Effect of phosphatidylserine on cirrhosis-induced hepatic encephalopathy: Response to acute endotoxemia in cirrhotic rats
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Golnaz Zamanian,1,* Seyed Mohammad Tavangar,2 Parto Mirzaei,3 Ahmad Reza Dehpour,4 Farahnaz Jazaeri,5
1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2. Tehran University of Medical Sciences, Tehran, Iran
3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
4. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Introduction: In cirrhosis, the levels of proinflammatory cytokines are high in the liver and blood. Endotoxin decreases level of consciousness in cirrhotic rats. Phosphatidylserine exists in the cell membrane structure and is essential for the survival of neurons. Phosphatidylserine receptor is found in phagocytic cells and also activates the signaling of membrane proteins in apoptotic process. Therefore this study was aimed to explore the hypothesis that hepatic encephalopathy is prevented by phosphatidylserine treatment and if so, whether this is associated with altered level of proinflammatory cytokines in the brain.
- Methods: Cirrhosis was induced by surgical ligation of the bile duct in male Wister rats. The groups were treated with phosphatidylserine and saline for 4 weeks. Brain IL6, TNFα and the expression of phosphatidylserine receptor were assessed. Intraperitoneal injections of either saline or lipopolysaccharide (0.1 mg/kg) were administered to each group. Finally, animal behavior, blood ammonia and the expression of toll like receptor 4 were examined in the brain.
- Results: Cirrhosis in rats was associated with altered expression of toll-like receptor4 in brain cortex and phosphatidylserine treatment increases toll-like receptor4 receptor expression. Phosphatidylserine had anti-inflammatory effect in healthy rats but no effect in cirrhotic rats. Chronic phosphatidylserine treatment decreased blood ammonia in BDL cirrhotic rats treated with lipopolysaccharide.
- Conclusion: The brain of cirrhotic rat is more susceptible to acute endotoxemia and chronic phosphatidylserine treatment decreases blood ammonia and encephalopathy in cirrhotic rats by encountering endotoxin. Phosphatidylserine may boost immune system against endotoxin.
- Keywords: Biliary cirrhosis, Hepatic encephalopathy, Acute endotoxemia, Phosphatidylserine
