Yogeeta Surinder Kumar, Gnanapragasam Arunachalam, Senthilkumar Subramanian, Subhashini Rajakannu, Devaki Thiruvengadam
Department of Biochemistry, University of Madras, Guindy Campus, Chennai-600 025, Tamilnadu, India.
Life Sci. 2006 Dec 23;80(3):258-63. doi: 10.1016/j.lfs.2006.09.012. Epub 2006 Sep 22.
Altered membrane integrity has been suggested as a major factor in the development of cellular injury during myocardial necrosis. The present study was designed to investigate the effect of the combination of ferulic acid (FA) and ascorbic acid (AA) on lysosomal hydrolases and membrane-bound phosphatases during isoproterenol (ISO) induced myocardial necrosis in rats. Induction of rats with 1SO (150 mg/kg b.wt, i.p.) for 2 days resulted in a significant increase in the activities of lysosomal hydrolases (beta-D-glucuronidase, beta-D-galactosidase, beta-D-N-acetylglucosaminidase, acid phosphatase and cathepsin-D) in the heart and serum. A significant increase in plasma lactate level, cardiac levels of sodium, calcium and a decrease in cardiac level of potassium was also observed, which was paralleled by abnormal activities of membrane-bound phosphatases (Na(+)-K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase) in the heart of ISO-administered rats. Pre-co-treatment with the combination of FA (20 mg/kg b.wt) and AA (80 mg/kg b.wt) orally for 6 days significantly attenuated these abnormalities and restored the levels to near normalcy when compared to individual drug treated groups. The combination of FA and AA preserved the membrane integrity by mitigating the oxidative stress and associated cellular damage more effectively when compared to individual treatment groups. In our study, the protection conferred by FA and AA might be through the nitric oxide pathway and by their ability of quenching free radicals. In conclusion, these findings indicate the synergistic modulation of lysosomal hydrolases and membrane phosphatases by the combination of FA and AA.
膜完整性改变被认为是心肌坏死时细胞损伤发生的一个主要因素。本研究旨在探讨阿魏酸（FA）和抗坏血酸（AA）联合应用对异丙肾上腺素（ISO）诱导的大鼠心肌坏死过程中溶酶体水解酶和膜结合磷酸酶的影响。用ISO（150mg/kg体重，腹腔注射）诱导大鼠2天，导致心脏和血清中溶酶体水解酶（β-D-葡萄糖醛酸酶、β-D-半乳糖苷酶、β-D-N-乙酰氨基葡萄糖苷酶、酸性磷酸酶和组织蛋白酶-D）的活性显著增加。还观察到血浆乳酸水平显著升高、心脏钠和钙水平升高以及心脏钾水平降低，同时给予ISO的大鼠心脏中膜结合磷酸酶（Na(+)-K(+)ATP酶、Ca(2+)ATP酶和Mg(2+)ATP酶）的活性异常。与单独用药治疗组相比，预先口服FA（20mg/kg体重）和AA（80mg/kg体重）联合用药6天可显著减轻这些异常，并使各项指标恢复到接近正常水平。与单独治疗组相比，FA和AA联合应用通过更有效地减轻氧化应激和相关细胞损伤来维持膜完整性。在我们的研究中，FA和AA提供的保护作用可能是通过一氧化氮途径以及它们清除自由基的能力实现的。总之，这些发现表明FA和AA联合应用对溶酶体水解酶和膜磷酸酶具有协同调节作用。
