2,5-Hexanedione concentrations and morphological changes within the eye of albino rat.
Exposure to 2,5-hexanedione (2,5-HD), a major n-hexane metabolite, can cause loss of photoreceptor cells, particularly when combined with light energy. The aims of this study were to document the levels of 2,5-HD reached in relation to time in retina, aqueous humor, and serum of the Sprague-Dawley albino rat after: (1) a single oral administration of 2,5-HD (0.04 g/ kg body wt.) by tube feeding; and (2) after subchronic oral administration of 2,5-HD. In addition, morphometric analysis of the retina was carried out to evaluate cell loss at the end of administration and after various periods of recovery. The 2,5-HD concentration in retinal tissue, aqueous humor, and serum reached a peak within 1 h after exposure to a single dose of 2,5-HD. Twenty four hours after the exposure, only a minor amount of 2,5-HD could be detected in the retina and aqueous humor. When 2,5-HD was administered subchronically (0.04 g/kg body wt. per day, for 35 days) no loss of photoreceptor cells was seen immediately after the end of exposure or at the end of a 4-week recovery period. Rats exposed to 0.60 g/kg body wt. per day for 11 days showed no significant loss of photoreceptor cells immediately after the end of exposure but there was a substantial loss of photoreceptor cells after 2 and 4 weeks of recovery. The results demonstrate that 2,5-HD reaches the aqueous humor and retina, and penetrates blood-aqueous humor/retina barriers after oral administration. Moreover, retinal degeneration seen in the animals may be directly caused by 2,5-HD and these changes are dose dependent.
Bäckström
B
B
Department for Work and Health, National Institute for Working Life, Solna, Sweden.
Shibata
E
E
Nylén
P
P
Collins
V P
VP
D000284:Administration, Oral; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D005123:Eye / Q000187:drug effects* / Q000378:metabolism*; D006588:Hexanones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D009498:Neurotoxins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D006588:Hexanones; D009498:Neurotoxins; C011269:2,5-hexanedione