Abstract
Background: Iron overload is a pathological condition characterized by excessive iron deposition in the liver, leading to severe oxidative damage and the progression of hepatic diseases. Recently, ferroptosis—an iron-dependent form of cell death driven by lipid peroxidation—has been identified as a major factor in liver injury caused by iron toxicity. Ferulic acid (FA) is a natural phenolic compound widely recognized for its potent antioxidant and anti-inflammatory properties.
Objective: This study aims to evaluate the hepatoprotective effects of ferulic acid against liver injury and ferroptosis induced by iron overload in mice, while exploring the underlying molecular mechanisms related to iron metabolism.
Method: Thirty healthy Swiss albino mice were randomly assigned to five groups: normal control, iron overload induction (100 mg/kg/day iron dextran IP for 4 weeks), two treatment groups receiving the same iron dose alongside oral FA (50 or 100 mg/kg/day) from day 7 for 3 weeks, and an FA-only control group. The evaluation included liver enzymes (AST), serum and tissue iron levels, oxidative stress markers (MDA, GSH), inflammatory cytokines (IL-6), and iron regulatory proteins (hepcidin via ELISA and ferroportin).
Results: The iron overload induction group showed a significant deterioration compared to the normal control, evidenced by a marked increase in serum and tissue iron levels, elevated AST, and heightened IL-6 concentrations. Additionally, the induction group exhibited severe oxidative stress (increased MDA and depleted GSH), alongside upregulated hepcidin and downregulated ferroportin levels. In contrast, treatment with ferulic acid demonstrated highly positive and protective outcomes. Compared to the untreated induction group, FA administration significantly reduced serum and tissue iron accumulation, lowered AST and IL-6 levels, and restored the antioxidant balance by decreasing MDA and elevating GSH. Furthermore, FA successfully modulated iron metabolism by reducing hepcidin levels and increasing ferroportin expression.
Conclusion: Ferulic acid exhibits a hepatoprotective effect against iron overload-induced ferroptosis. By effectively reversing oxidative stress, inflammation, and iron dysregulation, FA represents a highly promising therapeutic agent for managing iron-related hepatic disorders.
| Intend to be published in the IJPS ? | Yes |
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| Has the manuscript been published | not published |
