The Role of Brain Mitochondria in Hepatic Encephalopathy: Potential Therapeutic Targets
محل انتشار: پانزدهمین همایش سراسری سم شناسی ایران
سال انتشار: 1398
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 423
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شناسه ملی سند علمی:
TOXICOLOGY15_037
تاریخ نمایه سازی: 15 بهمن 1398
چکیده مقاله:
Introduction: Hepatic encephalopathy (HE) is a critical CNS complication ensued liver failure. HE is associated with increased free radical formation, tissue inflammation, disturbed neurotransmission, astrocytes swelling, brain edema, and brain herniation. Ammonia, involved in HE, is a neurotoxin which induces a wide range of CNS functional disturbances. Ammonia-induced oxidative stress, mitochondrial dysfunction, and energy crisis are known as the major mechanisms of brain injury in HE. Hyperammonemia also affects the liver and hepatocytes. In view of the severe CNS complications ensued HE, potential therapeutic points of intervention need to be investigated. A role for CNS mitochondrial damage and energy crisis has been considered in HE. It has been found that ammonia induces collapse of mitochondrial membrane potential, induced mitochondrial swelling, and increased reactive oxygen. Hence, ammonia-induced mitochondrial injury and compromised brain energy metabolism might play a vital role in the pathogenesis of ammonia neurotoxicity. Therefore, targeting mitochondria seems to be a therapeutic point of intervention in the treatment of HE. This study focuses on the concept that mitochondrial dysfunction and cellular energy crisis indeed plays a critical role in the pathogenesis of hyperammonemia-induced brain injury. Further, we will highlight the potential therapeutic value of mitochondrial protecting agents and energy providers in the management of HE. The data collected in this study might provide clues to new therapeutic interventions aimed at minimizing HE-associated complications.
نویسندگان
R Heidari
Pharmacutical Sciences Research Center
A Jamshidzadeh
Pharmacutical Sciences Research Center- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Hadi Niknahad
Pharmacutical Sciences Research Center- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran