title: Taurine treatment preserves brain and liver mitochondrial function in a rat model of fulminant hepatic failure and hyperammonemia.
abstract: 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.
authors.affiliation: 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.
authors.forename: Akram
authors.initials: A
authors.lastname: Jamshidzadeh
authors.affiliation: Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: rezaheidari@hotmail.com.
authors.forename: Reza
authors.initials: R
authors.lastname: Heidari
authors.affiliation: Students Research Committee, Shiraz University of Medical Sciences, International Branch, Shiraz, Iran.
authors.forename: Mozhgan
authors.initials: M
authors.lastname: Abasvali
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Zarei
authors.affiliation: Department of Animal Science, School of Agriculture, Shiraz University, Iran.
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Ommati
authors.affiliation: Food and Drug Organization, Ministry of Health, Tehran, Iran.
authors.forename: Narges
authors.initials: N
authors.lastname: Abdoli
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Forouzan
authors.initials: F
authors.lastname: Khodaei
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Yeganeh
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Faezeh
authors.initials: F
authors.lastname: Jafari
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Azita
authors.initials: A
authors.lastname: Zarei
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Latifpour
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Elnaz
authors.initials: E
authors.lastname: Mardani
authors.affiliation: Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Negar
authors.initials: N
authors.lastname: Azarpira
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Behnam
authors.initials: B
authors.lastname: Asadi
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Asma
authors.initials: A
authors.lastname: Najibi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000641:Ammonia / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000188:drug therapy / Q000378:metabolism; D022124:Hyperammonemia / Q000188:drug therapy* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D017114:Liver Failure, Acute / Q000188:drug therapy* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013654:Taurine / Q000494:pharmacology*; D013853:Thioacetamide / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D013853:Thioacetamide; D013654:Taurine; D000641:Ammonia; D000255:Adenosine Triphosphate
keywords: Amino acid; Ammonia; Bioenergetics; Brain injury; Hepatic encephalopathy; Oxidative stress