Apigenin attenuates tetrabromobisphenol A-induced cytotoxicity in neuronal SK-N-MC cells

Abstract

Tetrabromobisphenol A (TBBPA) is a reactive brominated flame retardant widely used in various industrial and household products. This compound is persistent in the environment and accumulates in living organisms through the food chain, and is toxic to animals and human beings. Studies have shown that TBBPA is toxic to various human cell lines, including neuronal cells. Apigenin is a dietary flavonoid that exhibits various beneficial health effects on biological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. This study investigated the cytoprotective effects of apigenin against TBBPA-mediated cytotoxicity in SK-N-MC cells. Our results demonstrated that treatment of SK-N-MC cells with apigenin increased the cell viability, which was decreased by TBBPA, and reduced apoptosis and autophagy induced by TBBPA. Although we did not observe any change in the levels of IL-1β and nitrite in cultured cells after TBBPA treatment, apigenin was found to decrease the production of these pro-inflammatory mediators. Apigenin decreased the intracellular Ca²⁺ concentration, NOX4 level, oxidative stress, and mitochondrial membrane potential loss and increased the mitochondrial biogenesis and nuclear Nrf2 levels that were reduced by TBBPA. Finally, apigenin treatment decreased Akt and ERK induction in cells exposed to TBBPA. Based on these results, apigenin could be a promising candidate for designing natural drugs to treat or prevent TBBPA-related neurological disorders.

Keywords:

• Tetrabromobisphenol A
• apigenin
• SK-N-MC cells
• oxidative stress
• neuroprotection

Conflict of interest

The authors did not report any conflict of interest.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Additional information

Funding

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (Grant Number: HI14C-2700-020014).