β-Hydroxybutyrate의 Flurothyl-유발 발작 감수성에 대한 효과
Effect of β-Hydroxybutyrate on Flurothyl-Induced Seizure Susceptibility
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목 적:케톤생성식이요법은 유용한 항간질치료법으로 널리 인정 받으면서 임상에서 활발히 사용되고 있지만 그 항간질 작용기전에 대해서는 아직까지 거의 알려져 있는 바가 없다. 이에 본 연구에서는 케톤생성식이요법에 의해 인체 내에서 생성되는 케톤체 중 하나인 BHB가 직접적인 항경련효과를가 나타낼 수 있는지 알아보고자 flurothyl-유발 발작 동물 모델을 이용하여 조사하였다. 방 법:Sprague-Dawley 백서 34마리를 실험에 사용하였는데, 이들을 각각 17마리씩 치료군과 대조군의 2군으로 나누었다. 치료군의 동물들에게는 BHB를 20 mmol/kg 용량으로 복강내 주사하였고 대조군에게는 같은 양의 생리식염수를 주사하였다. BHB 주사 후 15분이 경과한 시점에, flurhythyl-유발 발작 감수성 검사를 시행하고 그 결과를 비교하였다. 결 과:BHB 치료군 동물의 발작 잠복기가 대조군보다 유의하게(P<0.05) 더 긴 것을 관찰하였으며, 이로써 BHB가 그 자체로 flurothyl-유발 발작 감수성을 직접적으로 낮춘다는 사실을 확인할 수 있었다. 결 론:본 연구의 결과는 flurothyl-유발 발작 동물모델에서 케톤체인 BHB가 그 자체로 직접적인 항경련효과가 있음을 시사하므로, 현재까지도 거의 알려진 바가 없는 케톤생성식이요법의 항간질기전을 연구하는 데에 장차 중요한 디딤돌의 하나가 될 수 있을 것으로 기대된다.
Abstract
Purpose:The ketogenic diet (KD) remains a therapy in search of explanation although it is an established treatment for patients with intractable seizures. It was designed to mimic the biochemical changes seen upon fasting, specifically the formation of ketone bodies: acetoacetate (ACA), β-hydroxybutyrate (BHB), and to a lesser extent, acetone. The present study was designed to investigate the protective effect of BHB on flurothyl-induced seizures in rats. Methods:Thirty-four male Sprague-Dawley rats were divided into two equal groups. Experimental rats (n=17) were injected intraperitoneally with BHB (20 mmol /kg), while control animals (n=17) with normal saline. Fifteen minutes later, seizures were chemically induced by flurothyl infusion (40 mL/min). Seizure susceptibility was defined as the latency from the start of flurothyl infusion to the onset of a generalized seizure. Shorter latencies reflected greater seizure susceptibility. Results:The mean (±SEM) latency to the onset of a generalized seizure in the experimental animals treated with BHB was 476.5±13.9 seconds, which was significantly longer (P<0.05) than the control (438.0±10.5 seconds). Conclusion:This study demonstrated the significant decrease in flurothyl-induced seizure susceptibility in rats treated with BHB. Our results suggest that BHB may be directly anticonvulsant.
참고문헌 (16)
- Wilder RM, "The effects of ketonemia on the course of epilepsy", Mayo Clin Proc, 2, pp.307~308 (1921)
- Nordli DR Jr, "The ketogenic diet revisited: back to the future", Epilpepsia, 38, pp.743~749 (1997)
- Freeman JM, "The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children", Pediatrics, 102, pp.1358~1363 (1998)
- Kossoff EH, "Efficacy of the Atkins diet as therapy for intractable epilepsy", Neurology, 61, pp.1789~1791 (2003)
- Schwartz RM, "Metabolic effects of three ketogenic diets in the treatment of severe epilepsy", Dev Med Child Neurol, 31, pp.152~160 (1989)
- Bough KJ, "Higher ketogenic diet ratios confer protection from seizures without neurotoxicity", Epilepsy Res, 38, pp.15~25 (2000)
- Greene AE, "Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies", J Neurochem, 86, pp.529~537 (2003)
- Gilbert DL, "The ketogenic diet: seizure control correlates better with serum beta-hydroxybutyrate than with urine ketones", J Child Neurol, 15, pp.787~790 (2000)
- Bough KJ, "Anticonvulsant mechanisms of the ketogenic diet", Epilepsia, 48, pp.43~58 (2007)
- Bough KJ, "Seizure resistance is dependent upon age and calorie restriction in rats fed a ketogenic diet", Epilepsy Res, 35, pp.21~28 (1999)
- Rho JM, "Acetoacetate, acetone, and dibenzylamine (a contaminant in l-(+)-beta-hydroxybutyrate) exhibit direct anticonvulsant actions in vivo", Epilepsia, 43, pp.358~361 (2002)
- Kim DW, "Effect of the Ketogenic Diet on Flurothyl-Induced Seizure Susceptibility", Journal of Korean Epilepsy Society, 5, pp.119~123 (2001)
- DeVivo DC, "How to use other drugs (steroids) and the ketogenic diet" (1983), Raven Press
- Duan W, "Brain-derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice", J Neurochem, pp.76619~76626 (2001)
- Kim DW, "The ketogenic diet is anticonvulsant against flurothyl-induced seizures in mature mice", Epilepsia, 39(Suppl 6), pp.46~ (1998)
- Rho JM, "Age-dependent differences in flurothyl seizure sensitivity in mice treated with a ketogenic diet", Epilepsy Res, 37, pp.233~240 (1999)