Dynamic change of hepatocyte during PXR-induced liver enlargement / 药学学报

Pregnane X receptor (PXR), a member of nuclear receptor superfamily, plays an important role in xenobiotic and endogenous metabolism, endocrine balance, and cell proliferation, etc. Previous study has shown that pregnenolone 16α-carbonitrile (PCN), a mouse PXR agonist, could induce liver enlargement. And we found that the change in hepatocytes exhibits regional distribution characteristics: hepatocyte enlargement occurs around the central vein (CV) area, while hepatocyte proliferation occurs around the portal vein (PV) area. In this study, the dynamic changes of hepatocytes during PXR-induced liver enlargement were determined. Serum and liver samples from male C57BL/6 mice were collected for biochemical and pathological analysis after PCN treatment for 1, 2, 3, 5 days, respectively. The animal experiment was approved by the Animal Ethics Committee of Sun Yat-Sen University. The results showed that with the increase in the PCN treatment days, the feature of this regional change of hepatocyte around the CV and PV areas became more and more obvious. At the same time, the factors related to hepatocyte enlargement, such as the expression of PXR downstream genes and the hepatic content of triglyceride (TG), has gradually increased. The upregulation of proliferation-related proteins and downregulation of cyclin-dependent kinases inhibitor proteins were observed in the early stage of PCN treatment, suggesting that hepatocyte proliferation occurs earlier than hepatocyte enlargement during PXR-induced liver enlargement. This study reveals the dynamic change of hepatocytes during PXR-induced liver enlargement and provides a new insight in liver enlargement promoted via PXR activation.

Lipidomics analysis on schisandrol B-induced liver enlargement in mice / 药学学报

Schisandrol B (SolB) is one of the active constituents from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. Our previous studies found that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. We further found that SolB significantly induces liver enlargement but the mechanisms remain unclear. The purpose of this study was to investigate the change of lipidome in liver tissues during SolB-induced hepatomegaly. The animal experiment protocol was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. Serum and liver samples of male C57BL/6 mice were collected after intraperitoneal injection of SolB (100 mg·kg-1·d-1) for 5 days. Lipidomics analysis was performed using Q Exactive UHPLC-MS/MS system. The results showed that SolB significantly promoted liver enlargement in mice without liver injury and inflammation. Lipid accumulation was observed in the liver tissues after SolB treatment. Thirty-five lipids were identified with significant change and triglycerides (TG) were found to have the most significant increase in SolB-treated group, indicating the increase of energy production during SolB-induced hepatomegaly. This study reveals the impact of SolB on lipid metabolism and provides a potential explanation for liver enlargement induced by SolB.

The enlargements of liver size induced by orotic acid and di (2-ethyl hexyl) phthalate occur in different metabolic pathways.

The present study was conducted to elucidate the metabolic pathways by which enlarged liver size of patients undergoing disorders of orotic acid de novo metabolism and those patients of enlarged liver size induced by di(2-ethyl hexyl) phthalate in rats as animal model. The results showed that rats-treated with orotic acid generated liver triglyceride content 400% higher than that of the control accompanied with a significant decrease of phospholipid levels (P<0.05). The rates of lipogenic enzymes, both fatty acid synthase (FAS) and phosphatidate phosphohydrolase (PAP), increase accompanying promotions of liver triglyceride content without any changes in fatty acid degradation pathway. However, those rats-treated with di(2- ethyl hexyl) phthalate generated liver phospholipid level significantly higher than of the control accompanied with a markedly decreased the liver triglyceride levels. Both FAS and PAP activities were almost similar with those controls but the rates of fatty acid degradation were increased approximately by 2.5-fold of control. In conclusion: The enlargement of liver size induced by orotic acid is associated with largely retains triglyceride molecules in liver tissues, whereas those induced by di(2-ethyl hexyl) is associated with the induction of phosphorylation generating an increase of liver phospholipid levels.

A Case of Acute Lymphoblastic Leukemia Accompanied with Lactic Acidosis and Kidney Enlargement

There have been several reported cases of acute lymphoblastic leukemia with severe lactic acidosis in adults. In these cases, kidney and liver enlargement that was caused by leukemic infiltration frequently accompanied the acute lymphoblastic leukemia and severe lactic acidosis. Chemotherapy is the only treatment that can rapidly correct the lactic acidosis and normalize the liver and kidney enlargement. We report here on a case of acute lymphoblastic leukemia that was accompanied with severe lactic acidosis and kidney enlargement.

Gauchers disease in early infancy

The first case of Gauchers disease observed in the Philippines is reported in an infant of 10 monthsThe disease is characterized by storage of kerasin in the cells of the reticulo-endothelial apparatus resulting in marked splenomegaly and liver enlargementThe different types of lipoid storage diseases, diagnosis and treatment of Gauchers disease are discussed. (Summary)