Galangin mitigates iron overload-triggered liver injury: Up-regulation of PPARγ and Nrf2 signaling, and abrogation of the inflammatory responses

Aim: Hepatotoxicity is a critical consequence of the iron overload conditions such as hemochromatosis and blood transfusion-requiring anemia. Iron induces hepatotoxicity largely through disruption of cellular redox homeostasis and induction of inflammatory responses. The present work explored the hepatoprotective activity of the bio-active flavone galangin against iron-evoked hepatotoxicity. Main methods: Iron overload model was established in male Wistar rats via intraperitoneal injection of 150 mg/kg iron-dextran subdivided over a ten-day experimental period. Galangin was administered in a daily oral dose of 15 mg/kg throughout the experimental period. Blood and liver tissue samples were collected on day eleven and subjected to biochemical and molecular investigations. Key findings: Galangin significantly reduced liver iron content and serum ferritin level, and alleviated the ironevoked oxidative stress. It enhanced the liver cell integrity as reflected by decreased serum activity of the liver enzymes. Mechanistically, galangin up-regulated the redox-regulating transcription factor Nrf2 and its responsive proteins HO-1 and NQO1. Interestingly, galangin up-regulated the antioxidant and anti-inflammatory protein PPAR gamma and serum hepcidin levels under the iron overload conditions. Equally important, it diminished the nuclear shift of the inflammatory transcription factor NF-cB p65 and down-regulated the levels of the proinflammatory cytokines TNF-alpha and IL-1(i. Significance: The results of the present study highlight the mitigating activity of galangin against iron-induced hepatotoxicity. The study accentuated targeting of Nrf2, PPAR gamma, and NF-cB signaling as potential contributing mechanisms. While clinical studies are still required, the current study supports the possible implementation of galangin in controlling iron overload-associated hepatotoxicity.

Automated summary

The study demonstrated that galangin has a significant protective effect against iron-induced hepatotoxicity, reducing liver iron content, serum ferritin level, and oxidative stress. Galangin exerts its effects through various mechanisms, including up-regulation of Nrf2, PPAR gamma, and down-regulation of NF-cB signaling pathways.