The Potential Neuroprotective Role of Citicoline in Hepatic Encephalopathy

Omid Farshad,1 Pedram Keshavarz,2 Reza Heidari,1 Mina Farahmandnejad,1,3 Sara Azhdari,4 Akram Jamshidzadeh1,3 1Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; 2Department of Radiology, Tbilisi State Medical University (TSMU), Tbilisi, Georgia; 3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; 4Department of Anatomy and Embryology, School of Medicine, Bam University of Medical Sciences, Bam, IranCorrespondence: Reza Heidari; Akram JamshidzadehPharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, IranEmail rheidari@sums.ac.ir; ajamshid@sums.ac.irPurpose: Hepatic encephalopathy (HE) is described as impaired brain function induced by liver failure. Ammonia is the most suspected chemical involved in brain injury during HE. Although the precise mechanism of HE is not clear, several studies mentioned the role of oxidative stress in ammonia neurotoxicity. In animal models, the use of some compounds with antioxidant properties was reported to reduce the neurotoxic effects of ammonia, improve energy metabolism, and ameliorate the HE symptoms. Citicoline is a principal intermediate in the biosynthesis pathway of phosphatidylcholine that acts as neurovascular protection and repair effects. Various studies mentioned the neuroprotective and antioxidative effects of citicoline in the central nervous system. This study aims to investigate the potential protective effects of citicoline therapeutic in an animal model of HE.Materials and Methods: Mice received acetaminophen (APAP,1g/kg, i. p.) and then treated with citicoline (500 mg/kg, i.p) one and two hours after APAP. Animals were monitored for locomotor activity and blood and brain ammonia levels. Moreover, markers of oxidative stress were assessed in the brain tissue.Results: The result of the study revealed that plasma and brain ammonia and the liver injury markers increased, and locomotor activity impaired in the APAP-treated animals. Besides, an increase in markers of oxidative stress was evident in the brain of the APAP-treated mice. It was found that citicoline supplementation enhanced the animal’s locomotor activity and improved brain tissue markers of oxidative stress.Conclusion: These data propose citicoline as a potential protective agent in HE. The effects of citicoline on oxidative stress markers could play a fundamental role in its neuroprotective properties during HE.Keywords: antioxidants, citicoline, hepatic encephalopathy, hyperammonemia, oxidative stress