Lactoferrin Prevents Chronic Alcoholic Injury by Regulating Redox Balance and Lipid Metabolism in Female C57BL/6J Mice

Abstract

This study aimed to investigate the preventive effects of lactoferrin (Lf) on chronic alcoholic liver injury (ALI) in female mice. Female C57BL/6J mice were randomly divided into four groups: control group (CON), ethanol administration group (EtOH), low-dose Lf treatment group (LLf), and high-dose Lf group (HLf). In the last three groups, chronic ALI was induced by administering 20% ethanol ad libitum for 12 weeks. Mice in the CON and EtOH groups were fed with AIN-93G diet. Meanwhile, 0.4% and 4% casein in the AIN-93G diet were replaced by Lf as the diets of LLf and HLf groups, respectively. HLf significantly reduced hepatic triglyceride content and improved pathological morphology. HLf could inhibit cytochrome P450 2E1 overexpression and promote alcohol dehydrogenase-1 expression. HLf activated protein kinase B and AMP-activated protein kinase (AMPK), as well as upregulating nuclear-factor-erythroid-2-related factor-2 expression to elevate hepatic antioxidative enzyme activities. AMPK activation also benefited hepatic lipid metabolism. Meanwhile, HLf had no obvious beneficial effects on gut microbiota. In summary, Lf could alleviate chronic ALI in female mice, which was associated with redox balance and lipid metabolism regulation.

Lactoferrin Alleviates Ethanol-Induced Injury via Promoting Nrf2 Nuclear Translocation in BRL-3A Rat Liver Cells

“…Further, the Lf treatment could reduce ethanol-induced cytotoxicity and intracellular ROS accumulation (Figure 3). Similar to the animal experiments [5][6][7], Lf also exhibited preventive effects on ALI in vitro.…”

“…Our previous studies have confirmed that Lf can prevent ALI in mice, and the mechanisms are associated with hepatic redox homeostasis regulation [5][6][7]. Nuclear factor E2-related factor 2 (Nrf2) is a central regulator for redox balance, and our animal experiments highlighted the key role of Nrf2 in Lf-mediated ALI prevention [6,7]. Besides our studies, other research groups have also indicated that Lf treatment is linked to Nrf2 activation in different organs or cells [8][9][10][11].…”

“…Lactoferrin (Lf), mainly derived from bovine milk, is an iron-binding protein with various biological activities [3,4]. Our previous studies have confirmed that Lf can prevent ALI in mice, and the mechanisms are associated with hepatic redox homeostasis regulation [5][6][7]. Nuclear factor E2-related factor 2 (Nrf2) is a central regulator for redox balance, and our animal experiments highlighted the key role of Nrf2 in Lf-mediated ALI prevention [6,7].…”

ASPP2 deficiency attenuates lipid accumulation through the PPARγ pathway in alcoholic liver injury

“…A study found that ethanol can promote fatty acid synthesis, which is characterized by signi cant upregulation of the protein expression of ACC and FAS 22 . Simultaneously, ethanol also reduced the protein level of CPT1A, a key enzyme of fatty acid β-oxidation 23 . Some studies have also found that ethanol can promote the uptake of more fatty acids by hepatocytes 24 .…”

Hesperidin ameliorates H2O2-induced bovine mammary epithelial cell oxidative stress via the Nrf2 signaling pathway

“…In addition, our results indicated that hesperidin may play a protective role in bMECs through the Keap1/Nrf2/ARE signaling pathway. The Keap1/Nrf2/ARE signaling pathway is a key regulator of cellular antioxidant defense [ 44 , 45 ]. Keap1 is a negative regulator of Nrf2 that binds to Nrf2 and retains it in the cytoplasm [ 46 ].…”