2. Academic Validation
  3. Lactoferrin as a therapeutic agent for attenuating hepatic stellate cell activation in thioacetamide-induced liver fibrosis

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

  • Biomed Pharmacother. 2024 May:174:116490. doi: 10.1016/j.biopha.2024.116490.
Tzu-Yu Pu 1,  Kai-Cheng Chuang 1,  Min-Che Tung 2,  Chih-Ching Yen 3,  Yu-Hsuan Chen 1,  Abdulkadir Cidem 4,  Chu-Hsun Ko 1,  Wei Chen 5,  Chuan-Mu Chen 6
Affiliations

Affiliations

  • 1 Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.
  • 2 Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; Department of Surgery, Tungs' Taichung Metro Harbor Hospital, Taichung 435, Taiwan.
  • 3 Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, China Medical University Hospital, and College of Health Care, China Medical University, Taichung 404, Taiwan.
  • 4 Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; Department of Molecular Biology and Genetics, Erzurum Technical University, Erzurum 25250, Turkey.
  • 5 Division of Pulmonary and Critical Care Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan.
  • 6 Department of Life Sciences, and Doctorial Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; The iEGG and Animal Biotechnology Center, and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan. Electronic address: chchen1@dragon.nchu.edu.tw.
PMID: 38554526 DOI: 10.1016/j.biopha.2024.116490
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.

Keywords

Hepatic stellate cells; Lactoferrin; Liver fibrosis; TGF-β1; Thioacetamide.

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