Protection of Fulvic Acid Against 5-Fluorouracil-induced Intestinal Injury in Mice

Area of Science:

• Gastroenterology
• Pharmacology
• Molecular Biology

Background:

• Fulvic acid (FA), a component of traditional Chinese medicine, is utilized for gastrointestinal ailments.
• 5-Fluorouracil (5-FU) is a chemotherapeutic agent known to induce intestinal injury.
• Investigating FA's protective mechanisms against 5-FU-induced enteropathy is crucial.

Purpose of the Study:

• To evaluate the efficacy of Fulvic acid (FA) in mitigating 5-FU-induced intestinal damage in a murine model.
• To elucidate the molecular pathways involved in FA's protective effects against chemotherapy-induced enteritis.

Main Methods:

• Mice were administered varying doses of FA (25-150 mg/kg) or positive controls (omeprazole, loperamide) after 5-FU induction.
• Histopathological analysis assessed intestinal morphology.
• Transcriptome sequencing, qPCR, and Western blot identified key molecular changes, focusing on differentially expressed genes (DEGs) and protein expression.

Main Results:

• Fulvic acid (FA) exhibited no acute toxicity at the tested doses.
• FA treatment significantly improved intestinal morphology in 5-FU treated mice.
• Transcriptome analysis identified 69 DEGs, primarily linked to cytokine-cytokine receptor interactions, with validation of Csf3r, Csf2rb, and Csf2rb2 expression.

Conclusions:

• Fulvic acid (FA) confers protection against 5-FU-induced intestinal injury.
• The protective mechanism involves the upregulation of granulocyte-related genes, including Csf3r and Csf2rb.
• Further validation in preclinical models is warranted to explore FA's therapeutic potential.