Syringic acid attenuates chlorpyrifos-induced redox imbalance, mitochondrial depolarization, and apoptosis-related transcriptional changes in HepG2 cells.

Abstract

Chlorpyrifos (CPF) is an organophosphate pesticide associated with hepatocellular toxicity, oxidative stress, and mitochondrial dysfunction. Syringic acid (SA) is a naturally occurring phenolic acid known for its antioxidant and cytoprotective properties. This study evaluated whether SA attenuates CPF-induced injury in HepG2 cells by assessing cytotoxicity, oxidative stress parameters, mitochondrial membrane potential, cell-cycle distribution, and mRNA expression of genes related to antioxidant defense, inflammation, and apoptosis. CPF exposure reduced MTT-derived metabolic activity and increased membrane damage, intracellular oxidant-associated DCF fluorescence, total oxidant status, and malondialdehyde, while decreasing total antioxidant capacity, superoxide dismutase, and glutathione peroxidase activities. CPF also increased mitochondrial depolarization and altered antioxidant-, inflammation-, and apoptosis-related mRNA expression. Co-treatment of SA with CPF attenuated oxidative stress, improved antioxidant-related biochemical parameters, reduced mitochondrial depolarization, and partially normalized these transcriptional changes. These findings indicate that SA attenuates CPF-induced cellular injury in association with improved redox status, preserved mitochondrial membrane potential, and changes in stress-related transcripts.