1. Lactoferrin as a therapeutic agent for attenuating hepatic stellate cell activation in thioacetamide-induced liver fibrosis.
- Author
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Pu TY, Chuang KC, Tung MC, Yen CC, Chen YH, Cidem A, Ko CH, Chen W, and Chen CM
- Subjects
- Animals, Male, Rats, Cell Line, Rats, Sprague-Dawley, Liver drug effects, Liver pathology, Liver metabolism, Oxidative Stress drug effects, Reactive Oxygen Species metabolism, Transforming Growth Factor beta1 metabolism, Signal Transduction drug effects, Thioacetamide, Hepatic Stellate Cells drug effects, Hepatic Stellate Cells metabolism, Hepatic Stellate Cells pathology, Lactoferrin pharmacology, Lactoferrin therapeutic use, Liver Cirrhosis chemically induced, Liver Cirrhosis drug therapy, Liver Cirrhosis pathology, Liver Cirrhosis metabolism
- Abstract
Liver fibrosis is a chronic liver disease caused by prolonged liver injuries. Excessive accumulation of extracellular matrix replaces the damaged hepatocytes, leading to fibrous scar formation and fibrosis induction. Lactoferrin (LF) is a glycoprotein with a conserved, monomeric signal polypeptide chain, exhibiting diverse physiological functions, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, and antitumoral activities. Previous study has shown LF's protective role against chemically-induced liver fibrosis in rats. However, the mechanisms of LF in liver fibrosis are still unclear. In this study, we investigated LF's mechanisms in thioacetamide (TAA)-induced liver fibrosis in rats and TGF-β1-treated HSC-T6 cells. Using ultrasonic imaging, H&E, Masson's, and Sirius Red staining, we demonstrated LF's ability to improve liver tissue damage and fibrosis induced by TAA. LF reduced the levels of ALT, AST, and hydroxyproline in TAA-treated liver tissues, while increasing catalase levels. Additionally, LF treatment decreased mRNA expression of inflammatory factors such as Il-1β and Icam-1, as well as fibrogenic factors including α-Sma, Collagen I, and Ctgf in TAA-treated liver tissues. Furthermore, LF reduced TAA-induced ROS production and cell death in FL83B cells, and decreased α-SMA, Collagen I, and p-Smad2/3 productions in TGF-β1-treated HSC-T6 cells. Our study highlights LF's ability to ameliorate TAA-induced hepatocyte damage, oxidative stress, and liver fibrosis in rats, potentially through its inhibitory effect on HSC activation. These findings suggest LF's potential as a therapeutic agent for protecting against liver injuries and fibrosis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2024
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