Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr;62(4):4631-4640.
doi: 10.1007/s12035-024-04587-6. Epub 2024 Oct 29.

Enoxaparin Protects C6 Glioma Cells from Glutamate-Induced Cytotoxicity by Reducing Oxidative Stress and Apoptosis

Fatih Yulak  1 , Ziad Joha  2 , Ayşegül Öztürk  3 , Zeynep Deniz Şahin İnan  4 , Ahmet Şevki Taşkıran  1
Affiliations

Enoxaparin Protects C6 Glioma Cells from Glutamate-Induced Cytotoxicity by Reducing Oxidative Stress and Apoptosis

Fatih Yulak et al. Mol Neurobiol. 2025 Apr.

Abstract

Recent studies suggest enoxaparin may protect the central nervous system (CNS) from damage. However, its specific effects on glial cells and the underlying mechanisms involving cell death and oxidative stress require further investigation. Therefore, this research investigated enoxaparin's potential to safeguard C6 glioma cells against glutamate-induced cytotoxicity, specifically focusing on its influence on oxidative stress and apoptotic mechanisms. To investigate the neuroprotective effects of enoxaparin against glutamate-induced cytotoxicity in C6 cells, four groups were established: a control group, a group exposed to 10 mM glutamate, a group treated with enoxaparin at concentrations ranging from 25 to 200 µM, and a group receiving both 10 mM glutamate and enoxaparin at concentrations ranging from 25 to 200 µM. Cell viability was measured using an XTT assay. To evaluate the effects of enoxaparin on oxidative stress, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured using ELISA, along with total antioxidant status (TAS) and total oxidant status (TOS). Apoptosis was evaluated using flow cytometry, and caspase-3 activity, a key marker of apoptosis, was assessed using caspase-3 immunofluorescence staining. Enoxaparin at 50, 100, and 200 µM markedly increased cell viability in the enoxaparin + glutamate group. Enoxaparin treatment in the enoxaparin + glutamate group also significantly elevated levels of SOD and TAS, while concurrently decreasing MDA and TOS levels. These changes indicate a reduction in oxidative stress. Enoxaparin treatment further resulted in a significant decline in cleaved caspase-3 levels, a marker of apoptosis. Enoxaparin pre-treatment reduced cell death according to flow cytometry analysis. This study suggests enoxaparin's potential to shield C6 glioma cells from glutamate-induced cell death by mitigating both oxidative stress and apoptotic pathways. More research is needed to confirm this effect.

Keywords: Apoptosis; C6 cells; Cytotoxicity; Enoxaparin; Glutamate; Oxidative stress.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing Interests: The authors declare no competing interests.

References

    1. Dirik H, Joha Z (2023) Investigation of the effect of sugammadex on glutamate-induced neurotoxicity in C6 cell line and the roles played by nitric oxide and oxidative stress pathways. Fundam Clin Pharmacol 37(4):786–793 - PubMed
    1. Balázs R, Bridges RJ, Cotman CW (2005) Glutamate and glutamate receptors in neurological diseases. Excitatory Amino Acid Transmission in Health and Disease 13:1–46
    1. Choi DW (1992) Excitotoxic cell death. J Neurobiol 23(9):1261–1276 - PubMed
    1. Kaplan-Arabaci O, Acari A, Ciftci P, Gozuacik D (2022) Glutamate scavenging as a neuroreparative strategy in ıschemic stroke. Front Pharmacol 23(13):866738
    1. Zott B, Konnerth A (2023) Impairments of glutamatergic synaptic transmission in Alzheimer’s disease. Semin Cell Dev Biol 1(139):24–34

LinkOut - more resources