| dc.description.abstract | Axonal abnormalities induced by exposure to the n-hexane metabolites 2,5-hexanedione (2,5-HD) or 2,5-hexanediol (2,5-Hdol) were studied in rats by immunohistochemical techniques using monoclonal antibodies against neuro-filament proteins. These techniques produced more distinct and reproducible results than the traditional silver technique. It could thus be shown that the swollen axons contained increased amounts of neurofilaments but not of tubulin. In most of the major organs exposed to 2,5-HD or 2,5-HDol swollen axons were observed. The exposed rats showed motor impairment, mainly paralysis. Testicular and retinal degeneration were also seen. In contrast to the retinal effects, the testicular changes and the paralysis disappeared after ending the exposure. Immediately after the exposure to 2,5-HD or 2,5-Hdol, the retina had a loss of photoreceptor cells that progressed during the post-exposure periods. The cones were more resistant than the rods to the n-hexane metabolites and light exposure. A greater survival of photoreceptors at the ora serrata in exposed albino rats suggested that the 2,5-HD or 2,5-HDol effects require light in order to cause cellular damage. Swollen axons were found in the iris of exposed rats, which might be consistent with an observed impairment of pupil function, and thus an increased retinal light exposure and possibly enhanced photoreceptor loss. Albino rats exposed to 2,5-HDol in total darkness had no loss of photoreceptors. Electroretinography confirmed the morphological observations of damage to, and loss of, photoreceptor cells in the presence of light from fluorescent tubes when exposed to 2,5-HD or 2,5-HDol. This toxic effect on the retina progressed during the post-exposure periods. 2,5-HD penetrates the blood-aqueous humor/retina barrier. The concentration of 2,5-HD in the aqueous humor was considerably higher than in serum. This indicated an active transport from blood to aqueous humor. Twenty-four hours after the exposure no 2,5-HD could be found, demonstrating that there is no long-term accumulation of 2,5-HD. Rhodopsin may play a key role in the destruction of the photoreceptors. It is suggested that during exposure to n-hexane metabolites, the all trans-retinal is replaced by 2,5-HD. A subsequent reaction between 2,5-HD and light energy would then lead to the formation toxic pyrrol substances. The toxic products may either directly damage the retinal cells, or do so via a further interaction with light. | eng |
| dc.description.abstract | Exponering för n-hexanmetaboliterna, 2,5-hexandion (2,5-HD) och 2,5-hexandiol (2,5-HDol) medförde svällda axoner i flera av råttans olika organ. Även testikel och retinaskador påvisades. Märkning med monoklonala antikroppar mot neurofilamentprotein och tubulin visade att de svällda axonerna innehåller ökad mängd neurofilament men ej tubulin. Immunperoxidastekniken ger en snabb, precis visualisering av axonerna och dessas eventuella skador. Förlamning och testikelskador gick tillbaka efter avslutad exponering för n-hexanmetaboliterna. Fotoreceptorskadorna förvärrades emellertid även efter avslutad exponering. Kvarvarande fotoreceptorer vid Ora Serrata visar att 2,5-HD och 2,5-HDol är beroende av ljusenergi för sin skadande effekt på näthinnan. Tapparna, som utgör 2-3 % av fotoreceptorerna, tycks mer resistenta mot exponering för n-hexanmetaboliter och ljus än stavarna. Ingen retinal skada vid exponering för 2,5-HD kunde påvisas morfologiskt hos albinoråttor i totalt mörker. Däremot kunde man konstatera att 2,5-HD potentierar ljusinducerad morfologisk skada, som fortsätter efter upphörande av exponeringen för n-hexanmetaboliterna. En elektrofysiologisk ögonundersökning bekräftade de morfologiska resultaten. 2,5-HD penetrerade blod-ögonkammar/näthinnebarriärerna. 2,5-HD koncentreras därvid i ögonkammarvätskan, sannolikt mot en koncentrations-gradient. Ingen ackumulation av 2,5-HD under långtidsexponering som kunde förklara den fortsatta förlusten av fotoreceptorer efter avslutad exponering kunde påvisas. De uppkomna toxiska skadorna var dosrelaterade. | swe |
