Previous attempts to demonstrate abnormalities in lipid peroxidation in various forms of the neuronal ceroid-lipofuscinoses (NCL) have been unrewarding up to and including the peroxide level (peroxidase). In this experiment a survey was made in a canine model of NCL to study the relative concentration of 4-hydroxynonenal (HNE), a fragment derived from an acute oxidation product of unsaturated fatty acids. Peripheral blood cells and various tissues from an affected and a normal control dog were surveyed. HNE was assayed after reacting with O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine to form the 4-hydroxynonenal (O-pentafluorobenzyl) oxime. This reaction product was then separated by capillary gas liquid chromatography (g/c) and quantitated by flame ionization. The survey showed that neutrophils isolated from affected dogs and carriers contained abnormal amounts of HNE when compared with normal control animals. Two carriers had mean values of +3,289% above normal, and neutrophils from two affected animals were +4,873% above normal. In addition, an examination of the relative HNE levels in brain, retina, retinal pigment epithelium (RPE), and kidney of an affected dog compared with a control animal also showed abnormal levels of HNE, particularly in brain (+168%) and in the RPE (+135%), the two organs exhibiting the most severe pathologic damage unique to these disorders. These findings, although preliminary, clearly document a role for HNE in this canine form of human NCLs. The well-known cytotoxic properties of HNE and other alpha,beta unsaturated aldehydes suggest a primary role in the pathogenetic events of this disorder.
|Original language||English (US)|
|Number of pages||11|
|Journal||American journal of medical genetics. Supplement|
|State||Published - 1988|