Hesperidin Reverses Oxidative Stress-Induced Damage in Kidney Cells by Modulating Antioxidant, Longevity, and Senescence-Related Genes

<b>Background:</b> Oxidative stress arises from an imbalance between excessive oxidant production and impaired antioxidant defense systems. This imbalance leads to biomolecular damage, contributing to aging and age-related diseases such as chronic kidney disease (CKD). Oxidative stress is a well-established risk factor for CKD and has been reported to accelerate disease progression. Hesperidin, a flavanone glycoside abundant in citrus fruits, exhibits antioxidant, anti-hypertensive, and anti-inflammatory properties and has been suggested to attenuate CKD progression. However, its potential role in reversing oxidative damage in kidney cells remains unclear. <b>Methods:</b> This study aimed to investigate whether hesperidin can reverse oxidative damage in human kidney proximal tubular epithelial (HK-2) cells. Oxidative stress was induced by exposing HK-2 cells to 500 μM hydrogen peroxide (H₂O₂) for 6 h, followed by treatment with 100 μM hesperidin for 24 h. <b>Results:</b> Our results showed that hesperidin significantly ameliorated H₂O₂-induced cytotoxicity. In the hesperidin post-treatment group (H₂O₂ + hesperidin), the expression of the antioxidant gene manganese superoxide dismutase (MnSOD) and the longevity-associated gene sirtuin 1 (SIRT1) was upregulated, while the expression of the senescence-associated gene β-galactosidase was downregulated compared to the H₂O₂-only treatment. <b>Conclusions:</b> These findings suggest that hesperidin promotes recovery from oxidative injury in kidney cells by enhancing antioxidant and longevity pathways and reducing cellular senescence. This may contribute to improved renal health and potentially slow CKD progression in patients suffering from oxidative stress-related kidney damage.