Protocatechuic acid mitigates CuO nanoparticles-induced toxicity by strengthening the antioxidant defense system and suppressing apoptosis in liver cells

Due to exceptional properties, copper oxide nanoparticles (CuO NPs) are now being applied in diverse fields such as agriculture, cosmetics, food industry, and medicine. There is enough scientific evidence that CuO NPs are toxic to living organisms. However, no effective method is available to mitigate the health hazard of the CuO NPs. This study aimed to investigate the possible cytoprotective mechanism of protocatechuic acid (PCA) from the toxicity of CuO NPs in human liver HepG2 cells and primary rat hepatocytes. CuO NPs were synthesized by a facile hydrothermal method. X-ray diffraction and electron microscopy characterization data confirmed the formation of spherical and crystalline CuO NPs with smooth surface morphology. On the basis of preliminary results, cells are divided into four groups; (i) control group, (ii) PCA group (10 µg/mL, a non-cytotoxic dose), (iii) CuO NPs group (IC50), and (iv) co-exposure group (PCA + CuO NPs). Results show that pre-treatment with PCA significantly abrogates the CuO NPs-induced cytotoxicity and lactate dehydrogenase leakage in both types of cells. CuO NPs-induced reactive oxygen species, hydrogen peroxide, and malondialdehyde levels are remarkably mitigated by the PCA pre-treatment. The depletion in glutathione and several antioxidant enzymes (e.g. glutathione peroxidase, superoxide dismutase, and catalase) because of the CuO NPs exposure is effectively restored by PCA. Caspase-3 gene up-regulation and mitochondrial membrane potential depletion due to CuO NPs exposure are also alleviated by the pre-treatment using PCA. Therefore, this first study reports the mitigating potential of PCA against CuO NPs toxicity in liver cells by restoring the antioxidant defense system and quashing the apoptosis.