The effects of epicatechin on oxidative stress and genotoxicity induced by cypermethrin in PC-12 cell line

This study investigated the protective effects of epicatechin against cypermethrin-induced oxidative stress and genotoxicity in PC-12 cells. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay following exposure to cypermethrin (1-300 μM). The IC₅₀ concentration was determined and subsequently used to induce toxicity. PC-12 cells were treated with epicatechin (50, 100, 150, and 200 μM) in the presence of cypermethrin. Intracellular reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and DNA damage were evaluated using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay, biochemical assays, and alkaline comet assay, respectively. Cypermethrin induced concentration-dependent cytotoxicity, reducing cell viability from 107.5% at 1 μM to 40.29% at 300 μM, with an IC₅₀ value of 238.5 ± 6.9 μM. Cypermethrin significantly increased ROS production (83.55%), depleted intracellular GSH (93.00 ± 1.73 to 50.33 ± 1.53 nmol/mg protein), and elevated MDA levels (22.67 ± 2.52 to 81.00 ± 2.00 nmol/mg protein) compared with the control group (p < 0.05). Epicatechin treatment dose-dependently attenuated oxidative stress, restoring GSH levels to 74.67 ± 1.53 nmol/mg protein, reducing MDA levels to 51.00 ± 2.65 nmol/mg protein, and decreasing ROS production to 53.43% at 200 μM. Comet assay analysis demonstrated that cypermethrin significantly increased tail length, percentage DNA in tail, and tail moment, whereas epicatechin (200 μM) markedly reduced all genotoxicity parameters and comet tail formation. Epicatechin protects PC-12 cells from cypermethrin-induced oxidative and genotoxic injury by enhancing antioxidant defenses, limiting lipid peroxidation, and reducing DNA damage. Further in vivo studies are required to confirm its neuroprotective potential and define optimal dosing.