Curcumin Attenuates Aroclor 1254-Induced Oxidative, Genotoxic, and Apoptotic Alterations in HepG2 Cells

Polychlorinated biphenyls (PCBs), particularly Aroclor 1254 (A1254), are persistent environmental contaminants with hepatotoxic, genotoxic, and pro-oxidant properties. The liver, as the main organ for xenobiotic metabolism, is highly vulnerable to PCB-induced oxidative stress and DNA damage. Curcumin, a polyphenolic compound from Curcuma longa, exhibits potent antioxidant, anti-inflammatory, and cytoprotective effects. This study investigated the oxidative, genotoxic, apoptotic, and mutagenic effects of A1254 in HepG2 cells and evaluated curcumin's protective potential. Cells were exposed to sub-cytotoxic concentrations of A1254 (2.5-25 µM), curcumin (0.5-2 µM), and their combinations. ROS levels, antioxidant enzyme activities, oxidative biomarkers, and total antioxidant capacity were measured. DNA damage was assessed via 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-oxoguanine glycosylase (OGG1), and Comet assays. Apoptosis was evaluated by caspase-3 and -8 activities, and mutagenicity via Ames (TA98/TA100) and HPRT assays. A1254 disrupted redox homeostasis, elevating ROS and oxidative damage while depleting glutathione, thiols, and enzymatic antioxidants. Curcumin co-treatment restored antioxidant defenses and mitigated oxidative damage. Genotoxicity induced by A1254, indicated by increased 8-OHdG and DNA strand breaks, was markedly reduced by curcumin, which also attenuated apoptotic responses. These results demonstrate that A1254 exerts multifaceted cytotoxicity via oxidative stress, DNA damage, apoptosis, and mutagenicity, and that curcumin effectively ameliorates these effects, supporting its potential as a hepatoprotective and genoprotective agent against PCB-induced toxicity.