Protection of Fulvic Acid Against 5-Fluorouracil-induced Intestinal Injury in Mice
Lei Wang1, Weifeng Dai1, Cheng Yuan1
1Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.
Introduction:
Fulvic acid (FA) is a mineral-based traditional Chinese medicine, which is commonly used to treat gastrointestinal diseases. The aim of this study is to investigate the protective effects of FA against 5-FU-induced intestinal injury in vivo and elucidate its potential mechanisms.
Methods:
Mice are randomly divided into 8 groups, including a control group, a model group, PPI treated group (omeprazolea, positive drug), LPDA treated group (loperamidean, positive drug), and four doses (25 mg/kg, 50 mg/kg, 100 mg/kg, 150 mg/kg) of FA treated groups (FA-25, FA- 50, FA-100, FA-150). Histopathological examinations were carried out to assess the protective impact of FA. Transcriptome sequencing, qPCR (quantitative PCR), and western blot analyses were conducted to explore the mechanism of FA.
Results:
Intragastric administration of 5 g/kg FA did not cause acute toxicity in mice. Histopathological examination of the mouse small intestine showed that FA-treated groups had improved morphology. Transcriptome sequencing revealed 69 DEGs that were significantly different between the FA-treated group and the model group. KEGG pathway analysis revealed that these genes were predominantly associated with the cytokine-cytokine receptor interaction pathway. qPCR validation confirmed the expression profiles of crucial differentially expressed genes, specifically Csf3r, Csf2rb, and Csf2rb2. Western blot analysis confirmed the Csf3r and Csf2rb protein expression results.
Discussion:
This study suggests that FA protects against 5-FU-induced intestinal injury and is associated with upregulation of granulocyte-related gene expression.
Conclusion:
These observations suggest that FA has a protective effect against 5-FU-induced intestinal injury. However, these findings are still preclinical, and their therapeutic potential remains to be further validated in large-animal models and human cell-based systems.
