Effects of Long-Term Mildronate Treatment on Cardiac and Liver Functions in Rats
Effects of Long-Term Mildronate Treatment on Cardiac and Liver Functions in Rats
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DOI：
10.1111/j.1742-7843.2009.00461.x
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发表时间：
2009-12-01
影响因子：
3.1
通讯作者：
Dambrova, Maija
中科院分区：
文献类型：
--
作者：
Liepinsh, Edgars;Kuka, Janis;Dambrova, Maija
米屈酸钠是一种心脏保护药物，通过降低机体组织中左旋肉碱浓度和调节心肌能量代谢来改善缺血心功能。本研究的目的是描述大鼠长期米屈膦酸钠治疗后的心血管功能和肝脏状况。此外，还监测了大鼠血浆脂质谱的变化，以及米屈酸盐、左旋肉碱和γ -丁甜菜碱在大鼠组织中的浓度变化。Wistar大鼠每天口服100、200或400 mg/kg剂量的米屈酸钠，持续4、8或12周。米屈酸钠降低左旋肉碱的作用呈剂量依赖性。然而，在大约四周的治疗后，肉碱水平达到了一个平稳期。在另外几周的治疗中，肉毒碱水平没有明显变化。所获得的结果提供了证据，即使是高剂量的米膦酸钠也不会改变离体大鼠心脏的心血管参数和功能。此外，肝组织冷冻的组织学评价和肝毒性生化指标的测定表明，所有测量值都在正常参考范围内。我们的研究结果证明，长期服用米膦酸钠会引起肉碱稳态的显著变化，但它与心脏损伤或肝功能紊乱无关。
Mildronate is a cardioprotective drug that improves cardiac function during ischaemia and functions by lowering l-carnitine concentration in body tissues and modulating myocardial energy metabolism. The aim of the present study was to characterise cardiovascular function and liver condition after long-term mildronate treatment in rats. In addition, changes in the plasma lipid profile, along with changes in the concentration of mildronate, l-carnitine and gamma-butyrobetaine were monitored in the rat tissues. Wistar rats were perorally treated daily with a mildronate dose of either 100, 200 or 400 mg/kg for 4, 8 or 12 weeks. The l-carnitine-lowering effect of mildronate was dose-dependent. However, the carnitine levels reached a plateau after about four weeks of treatment. During the additional weeks of treatment, the carnitine levels were not considerably changed. The obtained results provide evidence that even a high dose of mildronate does not alter cardiovascular parameters and the function of isolated rat hearts. Furthermore, the histological evaluation of liver tissue cryosections and measurement of biochemical markers of hepatic toxicity showed that all the measured values were within the normal reference range. Our results provide evidence that long-term mildronate administration induces significant changes in carnitine homeostasis, but it is not associated with cardiac impairment or disturbances in liver function.