Flavonoids for hepatoprotection: Potential natural approaches to mitigate doxorubicin-induced liver toxicity: A mini review

Doxorubicin is a highly efficacious anticancer agent. However, its clinical application is hampered by its detrimental side effects, notably hepatotoxicity. The molecular mechanisms underlying doxorubicin-induced hepatotoxicity encompass the generation of oxidative stress, inhibition of the topoisomerase II enzyme, and the induction of cell necrosis and apoptosis. Excessive exposure to doxorubicin can precipitate acute and chronic liver toxicity. To mitigate this issue, natural products, specifically flavonoids, have been extensively investigated in cellular, animal, and human models to elucidate their potential in alleviating doxorubicin-induced hepatotoxicity. This review comprehensively elucidates the hepatoprotective properties of various flavonoids, such as rutin, apigenin, quercetin, luteolin, hesperidin, naringenin, and genestein, against the adverse effects of doxorubicin administration. The proposed mechanisms by which flavonoids confer hepatoprotective effects encompass their antioxidant capacity to neutralize oxidative stress, modulation of topoisomerase II enzyme activity, and inhibition of apoptotic and necrotic signaling pathways. Furthermore, flavonoids are known to regulate diverse cellular signaling cascades implicated in doxorubicin-induced liver injury, such as inflammatory pathways, endoplasmic reticulum stress, and oxidant-antioxidant balance regulation.