Pierno Sabata, Tricarico Domenico, Liantonio Antonella, Mele Antonietta, Digennaro Claudio, Rolland Jean-François, Bianco Gianpatrizio, Villanova Luciano, Merendino Alessandro, Camerino Giulia Maria, De Luca Annamaria, Desaphy Jean-François, Camerino Diana Conte
Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari "Aldo Moro", Via Orabona 4-campus, 70125, Bari, Italy,
Age (Dordr). 2014 Feb;36(1):73-88. doi: 10.1007/s11357-013-9544-9. Epub 2013 May 30.
Age-related skeletal muscle decline is characterized by the modification of sarcolemma ion channels important to sustain fiber excitability and to prevent metabolic dysfunction. Also, calcium homeostasis and contractile function are impaired. In the aim to understand whether these modifications are related to oxidative damage and can be reverted by antioxidant treatment, we examined the effects of in vivo treatment with an waste water polyphenolic mixture (LACHI MIX HT) supplied by LACHIFARMA S.r.l. Italy containing hydroxytirosol (HT), gallic acid, and homovanillic acid on the skeletal muscles of 27-month-old rats. After 6-week treatment, we found an improvement of chloride ClC-1 channel conductance, pivotal for membrane electrical stability, and of ATP-dependent potassium channel activity, important in coupling excitability with fiber metabolism. Both of them were analyzed using electrophysiological techniques. The treatment also restored the resting cytosolic calcium concentration, the sarcoplasmic reticulum calcium release, and the mechanical threshold for contraction, an index of excitation-contraction coupling mechanism. Muscle weight and blood creatine kinase levels were preserved in LACHI MIX HT-treated aged rats. The antioxidant activity of LACHI MIX HT was confirmed by the reduction of malondialdehyde levels in the brain of the LACHI MIX HT-treated aged rats. In comparison, the administration of purified HT was less effective on all the parameters studied. Although muscle function was not completely recovered, the present study provides evidence of the beneficial effects of LACHI MIX HT, a natural compound, to ameliorate skeletal muscle functional decline due to aging-associated oxidative stress.
与年龄相关的骨骼肌衰退的特征是肌膜离子通道发生改变,这些通道对于维持纤维兴奋性和预防代谢功能障碍至关重要。此外,钙稳态和收缩功能也会受损。为了了解这些改变是否与氧化损伤有关以及是否可以通过抗氧化治疗恢复,我们研究了由意大利LACHIFARMA S.r.l.提供的含有羟基酪醇(HT)、没食子酸和高香草酸的废水多酚混合物(LACHI MIX HT)对27月龄大鼠骨骼肌的体内治疗效果。经过6周的治疗,我们发现对于膜电稳定性至关重要的氯离子ClC-1通道电导以及在将兴奋性与纤维代谢偶联中起重要作用的ATP依赖性钾通道活性均有所改善。两者均使用电生理技术进行分析。该治疗还恢复了静息胞质钙浓度、肌浆网钙释放以及收缩的机械阈值,后者是兴奋-收缩偶联机制的一个指标。在接受LACHI MIX HT治疗的老年大鼠中,肌肉重量和血液肌酸激酶水平得以维持。LACHI MIX HT处理的老年大鼠大脑中丙二醛水平的降低证实了其抗氧化活性。相比之下,纯化的HT给药对所有研究参数的效果较差。尽管肌肉功能没有完全恢复,但本研究提供了证据,证明天然化合物LACHI MIX HT对改善因衰老相关氧化应激导致的骨骼肌功能衰退具有有益作用。