Marzo A, Corsico N, Cardace G, Morabito E
Department of Drug Metabolism and Pharmacokinetics, Sigma-Tau S.p.A., Pomezia, Rome, Italy.
Arzneimittelforschung. 1993 Mar;43(3):339-42.
The effect of diabetes induced by streptozotocin and that of acetyl-L-carnitine (ALC) hydrochloride (CAS 5080-50-2) treatment on the homeostasis of the levocarnitine (L-carnitine) moiety was investigated in Sprague-Dawley rats. The diabetic status was ascertained by measuring blood glucose. L-carnitine (LC), total acid soluble L-carnitine (TC) and ALC were measured in serum, tissues and urine by radioenzymatic methods. Short-chain L-carnitine esters (SCLCE) were obtained by subtracting LC from TC. Serum concentration of L-carnitine moiety was decreased in diabetic when compared to normal rats; whereas ALC oral treatment (50 and 150 mg/kg p.o. for 4 weeks) in diabetic rats increased, dose-dependently, all the components of L-carnitine moiety, SCLCE and ALC being completely restored. In the liver of diabetic rats all the analytes proved to be higher than in normal rats, mainly LC and TC. A similar trend was observed in skeletal muscle, at least with LC and TC, whereas SCLCE and ALC were not affected. The treatment with ALC increased the liver concentration of all the analytes in a dose-related way whereas in skeletal muscle only LC and TC showed an increase with the highest dose of ALC. Myocardium and kidneys showed a decrease of all the analytes in diabetes; the treatment with ALC normalized the situation in kidneys, in a dose-related way, but not in the myocardium. Urinary excretion and renal clearance of L-carnitine moiety increased in diabetes; an additional dose-related increase was observed with the ALC treatment.
在斯普拉格-道利大鼠中研究了链脲佐菌素诱导的糖尿病以及盐酸乙酰左旋肉碱（ALC，CAS 5080-50-2）治疗对左旋肉碱部分内环境稳态的影响。通过测量血糖来确定糖尿病状态。采用放射酶法测定血清、组织和尿液中的左旋肉碱（LC）、总酸溶性左旋肉碱（TC）和ALC。短链左旋肉碱酯（SCLCE）通过从TC中减去LC获得。与正常大鼠相比，糖尿病大鼠血清中左旋肉碱部分的浓度降低；而糖尿病大鼠口服ALC治疗（50和150 mg/kg，口服，持续4周）剂量依赖性地增加了左旋肉碱部分的所有成分，SCLCE和ALC完全恢复。在糖尿病大鼠的肝脏中，所有分析物均高于正常大鼠，主要是LC和TC。在骨骼肌中也观察到类似趋势，至少LC和TC是这样，而SCLCE和ALC未受影响。ALC治疗以剂量相关的方式增加了肝脏中所有分析物的浓度，而在骨骼肌中，只有LC和TC在ALC最高剂量时显示增加。糖尿病时心肌和肾脏中所有分析物均减少；ALC治疗使肾脏情况剂量依赖性地恢复正常，但对心肌无效。糖尿病时左旋肉碱部分的尿排泄和肾清除率增加；ALC治疗观察到额外的剂量相关增加。
