Quercetin alleviates styrene oxide-induced cytotoxicity in cortical neurons in vitro via modulation of oxidative stress and apoptosis

Abstract

Styrene 7,8-oxide (SO) is the principal metabolite of styrene, an industrial neurotoxic compound which causes various neurodegenerative disorders. The present study aimed to explore the mechanisms of SO cytotoxicity (0.5 − 4 mM) in primary cortical neurons and to evaluate the neuroprotective potential of quercetin (QUER). Our results showed that exposure to SO decreased viability of cortical neurons in a concentration-dependent manner. In the presence of QUER, cell viability was increased significantly. The neuroprotective effects of QUER were associated with the reduction of intracellular Reactive Oxygen Species (ROS), the decrease in calcium overload and the restoration of mitochondrial membrane depolarization caused by SO. Additionally, to evaluate neuronal death mechanisms triggered by SO, cells were incubated with Ac-DEVD-CHO, Calpeptin and Necrostatin-1, pharmacological inhibitors of caspase-3, calpains and necroptosis respectively. The data showed that the three inhibitors reduced cell death induced by SO and suggested the implication of apoptotic, necrotic and necroptotic pathways. However, western blot analysis showed that QUER attenuated the activation of caspase-3 but did not prevent calpain activity. Taken together, these data indicated that the cytotoxicity of SO was mediated by oxidative stress and apoptosis, necrosis and necroptosis mechanisms, while the neuroprotection provided by QUER against SO depended mainly on its anti-apoptotic activity.

Graphical Abstract

Keywords:

• Styrene oxide
• quercetin
• oxidative stress
• apoptosis
• necrosis
• necroptosis

Acknowledgements

We are thankful to Prof. Carlos Matute, from the Instituto Del pays Vasco, Spain, for giving us the opportunity to carry out these studies in his laboratory.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The present research was financially supported by Tunisian Ministry of Higher Education and Scientific Research.