Thymoquinone reduced RIPK1-dependent apoptosis caused by valproic acid in rat brain

Authors

  • Deniz Tastemir Korkmaz Department of Medical Biology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey
  • Sebile Azirak Vocational School of Health Services, Adiyaman University, Adiyaman, Turkey
  • Sedat Bilgic Vocational School of Health Services, Adiyaman University, Adiyaman, Turkey
  • Dilek Bayram Department of Histology and Embryology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
  • Mehmet Kaya Ozer Department of Pharmacology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey

Keywords:

Apoptosis, RIPK1, thymoquinone, valproic acid

Abstract

Aim: Valproic acid (VPA) is a commonly used antiepileptic drug and known to have a neurotoxic effect, but its mechanism is not yet understood. In the present study, we aimed to determine how the VPA causes cell death in the brain and to evaluate the protective effects of thymoquinone (TQ) on VPA-induced brain damage.
Materials and Methods: Male Sprague–Dawley albino rats were divided into three groups: control, VPA (500 mg/kg/day) and VPA + TQ (500 mg/kg/day + 50 mg/kg/day) with seven rats in. At the end of the experiment, rats were sacrificed and brain samples were taken to measure the expression levels of Receptor-interacting serine/threonine-protein kinase-1 (RIPK1) and -3 (RIPK3) genes by quantitative real-time PCR (qRT-PCR), NADPH oxidase-4 (NOX4) and, caspase-3 (CAS-3) expression by immunohistochemistry and the structural changes in the brain tissue by histologically.
Results: RIPK1 gene expression levels were significantly increased in the VPA group compared to the controls (p<0.05) and a decrease in VPA + TQ group against the VPA group. Also, NOX-4 and CAS-3 production were increased in the VPA group compared to the control group (p<0.05), and there is a markedly decrease in the VPA + TQ group compared to the VPA group.
Conclusion: VPA induced RIPK1-dependent apoptosis, leading to cell deaths in the brain and TQ reduced its effects. Therefore, TQ
uptake can be a supportive treatment method for long-term and high-dose VPA users to eliminate undesirable effects.

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Published

2021-11-24

How to Cite

Korkmaz, D. T., Azirak, S., Bilgic, S., Bayram, D., & Ozer, M. K. (2021). Thymoquinone reduced RIPK1-dependent apoptosis caused by valproic acid in rat brain. Annals of Medical Research, 28(11), 2005–2011. Retrieved from https://annalsmedres.org/index.php/aomr/article/view/3967

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