Search

Abstract: Mast cells are involved in various liver diseases and appear to play a broader pathogenic role than originally thought. They may participate in the splanchnic alterations related to a porto-systemic shunt. To verify this hypothesis we studied the serum and hepatic histological changes in rats four weeks after an end-to-side portacaval shunt. In this experimental model of chronic liver insufficiency we also assessed the mucosal mast cells (MMC) and connective tissue mast cells (CTMC) in the liver, mesenteric lymph nodes and small intestine, as well as the serum levels of rat mast cell protease-II (RMCP-II). The results show liver and testes atrophy, with hypoalbuminemia (p =0.0001), hyperbilirubinemia (p =0.0001) and increase in aspartate aminotransferase (p =0.004) and alanine aminotransferase (p =0.0001). Hepatic histopathology demonstrates hepatocytic necrosis and apoptosis, portal inflammation, biliary proliferation, steatosis and fibrosis. There is a decrease of MMCs and CTMCs in the liver, while in the ileum CTMCs increase and MMCs decrease. These results suggest the involvement of mast cells in the pathophysiological splanchnic impairments in this experimental model. In particular, the decreased number of liver mast cells may be associated with the hepatic atrophy. If this is the case, we propose that the disruption of the hepato-intestinal axis after a portocaval shunt in the rat could inhibit the ability of the liver to developing an appropriate repair response mediated by mast cells. [Copyright &y& Elsevier]

Abstract: Patients with liver malfunction often suffer from hepatic encephalopathy, a neurological complication which can affect attention and cognition. Diverse experimental models have been used to study brain alterations that may be responsible for hepatic encephalopathy symptoms. The aim of the study was to determine whether cognitive impairment found in cirrhosis could be due to disturbance of acetylcholinesterase activity. Acetylcholinesterase activity was assessed in the brains of Wistar rats with thioacetamide-induced cirrhosis. The cirrhotic group displayed up-regulation of acetylcholinesterase levels in the entorrhinal cortex, anterodorsal and anteroventral thalamus and accumbens, whereas down-regulation was found in the CA1, CA3 and dentate gyrus of the hippocampus. Our results indicate that the experimental model of hepatic encephalopathy by chronic administration of thioacetamide presents alterations of acetylcholinesterase activity in brain limbic system regions, which play a role in attention and memory. [Copyright &y& Elsevier]

Summary: It is currently believed that portal hypertension induces an inflammatory response in which mast cells may be involved. The aim of this study was to verify the involvement of the intestinal submucosal and mesenteric lymph node mast cells in the splanchnic inflammatory response related to portal hypertension. Mast cell infiltration in the intestine (duodenum, jejunum, ileum, caecum and distal colon) and in the mesenteric lymph node complex (MLC) was measured using a stereological method in sham-operated rats (SO; n=12), in two experimental models of portal hypertension, chronic (triple partial portal vein ligation, TPVL; n=12) and transient (microsurgical partial hepatectomy; n=12) and in rats in which the MLC was resected (n=12). The small and large bowel submucosal infiltration increases in MLC-resected rats (p=0.0001), in TPVL rats (p=0.0001) and in rats with partial hepatectomy (p=0.0001). An extensive mast cell infiltration in the MLC (p=0.0001) was found in TPVL rats and in rats with partial hepatectomy (347.40±45.25 and 351.92±99.28/mm3, respectively) in relation to sham-operated rats (135.27±30.28/mm3). We conclude that mast cells could be involved in the splanchnic alterations developed in the surgical experimental models of portal hypertension studied. [Copyright &y& Elsevier]