J. Neuropath. Exp. Neurol. 27. 527545.Google ScholarPubMed
Loots, J.M., Becker, D.M., Meyer, B.J., Goldstuck, N., Kramer, S.: (1975) The effect of porphyrin precursors on monosynaptic reflex activity in the isolated hemisected frog spinal cord. J. Neurol. Trans. 36. 7181.CrossRefGoogle ScholarPubMed
Marcus, R.J., Wetterberg, I., Yuwiler, A., Winters, W.D.: (1970) Electro-encephalographic and behavioral effects of experimental porphyria in the rat. Electroenceph. Clin. Neurophysiol. 29. 602607.CrossRefGoogle Scholar
Mcgillion, F.B., Moore, M.R., Goldberg, A.,: (1973) The effect of delta-aminolaevulinic acid on the spontaneous activity of mice. Scott Med. J. 18. 133.CrossRefGoogle Scholar
Meyer-Betz, F.: (1913) Untersuchungen liber die biologische (photodynamische) Wirkung des Hämatoporphyrins und anderer Derivate des Blut-und Gallenfarb-stoffs. Deutsches Arch. Klin. Med. 112. 476503.Google Scholar
Moore, M.R., Mcgillion, F.B., Goldberg, A.: (1976) Some pharmacological and behavioural effects of delta-aminolaevulinic acid. In: Porphyrins in human diseases (ed. Doss, M.), pp. 148154. Basel: Karger.Google Scholar
Müller, W.E., Snyder, S.H.: (1977) Delta-aminolevulinic acid: Influences on synaptic GABA receptor binding may explain CNS symptoms of porphyria. Ann. Neurol..’, 340342.CrossRefGoogle Scholar
Nicoll, R.A.: (1976) The interaction of porphyrin precursors with GABA receptor in the isolated frog spinal cord. Life Sci. 19, 521525.CrossRefGoogle ScholarPubMed
Niklowitz, W.J.: (1977) Subcellular mechanisms in lead toxicity: significance in childhood encephalopathy, neurological sequelae, and late dementias. In: Neurotoxicology. Vol. 1 Ed. Roizin, L.Shirakiand, H.Grcevic, N.. Raven Press, New York, pp. 289298.Google Scholar
Ryser, H.J.P.: (1970) Transport of macromolecules. especially proteins into mammalian cell. Proc. IVth Int. Congr. Pharm., Vol. 3. Schwabe, Basel, pp. 96132.Google Scholar
Sabri, M.I., Moore, C.L., Spencer, P.S.: (1979) Studies on the biochemical basis of distal axonopathies. I. Inhibition of glycolysis by neurotoxic hexacarboncompounds. J. Neurochem. 32. 683689.Google Scholar
Shanley, B.C., Taljaard, J.J.F., Deppe, W.M., Joubert, S.M.: (1972) Delta-aminolaevulinic acid in acute porphyria. S. Afr. Med. J. 46. 84.Google ScholarPubMed
Shanley, B.C., Neethling, A.C., Percy, V.A., Carstens, M.: (1975) Neurochemical aspects of porphyria. Studies on the possible neurotoxicity of delta-aminolaevulinic acid. S. Afr. Med. J. 49, 576580.Google ScholarPubMed
Shanley, B.C., Percy, V.A., Neeth-Ling, A.C: (1976) Neurochemistry of acute porphyria. Experimental studies on delta-aminolaevulinic acid and porphobilinogen. In. Porphyrins in human diseases (ed. Doss, M.), pp. 155162. Basel: Karger.Google Scholar
Sima, A.A.F., Robertson, D.M.: (1979) Peripheral neuropathy in the diabetic mutant mouse. An ultrastructural study. Lab. Invest. 40, 627632.Google ScholarPubMed
Sima, A.A.F.: (1980) Peripheral neuropathy in the spontaneously diabetic BBW-rat. An ultrastructural study. Acta Neuropath. (Berl.) 51, 223227.Google Scholar
Spencer, PS., Schaumberg, H.H.: (1976) Central-peripheral distal axonopathy – the pathology of dying-back polyneuropathies. In: Progress in Neuropathology, Volume III (ed. Zimmerman, H.M.), pp. 253295. New York and London: Grune and Stratton.Google Scholar
Spikes, J.D.: (1975) Porphyrins and related compounds as photodynamic sensitizers. Ann. NY Acad. Sci. 244, 496508.CrossRefGoogle ScholarPubMed
Tsutsui, M.Carrano, C.Tsutsui, E.A.: (1975) Tumor localizers: porphyrins and related compounds (unusual metallo-porphyrins XXIII). Ann. NY Acad. Sci. 244, 674684.CrossRefGoogle Scholar
Whetsell, W.O.J.R., Sassa, S., Bickers, D., Kappas, A.: (1978) Studies on porphyrin-heme biosynthesis in organotypic cultures of chick dorsal root ganglion. I. Observations on neuronal and non-neuronal elements. J. Neuropathol. Exp. Neurol. 37, 497507.CrossRefGoogle ScholarPubMed
Winkelman, J.: (1962) The distribution of tetraphenylporphinesulfonate in the tumor-bearing rat. Cancer Res. 22, 589596.Google ScholarPubMed
Winkelman, J.: (1967) Metabolic studies on the accumulation of tetraphenylporphinesulfonate in tumors. Experienta 23, 949950.CrossRefGoogle Scholar
Winkelman, J., Hayes, J.E.: (1963) Distribution of endogenous and parenterally administered porphyrin in viable and necrotic portions of a transplantable tumor. Nature 200. 903904.Google Scholar
Winkelman, J., Slater, G., Grossman, J.: (1967) The concentration in tumor and other tissues of parenterally administered tritium- and 14C-labeled tetraphenylporphinesulfonate. Cancer Res. 27, 20602064.Google Scholar
Wochnik-Dyjas, D., Niewiadomska, M., Kostrzewska, E.: (1978) Porphyric polyneuropathy and its pathogenesis in the light of electrophysiological investigations. J. Neurol. Sci. 35. 243256.CrossRefGoogle ScholarPubMed