Akika Fukawa*, Orie Kobayashi, Makoto Yamaguchi and Akira Hosono
Objective: Alpha-lactalbumin (αLA) accounts for about 20% of whey protein, which shown to have anti-inflammatory effects, but its effects on acute hepatitis have not been reported. We investigated the hepatoprotective effects of αLA in an acute hepatitis model. Since the effects of αLA on macrophages, which are related to inflammation, have not been clarified, we conducted DNA microarrays to investigate the anti-inflammatory mechanism of αLA. Methods: Sprague-Dawley rats were divided into three groups; control diet-fed group (Normal), D-galactosamine (GalN) and lipopolysaccharide (LPS)-treated and control diet-fed group (GalN/LPS), and GalN/LPS-treated, αLA- containing diet-fed group (GalN/LPS+αLA). One week after starting the test diet, rats were injected with GalN/LPS and the parameters in blood and liver were evaluated. Anti-inflammatory effect of αLA on RAW 264.7 macrophages were investigated by DNA microarray. Results: An αLA-containing diet inhibited the elevation of plasma alanine aminotransferase, aspartate aminotransferase, hepatic interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) after the administration of GalN/LPS compared with the control diet. In RAW 264.7 cells, αLA reduced the increase of LPS-induced IL-6 and TNF-α. When the DNA microarray analysis of αLA-treated, and non-αLA-treated groups were compared, it revealed 84 genes were differentially expressed. Gene ontology analysis identified "response to LPS" and "regulation of leukocyte differentiation" as the enriched terms. Conclusion: The present study indicates that an αLA-containing diet suppresses GalN/LPS-induced hepatitis via an anti-inflammatory effect through the reduction of pro-inflammatory cytokines. It is suggested that the response of hepatic macrophages to LPS and the differentiation patterns of macrophages might be the underlying mechanism.
Published Date: 2021-07-05; Received Date: 2021-06-14