title: Carnosine ameliorates liver fibrosis and hyperammonemia in cirrhotic rats.
abstract: OBJECTIVE
  Chronic liver injury and cirrhosis leads to liver failure. Hyperammonemia is a deleterious consequence of liver failure. On the other hand, oxidative stress seems to play a pivotal role in the pathogenesis of liver fibrosis as well as in the cytotoxic mechanism of ammonia. There is no promising therapeutic agent against ammonia-induced complications. The present study was conducted to evaluate the role of carnosine (CA) administration on liver pathological changes, elevated plasma ammonia, and its consequent events in cirrhotic rats.
  
  
  METHODS
  Bile duct ligated (BDL) rats were used as a model of cirrhosis. CA (250, 500, and 1000mg/kg, daily, i.p) was administered for 28 consecutive days to BDL animals. At the end of treatments, markers of oxidative stress and liver fibrosis was determined in liver and serum biomarkers of liver injury and plasma ammonia was assessed. Moreover, changes in animals' locomotor activity were monitored.
  
  
  RESULTS
  Severe bridging fibrosis, inflammation, and necrosis in liver, along with elevated serum biomarkers of liver injury were evident in BDL animals. Furthermore, plasma ammonia was drastically elevated in cirrhotic rats and animals' locomotor activity was suppressed. It was found that CA (250, 500, and 1000mg/kg, daily, i.p) significantly alleviated liver injury and its consequent events in cirrhotic rats. The data suggested that CA is not only a useful and safe agent to preserve liver function, but also prevented hyperammonemia and brain damage as a deleterious consequence of cirrhosis and liver failure.
authors.affiliation: Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, P.O. Box 1583, 71345 Roknabad, Karafarin Street, Shiraz, Fars, 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, P.O. Box 1583, 71345 Roknabad, Karafarin Street, Shiraz, Fars, Iran. Electronic address: rezaheidari@hotmail.com.
authors.forename: Reza
authors.initials: R
authors.lastname: Heidari
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: Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, P.O. Box 1583, 71345 Roknabad, Karafarin Street, Shiraz, Fars, Iran.
authors.forename: Mohammed Mehdi
authors.initials: MM
authors.lastname: Ommati
authors.affiliation: Iran Food and Drug Administration (IFDA), 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: Somayeh
authors.initials: S
authors.lastname: Mousavi
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: 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: Mahdi
authors.initials: M
authors.lastname: Zarei
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: Mojgan
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: 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: Arastoo
authors.initials: A
authors.lastname: Saeedi
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
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
mesh_terms: D000818:Animals; D002336:Carnosine / Q000627:therapeutic use*; D022124:Hyperammonemia / Q000150:complications / Q000188:drug therapy*; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002336:Carnosine