Lactoferrin as a therapeutic agent for attenuating hepatic stellate cell activation in thioacetamide-induced liver fibrosis

• Published in: Biomedicine & pharmacotherapy 2024-05, Vol.174, p.116490-116490, Article 116490
• Main Authors: Pu, Tzu-Yu, Chuang, Kai-Cheng, Tung, Min-Che, Yen, Chih-Ching, Chen, Yu-Hsuan, Cidem, Abdulkadir, Ko, Chu-Hsun, Chen, Wei, Chen, Chuan-Mu
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Hepatic stellate cells; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - metabolism; Hepatic Stellate Cells - pathology; Lactoferrin; Lactoferrin - pharmacology; Lactoferrin - therapeutic use; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver Cirrhosis - chemically induced; Liver Cirrhosis - drug therapy; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Liver fibrosis; Male; Oxidative Stress - drug effects; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; TGF-β1; Thioacetamide; Transforming Growth Factor beta1 - metabolism
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2024.116490

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. [Display omitted] •LF mitigates TAA-induced liver fibrosis via antioxidant and anti-inflammatory actions.•LF treatment reduces ALT, AST, and fibrosis markers in TAA-induced liver damage.•LF suppresses inflammatory and fibrogenic factors in TAA-treated liver tissues.•LF diminishes ROS production and cell death, offering hepatoprotective effects.•LF inhibits HSC activation, potentially serving as a therapeutic agent for liver fibrosis.