Unlabelled: Acetaminophen-induced liver injury (AILI) is a significant health problem and represents the most frequent cause of drug-induced liver failure in the United States. The development and implementation of successful therapeutic intervention strategies have been demanding, due to significant limitations associated with the current treatment for AILI. Lactoferrin (Lac), a glycoprotein present in milk, has been demonstrated to possess a multitude of biological functions. Our study demonstrated a profound protective effect of Lac in a murine model of AILI, which was not dependent on its iron-binding ability, inhibition of acetaminophen (APAP) metabolism, or a direct cytoprotective effect on hepatocytes. Instead, Lac treatment significantly attenuated APAP-induced liver sinusoidal endothelial cell dysfunction and ameliorated hepatic microcirculation disorder. This protective effect of Lac appeared to be dependent on hepatic resident macrophages (Kupffer cells [KCs]).
Conclusion: Collectively, our data indicate that Lac, through activation of KCs, inhibited APAP-induced liver sinusoidal endothelial cell damage and improved hepatic congestion, thereby protecting against AILI. These findings reveal the significant therapeutic potential of Lac during AILI and other types of liver diseases.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908515 | PMC |
| http://dx.doi.org/10.1002/hep.23476 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Saikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP-SNARE complex assembly in protective autophagy.
Phytomedicine
January 2025
School of Chinese Materia Medica, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing 100029, China. Electronic address:
Background: Radix Bupleuri (RB) and acetaminophen (APAP) are two popular medications having potential hepatotoxicity and substantial risks of irrational co-administration and excessive use, posing an overlooked danger of drug-induced liver injury (DILI). Autophagy is a protective mechanism against APAP-induced DILI, yet, saikosaponin d (SSd) in RB has been characterized to regulate autophagy, although the current findings are controversial.
Purpose: We aim to elucidate whether SSd promoted APAP-induced liver injury by regulating autophagy.
Aculeapyridones A-Q, Pyranopyridone Alkaloids with Protective Effects against Acetaminophen-Induced Acute Liver Injury Discovered from a Coculture of WHUF0198 and a sp.
J Nat Prod
January 2025
Department of Nephrology, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, People's Republic of China.
In the search for novel natural products with hepatoprotective effects against acetaminophen-induced acute liver injury, the marine-derived fungus WHUF0198 was investigated. Seventeen undescribed pyranopyridone alkaloids, aculeapyridones A-Q (-), were isolated by bioactivity-guided fractionation of an extract obtained by coculture of the WHUF0198 with the mangrove-associated fungus sp. DM27.
View Article and Find Full Text PDFScopoletin alleviates acetaminophen-induced hepatotoxicity through modulation of NLRP3 inflammasome activation and Nrf2/HMGB1/TLR4/NF-κB signaling pathway.
Int Immunopharmacol
January 2025
Key Laboratory of Natural Medicines of Changbai Mountain, Ministry of Education, Yanbian University, Yanji, Jilin 133002, China. Electronic address:
Scopoleitin (SP), a bioactive compound from many edible plants and fruits, exerts a wide range of biological activities, however the role and mechanism of SP in acetaminophen (APAP)-induced hepatotoxicity remains unclear. In this study, we verified the protective effect of SP on APAP-induced liver injury (AILI) hepatotoxicity and explore the underlying molecular mechanisms. Here, we showed that SP alleviated AILI by reducing serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, hepatic histopathological damage, inflammation, and liver cell apoptosis.
View Article and Find Full Text PDFSW033291 promotes liver regeneration after acetaminophen-induced liver injury in mice.
Biochem Biophys Res Commun
January 2025
College of Pharmacy, Xinjiang Medical University, Urumqi, 830054, Xinjiang, China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China. Electronic address:
Acetaminophen (APAP) is a commonly utilized antipyretic and analgesic drug. Overdose of APAP is a primary contributor to drug-induced liver injury and acute liver failure (ALF). SW033291 has been shown to play a role in tissue regeneration in various diseases; however, its potential to facilitate liver regeneration following APAP-induced hepatic injury remains unexamined.
View Article and Find Full Text PDFMechanistic insights of methylcinnamate in improving oxidative stress and inflammation in acetaminophen-induced hepatotoxic mice by upregulating Nrf2 pathway.
J Pharm Pharmacol
January 2025
Faculty of Production and Power Engineering, University of Agriculture in Krakow, Balicka 116B, 30-149 Krakow, Poland.
Background: Methylcinnamate (MC), a safe flavoring agent naturally found in Occimum basilicum L. is reported to have an anti-inflammatory responses in various disease models. Acetaminophen (APAP) toxicity is a significant contributor to acute liver injury, which leads to oxidative stress and inflammation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!