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. 2024 Feb 25;51(1):360.
doi: 10.1007/s11033-024-09236-8.

Urolithin B protects PC12 cells against glutamate-induced toxicity

Israa Aljabouri  1 , Mehdi Rostami  1 , Farshad Mirzavi  2 , Mahla Kazemian Kakhki  1 , Abbas Alalikhan  1 , Elaheh Gheybi  1 , Ali Hakimi  1 , Mohammad Soukhtanloo  3   4
Affiliations

Urolithin B protects PC12 cells against glutamate-induced toxicity

Israa Aljabouri et al. Mol Biol Rep. .

Abstract

Background: The involvement of malfunctioning glutamate systems in various central nervous system (CNS) disorders is widely acknowledged. Urolithin B, known for its neuroprotective and antioxidant properties, has shown potential as a therapeutic agent for these disorders. However, little is known about its protective effects against glutamate-induced toxicity in PC12 cells. Therefore, in this study, for the first time we aimed to investigate the ability of Urolithin B to reduce the cytotoxic effects of glutamate on PC12 cells.

Methods: Different non-toxic concentrations of urolithin B were applied to PC12 cells for 24 h before exposure to glutamate (10 mM). The cells were then analyzed for cell viability, intracellular reactive oxygen species (ROS), cell cycle arrest, apoptosis, and the expression of Bax and Bcl-2 genes.

Results: The results of MTT assay showed that glutamate at a concentration of 10 mM and urolithin B at a concentration of 114 μM can reduce PC12 cell viability by 50%. However, urolithin B at non-toxic concentrations of 4 and 8 μM significantly reduced glutamate-induced cytotoxicity (p < 0.01). Interestingly, treatment with glutamate significantly enhanced the intracellular ROS levels and apoptosis rate in PC12 cells, while pre-treatment with non-toxic concentrations of urolithin B significantly reduced these cytotoxic effects. The results also showed that pre-treatment with urolithin B can decrease the Bax (p < 0.05) and increase the Bcl-2 (p < 0.01) gene expression, which was dysregulated by glutamate.

Conclusions: Taken together, urolithin B may play a protective role through reducing oxidative stress and apoptosis against glutamate-induced toxicity in PC12 cells, which merits further investigations.

Keywords: Apoptosis; Cell cycle; Glutamate toxicity; Reactive oxygen species; Urolithin B.

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