Febuxostat mitigates concanavalin A-induced acute liver injury via modulation of MCP-1, IL-1ß, TNF-α, neutrophil infiltration, and apoptosis in mice.

AIM: Liver plays a crucial role in innate immunity reactions. This role predisposes the liver to innate-mediated liver injury when uncontrolled inflammation occurs. In this study, the effect of febuxostat administration on acute liver injury induced by concanavalin A (Con A) injection into mouse eye orbital sinus was studied. MATERIALS AND METHODS: Two doses of febuxostat (10 and 20 mg/kg, orally) were administered either 1 h before or 30 min after the administration of Con A. Febuxostat at a low dose (10 mg/kg) before and after Con A modulated the elevation of serum ALT, liver uric acid, liver myeloperoxidase (MPO), and interleukin-1ß (IL-1ß) induced by Con A. The same dose of febuxostat before Con A also decreased serum total bilirubin and neutrophil infiltration, as evidenced by flow cytometry and histopathological analysis. KEY FINDINGS: Febuxostat at a high dose (20 mg/kg) significantly improved serum ALT, AST, albumin, total bilirubin, liver uric acid, MPO, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), IL-1ß, and neutrophil infiltration induced by Con A administration. The results of histopathological examination of liver cells paralleled the observed biochemical improvements. Hepatocyte apoptosis as evidenced by immunohistochemical examination of cleaved caspase-3 was markedly decreased in the febuxostat protection and treatment groups, in a dose-dependent manner SIGNIFICANCE: These results indicate that febuxostat, especially at the higher dose, may be an effective inhibitor of immune reactions evoked by Con A administration.

Effects of Concanavalin A, fed as a constituent of Jack bean (Canavalia ensiformis L.) seeds, on the humoral immune response and performance of broiler chickens.

An experiment was conducted to investigate the effects of the lectin, Concanavalin A (Con A), contained in raw Jack bean (JB) (Canavalia ensiformis, L.) seeds on the immunological response of broilers. A maize-soybean meal basal diet was prepared to which either 2.5, 5, or 10% of ground raw Jack bean (RJB) seeds was added. The RJB seeds contained 24 g Con A/kg on a dry matter basis, as measured by rocket immunoelectrophoresis. Similar diets were prepared by using the same levels of JB after toasting at 190 C for 16 min. In addition, the basal diet was pair-fed to groups of chicks at the level of feed intake of chicks fed the 10% RJB diet. Each diet was fed to six groups of six chicks for 6 wk. At 5 wk, 15 of chicks from each diet were immunized against Brucella abortus (BA) and the anti-BA antibody titers were determined 1 wk later by ELISA. Antibody production against Con A was also measured by the same method. Binding of Con A to intestinal villi and subsequent endocytosis were confirmed by microscopic examination using a specific peroxidase-antiperoxidase-staining technique. Performance was recorded weekly. Feed intake and weight gain were reduced (P < 0.05) only by the diet containing 10% RJB, indicating that broiler chicks can tolerate daily intakes of 100 mg of Con A over 6 wk without affecting growth. Toasted JB diets supported adequate chick performance. The antibody response to BA did not differ with dietary treatment. Serum from chicks fed raw JB also contained antibodies against Con A. The bursa of Fabricius, thymus, spleen, and pancreas dry weights, as a percentage of dry body weight, were not affected by the experimental diets. The data indicated that Con A binds to the cells of the gastrointestinal tract, passes into the general circulation and, eventually, elicits an immunological response without affecting the production of antibodies to BA.