The Potential Neuroprotective Role of Citicoline in Hepatic Encephalopathy

Abstract

Purpose

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

Abbreviations

HE, hepatic encephalopathy; APAP, acetyl-para-aminophenol; acetaminophen; GSH, glutathione; ROS, reactive oxygen species.

Acknowledgments

The authors gratefully acknowledge the Pharmaceutical Sciences Research Center and the Vice-Chancellor of Research Affairs of Shiraz University of Medical Sciences for providing technical and financial (Grant 98-01-36-19776) support of the current investigation.

Disclosure

The authors declare no conflicts of interest in this work.