Taurine treatment preserves brain and liver mitochondrial function in a rat model of fulminant hepatic failure and hyperammonemia Akram Jamshidzadeh a,b , Reza Heidari a, *, Mozhgan Abasvali c , Mehdi Zarei b , Mohammad Mehdi Ommati d , Narges Abdoli e , Forouzan Khodaei b , Yasaman Yeganeh b , Faezeh Jafari b , Azita Zarei b , Zahra Latifpour b , Elnaz Mardani b , Negar Azarpira f , Behnam Asadi b , Asma Najibi b a Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran b Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran c Students Research Committee, Shiraz University of Medical Sciences, International Branch, Shiraz, Iran d Department of Animal Science, School of Agriculture, Shiraz University, Iran e Food and Drug Organization, Ministry of Health, Tehran, Iran f Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran A R T I C L E I N F O Article history: Received 11 June 2016 Received in revised form 20 November 2016 Accepted 21 November 2016 Keywords: Amino acid Ammonia Bioenergetics Brain injury Hepatic encephalopathy Oxidative stress A B S T R A C T 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 (400 mg/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 1000 mg/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. © 2016 Elsevier Masson SAS. All rights reserved. 1. Introduction Hepatic encephalopathy (HE) is a deleterious clinical compli- cation accompanied by acute and chronic liver injury [1]. Although the exact cause of HE is not known, there is agreement on the predominant role of ammonia in HE etiology [2]. Ammonia is metabolized by the liver to the urea in healthy subjects. Damaged livers are unable to metabolize ammonia. Hence, this toxic chemical is elevated in the systemic circulation and, eventually, damages the brain. Ammonia is a neurotoxin that mostly influences astrocytes in the central nervous system (CNS) [3,4]. It also has several direct toxic effects on neurons [4]. Ammonia causes brain edema, oxidative stress, and inflammation when its level rises in HE [5]. Consequently, a decline in brain function occur in patients with HE [5]. Hyperammonemia also affects hepatocytes and liver function [6]. Disturbed mitochondrial function and oxidative stress are implicated in ammonia-induced cytotoxicity [3,7]. It has been reported that brain energy metabolism is interrupted in chronic * Corresponding author at: P.O. Box 1583, 71345, Roknabad, Karafarin St., Shiraz, Fars, Iran. E-mail address: rezaheidari@hotmail.com (R. Heidari). http://dx.doi.org/10.1016/j.biopha.2016.11.095 0753-3322/© 2016 Elsevier Masson SAS. All rights reserved. Biomedicine & Pharmacotherapy 86 (2017) 514–520 Available online at ScienceDirect www.sciencedirect.com