Hayashi Y, Muranaka Y, Kirimoto T, Asaka N, Miyake H, Matsuura N
Pharmacology Research Laboratory, Taiho Pharmaceutical Co.. Ltd., Tokushima, Japan.
Biol Pharm Bull. 2000 Jun;23(6):770-3. doi: 10.1248/bpb.23.770.
MET-88, 3-(2,2,2-trimethylhydrazinium) propionate, suppresses carnitine synthesis by inhibiting (gamma-butyrobetaine hydroxylase. The purpose of this study was to clarify the effects of suppression of carnitine synthesis on carnitine and lipid contents in tissues. MET-88 (50, 100, 200 or 400 mg/kg/d) was administered orally to male SD rats for 10, 30 or 60 d. Total carnitine and lipid (triglycerides, non-esterified fatty acids) contents were measured in heart and liver. In both tissues, treatment with MET-88 dose-dependently decreased total carnitine levels, and the reduction reached the plateau state after 30 d at each dose. MET-88 had no effect on lipid content in the heart, but increased the lipid content in the liver at the highest doses. Treatment with MET-88 at 400 mg/kg for 60 d resulted in no pathologic findings in the histological study, and also had no effect on parameters of liver function such as glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase as judged from the results of blood biochemical analysis. We concluded that long-term treatment with MET-88 decreased the carnitine content to a constant level in both heart and liver, but had no effect on lipid contents in the heart, although it affected lipid metabolism in the liver.
MET - 88，即3 -（2,2,2 - 三甲基肼基）丙酸酯，通过抑制γ-丁基甜菜碱羟化酶来抑制肉碱合成。本研究的目的是阐明抑制肉碱合成对组织中肉碱和脂质含量的影响。将MET - 88（50、100、200或400毫克/千克/天）口服给予雄性SD大鼠10、30或60天。测量心脏和肝脏中的总肉碱和脂质（甘油三酯、非酯化脂肪酸）含量。在这两种组织中，MET - 88处理均剂量依赖性地降低了总肉碱水平，并且在每个剂量下30天后降低达到平台期。MET - 88对心脏中的脂质含量没有影响，但在最高剂量时增加了肝脏中的脂质含量。在组织学研究中，以400毫克/千克的剂量用MET - 88处理60天未发现病理变化，并且从血液生化分析结果判断，对肝功能参数如谷草转氨酶和谷丙转氨酶也没有影响。我们得出结论，长期用MET - 88处理会使心脏和肝脏中的肉碱含量降低至恒定水平，但对心脏中的脂质含量没有影响，尽管它影响了肝脏中的脂质代谢。
