Martin Sherry Joseph, Baskaran Udhaya Lavinya, Vedi Mahima, Sabina Evan Prince
School of Biosciences and Technology, VIT University , Vellore, Tamil Nadu , India.
Toxicol Mech Methods. 2014 Dec;24(8):584-92. doi: 10.3109/15376516.2014.956910. Epub 2014 Sep 10.
Therapy using Isoniazid (INH) and Rifampicin (RIF) leads to induction of hepatotoxicity in some individuals undergoing anti-tuberculosis treatment. In this study, we assessed the effect of Spirulina fusiformis on INH and RIF induced hepatotoxicity in rats compared with hepatoprotective drug Silymarin. Induction of hepatotoxicity was measured by changes in the liver marker enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase). The antioxidant status was also analyzed in liver tissue homogenate and plasma by measurement of superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, and lipid peroxidation levels. We also aimed to study the binding and interactions of the transcription factors Pregnane X Receptor (PXR) and Farnesoid X Receptor (FXR) with INH, RIF, and representative active compounds of Spirulina fusiformis by in silico methods. The administration of INH and RIF resulted in significant (p < 0.05) decrease in the antioxidant levels and total protein levels. There was also a significant (p < 0.05) increase in the levels of liver marker enzymes. Spirulina fusiformis was seen to protect the parameters from significant changes upon challenge with INH and RIF in a dose-dependent manner. This was corroborated by histological examination of the liver. The results of the in silico analyses further support the wet lab results.
使用异烟肼(INH)和利福平(RIF)进行治疗会导致一些接受抗结核治疗的个体出现肝毒性。在本研究中,我们评估了与保肝药物水飞蓟宾相比,钝顶螺旋藻对INH和RIF诱导的大鼠肝毒性的影响。通过肝脏标志物酶(天冬氨酸转氨酶、丙氨酸转氨酶和碱性磷酸酶)的变化来测定肝毒性的诱导情况。还通过测量超氧化物歧化酶、过氧化氢酶、谷胱甘肽 - S - 转移酶、谷胱甘肽还原酶和脂质过氧化水平,对肝组织匀浆和血浆中的抗氧化状态进行了分析。我们还旨在通过计算机模拟方法研究转录因子孕烷X受体(PXR)和法尼酯X受体(FXR)与INH、RIF以及钝顶螺旋藻的代表性活性化合物的结合和相互作用。给予INH和RIF导致抗氧化水平和总蛋白水平显著(p < 0.05)降低。肝脏标志物酶水平也显著(p < 0.05)升高。钝顶螺旋藻在受到INH和RIF攻击时,能以剂量依赖的方式保护各项参数不发生显著变化。肝脏的组织学检查证实了这一点。计算机模拟分析的结果进一步支持了湿实验室结果。