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The protective effect of apigenin against inorganic arsenic salt-induced toxicity in PC12 cells

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Abstract

Poisoning by arsenic affects people worldwide, and many human illnesses and health issues, including neurotoxicity, have been linked to chronic exposure to arsenic. When exposed to arsenic, the body produces intracellular reactive oxygen species (ROS), which influence a variety of alterations in cellular activity and directly harm molecules through oxidation. Arsenic-induced lesions are improved by antioxidants with the ability to lower ROS levels. Therefore, the current research aimed to assess how well apigenin protected PC12 cells from the toxicity caused by inorganic arsenic salt (iAs). For 24 and 48 h, iAs and/or apigenin were applied to PC12 cells. Then, oxidative stress indicators like malondialdehyde (MDA), nitric oxide (NO), and ROS in addition to the enzymatic and non-enzymatic antioxidant molecules such as catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) were assessed. Moreover, after exposure to iAs, PC12 was examined for nuclear factor erythroid 2–related factor 2 (Nrf2) expression to clarify how apigenin manifests its neuroprotection. Furthermore, NF-kB p65 concentration and IL-1B, IL-6, and TNF-α mRNA expression were measured to assess neuroinflammation. Bax, caspase-3, and Bcl-2 levels were measured to investigate apigenin's potential to protect PC12 cells from iAs poisoning. The obtained results revealed that, the cell survival rate in the iAs group was significantly lower (P < 0.05), and the number of viable cells steadily increased after apigenin treatment. Furthermore, the study found that iAs decreased GSH, CAT, and SOD in the PC12 cells while increasing ROS, MDA, and NO levels. In PC12 cells, the capacity of iAs to cause oxidative stress was linked to the induction of neuroinflammation and apoptosis. Interestingly, apigenin pre-treatment of PC12 cells resulted in exceptional protection against iAs-induced neuroinflammation, oxidative stress, and apoptotic cell death. Nrf2 upregulation in PC12 cells may explain the neuroprotection effect of apigenin against iAs toxicity. In conclusion, the obtained results of the present study have clinical significance and indicate that apigenin is a promising candidate for shielding the nervous system from toxic effects caused by arsenic. These findings require further investigation using in vivo experimental models.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to extend their sincere appreciation to the Researchers Supporting Project number (RSP2023R96), King Saud University, Riyadh, Saudi Arabia.

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The authors would like to extend their sincere appreciation to the Researchers Supporting Project number (RSP2023R96), King Saud University, Riyadh, Saudi Arabia.

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  1. Department of Zoology, College of Science, King Saud University, P.O. Box 2455, 11451, Riyadh, Saudi Arabia

    Rafa Almeer & Nouf M. Alyami

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  1. Rafa Almeer
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R. Almeer and N.M. Alyami designed the project, performed the experiments, and drafted and edited the manuscript. R. Almeer analyzed the data, interpreted the data, supplied the chemicals and reagents, and drafted and edited the manuscript. All authors approved the final draft.

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Almeer, R., Alyami, N.M. The protective effect of apigenin against inorganic arsenic salt-induced toxicity in PC12 cells. Environ Sci Pollut Res 30, 106625–106635 (2023). https://doi.org/10.1007/s11356-023-29884-w

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