The Effect of Hesperidin on Inflammatory Response and Oxidant–Antioxidant Systems in Benzo[a]pyrene-Exposed Non-Small Cell Lung Cancer (A549) Cells

Lung cancer represents a substantial global oncology burden, exhibiting mortality rates that surpass those of prostate, pancreatic, and breast cancers. Extensive research has established a correlation between exposure to polycyclic aromatic hydrocarbon mixtures—particularly those containing benzo(a)pyrene (BaP)—and elevated risks of pulmonary and dermal malignancies across various species, including humans. Hesperidin (HSP), a prominent bioactive flavonoid found in citrus fruits and medicinal herbs such as Hypericum perforatum, is recognized for its diverse pharmacological properties. The present study aimed to elucidate the antioxidant and anti-inflammatory efficacy of HSP against BaP-induced toxicity in the A549 non-small cell lung cancer (NSCLC) cell line. Following the determination of application concentrations via MTT assay, the modulatory effects of HSP on cellular proliferation, oxidative stress markers (TAS, TOS, and OSI), and key pro-inflammatory cytokines (TNF−α, IL−1β, and TGF−β) were systematically evaluated. Isolated exposure to BaP predominantly triggered a targeted upregulation of IL-1β; however, hesperidin demonstrated unexpected pro-oxidant dynamics, characterized by a substantial drop in TAS alongside a concurrent elevation in both TOS and OSI profiles, especially at maximum-dose concentrations. Notably, combining BaP with this heightened hesperidin regimen manifested the most severe oxidative distress phenotype, implying a synergistic pro-oxidant cascade between the two agents. On the contrary, minimized concentrations of hesperidin exerted explicit cytoprotective mitigation against the BaP-induced surge in IL-1β, thereby confirming a highly delicate and narrow therapeutic index for this flavonoid.