| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
Carnitine (beta-hydroxy-gamma-N-trimethylaminobutyrate) is widely distributed among tissues and has been well established as an essential cofactor for the transport of long-chain acyl CoA through the inner mitochondrial membrane in extraneural tissues. In the brain, however, while carnitine is present, synthesized, and taken up after systemic administration, its physiological roles remain unknown. In our previous studies, we found that carnitine was effective clinically as well as biochemically in suppressing neurotoxicities of ammonia (see Igisu et al. J.Occup. Health 37 : 75-82,1995). In the present study, we examined effects of carnitine inseizures induced by pentylenetetrazol (PTZ), one of the most widely used epileptogenic agents. When ddY mice were pretreated with L-carnitine (5,10 and 20 mmol/kg), clonic as well as tonic seizures induced by PTZ were dose-dependently suppressed. Time-respones study (PTZ was injected 1,5,15 and 30 min after L-carnitine) showed that the anticonvulsive effects were apparent when the interval between L-carnitine and PTZ administration was 15-30 min. Saline containing 43% sucrose prolonged the latency to the first clonic seizure but less effective than 20 mmol/kg L-carnitine and did not suppress clonic or tonic seizures. Alterations in brain energy metabolites caused by PTZ including increase of lactate and decrease of ATP and phosphocreatine were also suppressed by L-carnitine. L-Carnitine was more potent than D-carnitine in prolonging the latency to the first clonic seizure and in decreasing the frequency of clonic as well as tonic seizures. The anticonvulsive effects of L-carnitine in PTZ-induced seizures may be unrelated to the transport of longchain acyl CoA since they were not interfered with by D-carnitine.
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