부산대학교 도서관

Chronic liver diseases are characterized by persisting parenchymal injury that can result in chronic activation of inflammatory and wound healing response. Cerium oxide nanoparticles (CeO2NPs) have proven to behave as free radical scavengers and/or anti-inflammatory agents. The aim of the first study was to determine whether CeO2NPs display hepatoprotective properties in experimental chronic liver disease. Most CeO2NPs were located in the liver and it reduced hepatic steatosis, ameliorated systemic inflammatory biomarkers and improved portal pressure without affecting mean arterial pressure. In addition, a marked reduction in mRNA expression of inflammatory cytokines, ET-1 and messengers related to oxidative or endoplasmic reticulum stress signaling pathways was observed in the liver of rats receiving CeO2NPs. This was associated with reduced macrophage infiltration and reduced abundance of caspase-3, a-SMA and inflammatory cytokines. In conclusion, CeO2NPs administration to CCl4-treated rats protects against chronic liver injury by reducing liver steatosis and portal hypertension and markedly attenuating the intensity of the inflammatory response, thereby suggesting that CeO2NPs may be of therapeutic value in chronic liver disease. Patients and rats with advanced cirrhosis have portal hypertension and circulatory dysfunction. Synthetic arginine vasopressin (AVP) receptor agonists able to induce systemic and mesenteric vasoconstriction have shown their usefulness in reducing portal pressure (PP) in this condition. In the second study, we assessed the potential therapeutic value of a new V1a-AVP receptor partial agonist with a preferential splanchnic vasoconstrictor effect (FE-204038) in rats with cirrhosis and ascites. The hemodynamic effects of cumulative intravenous doses of FE-204038, terlipressin, or vehicle were investigated. FE-204038 dose-dependently decreased PP, did not modify mean arterial pressure, and increased SVR. The effect of the V1a-AVP receptor partial agonist on PP was associated with an improvement in urine volume and urinary excretion of sodium during the first day of treatment. SVR was higher and cardiac output and ascites volume were lower in rats with cirrhosis and ascites treated with FE-204038. V1a-AVP receptor expression in rats with cirrhosis and ascites was markedly enhanced in the mesenteric circulation compared to the thoracic aorta. Conclusion: FE-204038 increases sodium excretion and reduces portal hypertension and ascites in experimental cirrhosis. V1a-AVP receptor partial agonism could be a useful pharmacological treatment in decompensated patients with cirrhosis.