Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Biomed Pharmacother. 2017 Feb;86:514-520. doi: 10.1016/j.biopha.2016.11.095. Epub 2016 Dec 23.
Ammonia-induced mitochondrial dysfunction and energy crisis is known as a critical consequence of hepatic encephalopathy (HE). Hence, mitochondria are potential targets of therapy in HE. The current investigation was designed to evaluate the role of taurine treatment on the brain and liver mitochondrial function in a rat model of hepatic encephalopathy and hyperammonemia. The animals received thioacetamide (400mg/kg, i.p, for three consecutive days at 24-h intervals) as a model of acute liver failure and hyperammonemia. Several biochemical parameters were investigated in the serum, while the animals' cognitive function and locomotor activity were monitored. Mitochondria was isolated from the rats' brain and liver and several indices were assessed in isolated mitochondria. Liver failure led to cognitive dysfunction and impairment in locomotor activity in the rats. Plasma and brain ammonia was high and serum markers of liver injury were drastically elevated in the thioacetamide-treated group. An assessment of brain and liver mitochondrial function in the thioacetamide-treated animals revealed an inhibition of succinate dehydrogenase activity (SDA), collapsed mitochondrial membrane potential, mitochondrial swelling, and increased reactive oxygen species (ROS). Furthermore, a significant decrease in mitochondrial ATP was detected in the brain and liver mitochondria isolated from thioacetamide-treated animals. Taurine treatment (250, 500, and 1000mg/kg) decreased mitochondrial swelling, ROS, and LPO. Moreover, the administration of this amino acid restored brain and liver mitochondrial ATP. These data suggest taurine to be a potential protective agent with therapeutic capability against hepatic encephalopathy and hyperammonemia-induced mitochondrial dysfunction and energy crisis.
氨诱导的线粒体功能障碍和能量危机是肝性脑病（HE）的一个关键后果。因此，线粒体是治疗 HE 的潜在靶点。本研究旨在评估牛磺酸治疗在肝性脑病和高血氨大鼠模型中对大脑和肝脏线粒体功能的作用。动物接受硫代乙酰胺（400mg/kg，i.p.，连续 3 天，间隔 24 小时）作为急性肝衰竭和高血氨的模型。研究了血清中的几种生化参数，同时监测了动物的认知功能和运动活动。从大鼠的大脑和肝脏中分离出线粒体，并评估了分离线粒体的几种指标。肝衰竭导致大鼠认知功能障碍和运动活动受损。血浆和大脑中的氨含量升高，硫代乙酰胺治疗组的血清肝损伤标志物明显升高。对硫代乙酰胺处理动物的大脑和肝脏线粒体功能的评估表明，琥珀酸脱氢酶活性（SDA）受到抑制，线粒体膜电位崩溃，线粒体肿胀，活性氧（ROS）增加。此外，还检测到从硫代乙酰胺处理动物分离的脑和肝线粒体中线粒体 ATP 显著减少。牛磺酸治疗（250、500 和 1000mg/kg）可减少线粒体肿胀、ROS 和 LPO。此外，给予这种氨基酸可恢复脑和肝线粒体 ATP。这些数据表明牛磺酸是一种潜在的保护剂，具有治疗肝性脑病和高血氨诱导的线粒体功能障碍和能量危机的能力。
