Myricetin protects against doxorubicin-induced liver damage by modulating oxidative and inflammatory pathways

BACKGROUND: Doxorubicin (Dox) is a highly effective chemotherapy drug used to treat various cancers. However, its clinical application is limited by liver toxicity, which is mainly caused by oxidative stress, inflammation, and mitochondrial damage. Myricetin, a natural flavonoid present in many fruits and vegetables, has demonstrated antioxidant and anti-inflammatory activities, making it a potential protective agent against such toxicity. METHODS: This study aimed to evaluate the protective effects of myricetin on Dox-induced liver damage in rats. Thirty-six male Sprague-Dawley rats were divided into six groups: a negative control, a Dox-only group (20 mg/kg, given intraperitoneally on day 10), a myricetin-only group (20 mg/kg, dissolved in corn oil, given orally for 10 days), high-dose (HD) myricetin + Dox (20 mg/kg), low-dose (LD) myricetin + Dox (10 mg/kg), and corn oil control. Biochemical, hematological, oxidative, and histological parameters were evaluated 24 h after Dox injection. RESULTS: Dox increased serum alanine transaminase (75.6 ± 3.2 U/L), aspartate transaminase (237.6 ± 15.3 U/L), alkaline phosphatase (491.3 ± 16.4 U/L), liver-to-body weight ratio (4.38 ± 0.08%), total oxidant status (TOS, about two-fold compared to the control), and TNF-α (9.94 ± 0.82 U/mL), while decreasing total antioxidant capacity (T-AOC) by 35.2%, and bile acids by 24.0%. Myricetin coadministration, especially at higher doses, significantly reversed these changes. Histopathological evaluation confirmed myricetin's hepatoprotective effect, showing attenuation of hepatocellular degeneration, sinusoidal congestion, and inflammatory infiltration. CONCLUSION: Myricetin demonstrated protective effects against Dox-induced liver damage through its antioxidant and anti-inflammatory properties. Further research is warranted.