Severe Acute Hepatic Dysfunction Induced by Ammonium Acetate Treatment Results in Choroid Plexus Swelling and Ventricle Enlargement in the Brain.

Hepatic encephalopathy is a major cause of liver failure. However, the pathophysiological role of ventricle enlargement in brain edema remains unclear. Here, we used an acute hepatic encephalopathy mouse model to examine the sequential pathological changes in the brain associated with this condition. We collected tissue samples from experimental animals treated with ammonium acetate at 3 and 24 h post-injection. Despite the normalization of the animal's ammonia levels, samples taken at 24 h after injection exhibited distinct enlargement of lateral ventricles. The choroid plexus samples obtained at 3 h post-ammonium acetate treatment indicated enlargement; however, this swelling was reduced at the later timepoint. The aquaporin-1 proteins that regulate the choroid plexus were localized both in the apical membrane and the cytoplasm of the epithelia in the control; however, they translocated to the apical membranes of the epithelia in response to ammonia treatment. Therefore, severe acute hepatic encephalopathy induced by ammonium acetate administration caused enlargement of the ventricles, through swelling of the choroid plexus and aquaporin-1 transport and aggregation within the apical membranes.

Protective Efficacy of the Ingestion of Mandarin Orange Containing ß-Cryptoxanthin on Lipopolysaccharide-induced Acute Nephritis.

ß-cryptoxanthin is a common carotenoid pigment found in fruit, especially in Satsuma mandarins and in persimmons. After ingestion, ß-cryptoxanthin is distributed to and accumulates in organs, such as the liver, lung, and kidney. Recent studies have reported that because of its antioxidant defense, ß-cryptoxanthin performs several important functions in the preservation of human health and in the prevention of several diseases, including cancer and osteoporosis. The present study aims to determine whether ß-cryptoxanthin has a protective effect on renal glomeruli during acute nephritis. To develop our acute nephritis mouse model, we induced kidney inflammation in mice using lipopolysaccharide. To analyze pathological changes in the renal glomeruli of these mice, tissue sections of the kidney were analyzed by hematoxylin-eosin and periodic acid-Schiff staining. In mice with acute nephritis, we observed a thickening of the basal membrane in the renal glomeruli. By ultrastructural analysis, abnormalities in the foot cells were also identified. In the ß-cryptoxanthin-ingested mice, these pathological changes were decreased. Migration of urinal proteins occurred in mice with acute nephritis, but this was decreased in ß-cryptoxanthin-ingested mice, such that it correlated with the blood concentration of ß-cryptoxanthin. Furthermore, in ß-cryptoxanthin-ingested mice, both the accumulation and activation of inflammatory cells were decreased in the renal glomeruli. These results suggest that ß-cryptoxanthin ingestion may produce great improvement in acute nephritis. These findings provide new insights into ß-cryptoxanthin and its protective effect, and provide a new target for pharmacological therapy in human disease.

[Pathological changes in hepatocytes of mice with obesity-induced type 2 diabetes by monosodium glutamate].

Type 2 diabetes caused by chronic obesity is a major lifestyle-related disease. The present study aimed to determine the pathological changes in hepatocytes in chronic obesity. To develop our type 2 diabetes mouse model, we induced chronic obesity to mice by monosodium glutamate. By overeating, the mice significantly increased their body weight compared with age-matched healthy animals. To analyze the pathological changes in hepatocytes of chronic obesity before preclinical stage of type 2 diabetes, the mice were analyzed by hematoxylin-eosin staining of tissue sections at 15 w of age. In these mice, we observed eosin-negative accumulations of hepatocytes around central veins in the hepatic lobule. By Oil-Red O staining, the eosin-negative granules were identified in the lipid droplets. We then ascertained whether these lipid droplets of hepatocytes in the obese mice could be modified by diet. After 24 h of diet restriction, the lipid droplets of hepatocytes in the obese mice were swollen. Furthermore, after 48 h of the diet restriction, the lipid droplets continued swelling and the autophagy-like structures that were found in the healthy mice under the same condition in the obese mice were not observed. These results suggest that the obese mice might have delayed energy metabolism, which might have influenced the mechanisms of hepatocytes. These findings provide new insight into the functional changes in chronic obesity-induced type 2 diabetes and it is possible that the pathological feature make a contribution to promise the target of pharmacological therapy.