Neurochemical aspects of porphyria. Studies on the possible neurotoxicity of delta aminolaevulinic acid

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dc.contributor.authorShanley, B. C.
dc.contributor.authorNeethling, A. C.
dc.contributor.authorPercy, V. A.
dc.contributor.authorCarstens, M.
dc.date.accessioned2011-03-18T14:57:55Z
dc.date.available2011-03-18T14:57:55Z
dc.date.issued1975
dc.descriptionArticle
dc.descriptionThe original publication is available at http://www.samj.org.za
dc.description.abstractIt has been proposed that delta aminolaevulinic acid (ALA), which is overproduced in the inherited hepatic porphyrias, may be responsible for the neurological manifestations of the acute attacks seen in these disorders. Studies were conducted in rats to test the neurotoxicity of ALA. It was found that, after intraperitoneal or subcutaneous injections, ALA is rapidly eliminated via the kidneys. In nephrectomised animals sustained elevation of blood ALA concentration was demonstrated, but despite this, brain uptake was extremely low. Experiments on incorporation of [4 14C] ALA into brain haem yielded similar information. After intraventricular injection of [4 14C] ALA, significant uptake by brain tissue occurred. The subsequent disappearance of ALA was moderately rapid and was virtually complete within 24 hours. Uptake of [4 14C] ALA was apparently significantly greater in the hypothalamus than in other brain areas. The subcellular distribution of radioactivity did not reveal any preferential uptake by nerve endings. Intraventricular injection of unlabelled ALA revealed definite but transitory neurotoxic effects in doses of 3 micromoles and greater. These include involuntary movements and ataxia. No effect of ALA administration on brain protein synthesis could be demonstrated. It is concluded that ALA does have effects on the nervous system in vivo, but the significance of these effects in relation to the pathogenesis of the neurological manifestations of acute porphyria is questionable.en-ZA
dc.description.sponsorshipSouth African Medical Research Council
dc.description.sponsorshipDr A. J. van Wyk
dc.description.sponsorshipUniversity of Stellenbosch
dc.description.sponsorshipCape Provincial Administration
dc.description.versionPublishers' version
dc.format.extentp. 576-580
dc.identifier.citationShanley, B.C., Neethling, A.C., Percy, V.A & Carstens, M. 1975, Neurochemical aspects of porphyria. Studies on the possible neurotoxicity of delta aminolaevulinic acid, SA Medical Journal, 49(14), 576-580, http://archive.samj.org.za/
dc.identifier.issn0256-9574 (print)
dc.identifier.issn2078-5135 (online)
dc.identifier.urihttp://hdl.handle.net/10019.1/7741
dc.language.isoen_ZA
dc.publisherHealth and Medical Publishing Group (HMPG)
dc.rights.holderHealth and Medical Publishing Group (HMPG)
dc.subjectHepatotoxicologyen_ZA
dc.subjectRats as laboratory animalsen_ZA
dc.subjectHepatic porphyrias -- Diagnosisen_ZA
dc.subjectDelta-aminolaevullinic aciden_ZA
dc.subjectPorphyrias -- Neurological aspectsen_ZA
dc.subjectRats -- Effect of intraventricular injections onen_ZA
dc.subjectNeurotoxicity in ratsen_ZA
dc.titleNeurochemical aspects of porphyria. Studies on the possible neurotoxicity of delta aminolaevulinic aciden_ZA
dc.typeArticle
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