Zingerone attenuates sciatic nerve damage caused by sodium arsenite by inhibiting NF-κB, Caspase-3, and ATF-6/CHOP pathways and activating the Akt2/FOXO1 pathway

Document Type : Original Article


1 Department of Orthopedics and Traumatology, Faculty of Medicine, Kütahya Health Sciences University, Kütahya, Turkey

2 Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey

3 Department of Histology and Embryology, Faculty of Medicine, Aksaray University, Aksaray, Turkey

4 Department of Medical Biochemistry, Faculty of Medicine, Aksaray University, Aksaray, Turkey


Objective(s): In the present study, the potential protective effects of zingerone (ZNG) against sciatic nerve damage caused by sodium arsenite (SA), a common environmental pollutant, were evaluated by various biochemical, molecular, and histological methods.
Materials and Methods: In the study, SA and ZNG were given to 35 male Sprague Dawley rats for 14 days. At the end of the period, the sciatic nerve tissues were taken and the markers involved in oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis were analyzed.
Results: The data obtained showed that SA decreased glutathione (GSH) levels and increased malondialdehyde (MDA) levels in the sciatic nerve tissue. However, it was determined that these markers approached the control group levels due to the anti-oxidant properties of ZNG. While SA triggered endoplasmic reticulum stress and apoptosis pathways, ZNG suppressed them. Moreover, SA up-regulated inflammatory markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), and neuronal nitric oxide synthases (nNOS) in the sciatic nerves and caused neuro-inflammation and inhibited cell survival by suppressing serine/threonine-protein kinase 2 (Akt2) and forkhead box protein O1 (FOXO1) genes. It has also been shown histopathologically that SA causes degeneration in the sciatic nerves. In contrast, ZNG suppressed neuro-inflammation, activated Akt2/FOXO1 signaling, and repaired histological irregularities.
Conclusion: In general, SA caused oxidative stress, inflammation, ER stress, and apoptosis in the sciatic nerves of rats, causing damage to the tissues, however, ZNG suppressed these pathways and protected the sciatic nerves from the destructive effect of SA.


Main Subjects

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