|Budget Amount *help
¥2,700,000 (Direct Cost : ¥2,700,000)
Fiscal Year 1998 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1997 : ¥1,900,000 (Direct Cost : ¥1,900,000)
|Keywords||Neurotoxicity / Diabetes mellitus / 2,5-Hexanedione / Motor nerve conduction velocity / Glucose / Sorbitol / Fructose / Myo-inositol / Neurotoxicity, / Diabetes mellitus, / 2,5-Hexanedione, / Motor nerve conduction velocity, / Glucose, / Sorbitol, / Fructose, / ラット / 2,5-HD / 透析プローブ / 灌流液 / Microdialysis / 血清中濃度 / AUC / Pharmacokinetics|
The mechanism of synergistic effect by non-neurotoxic substances on 2,5-hexandinone induced neurotoxicity' has been finished according to the original study plan. 2,5-bexandinone along or combined with methyl ethyl ketone, acetone, or toluene were subcutaneously injected to groups of rat. Concentrations 2,5-hexandinone in serum, bile, urine, feces, liver, lunge, kidney, brain and sciatic nerve were measured, and according to the concentrations determined, the 2,5-hexandinone pharmacokinetics were calculated. In the same time, activities of the cytochrome p450 enzymes in the liver and lung were also detected. Based on these results, the pharmacokinetics of 2,5-hexanedione can be influenced by combined injections of methyl ethyl ketone, acetone, and toluene indicated by the decreases of 2,5-hexandinone clearance in the co-treated groups. Results from these pharmacokinetics changes, the concentrations of 2,5-hexandinone in brain and nerve were increased, and these increases can be supposed to play a key role for the synergistic effect of methyl ethyl ketone and acetone on the neurotoxicity induced by 2, 5-hexandinone. Furthermore, the clearance decreases in the co-treated groups is supposed result. from the inhibition of the cytochrome p450 enzymes activity in the liver. Parts of the results in the present study have been published in the Journal of Occupational Health, International Achieves of Occupational and Environmental Health, and Neurochemical Research.