Abstract

Scope Lactoferrin (Lf) possess a protective potential to liver, but whether it can prevent alcoholic liver injury (ALI) remains unclear. Methods and Results Four groups of male C57BL/6J mice are fed with different diets, namely, AIN-93G diet for control (CON) and ethanol (EtOH) groups, and AIN-93G diet with 0.4% and 4% casein replaced by Lf for low-dose Lf (LLf) and high-dose Lf (HLf) groups, respectively. ALI is induced by giving 20% ethanol ad libitum combined with four “binges”. Lf can remarkably decrease EtOH-induced mortality. Lf promotes aldehyde dehydrogenase-2 (ALDH2) expression and suppressing cytochrome P450 2E1 (CYP2E1) overexpression, resulting in the reduced hepatic superoxide and inflammation levels, which ultimately leads to the hepatic injury alleviation. However, HLf increases acetyl-CoA carboxylase and fatty acid synthase protein levels, which suggests that excessive intake may weaken the beneficial effects of Lf. Moreover, LLf increases the relative abundances of Akkermansia and Lactobacillus . Additionally, the study shows that Lf likely exerts action in its digestive product forms rather than intact Lf molecular in normal condition. Conclusion LLf can ameliorate ALI, which is associated with the regulation of hepatic alcohol metabolism and the modulation of gut microbiota. However, excessive Lf intake may result in a diminished benefit.