Myricetin protects against doxorubicin-induced liver damage by modulating oxidative and inflammatory pathways
摘要
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.
MethodsThis 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.
ResultsDox 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.
ConclusionMyricetin demonstrated protective effects against Dox-induced liver damage through its antioxidant and anti-inflammatory properties. Further research is warranted.