Nephrotoxicity is a major clinical challenge, often triggered by chemotherapeutic agents, environmental toxins, and metabolic imbalances. Its underlying mechanisms-oxidative stress, inflammation, mitochondrial dysfunction, and apoptosis-can lead to irreversible kidney damage. Current treatments offer limited molecular protection, underscoring the need for novel strategies. Quercetin, a bioactive flavonoid abundant in fruits and vegetables, has demonstrated promising nephroprotective properties due to its antioxidant, anti-inflammatory, and anti-apoptotic activities. This review aims to synthesize recent findings on therapeutic role of quercetin in preventing or mitigating nephrotoxicity. A literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar to identify in vitro, in vivo, and clinical studies published between 2021 and 2025 that explored the effects of quercetin on nephrotoxicity. Quercetin enhances renal function by lowering serum creatinine and urea, restoring antioxidant enzymes (SOD, CAT, GPx), and reducing lipid peroxidation. It activates the Sirt1/Nrf2/HO-1 axis to stabilize mitochondria and redox balance, while suppressing NF-κB and pro-inflammatory cytokines (TNF-α, IL-6). Quercetin also engages MAPK/ERK and AKT1 pathways to support cell survival, regulates apoptosis via Bax/Bcl-2 and caspase inhibition, and promotes autophagy through Beclin 1, LC3β, and TFEB activation. These combined effects preserve renal architecture, reduce fibrosis, and improve histological outcomes. Quercetin offers a multi-targeted approach to renal protection, integrating antioxidant, anti-inflammatory, anti-apoptotic, and autophagic mechanisms. Its modulation of key signaling pathways positions it as a strong candidate for adjunctive nephroprotective therapy. Future studies should focus on improving its bioavailability, assessing long-term safety, and exploring synergistic applications in clinical settings.
Yazdanpanah et al. (Mon,) studied this question.