The effects of acrylamide-mediated dorsal root ganglion neurons injury on ferroptosis

• Published in: Human & experimental toxicology 2022-09, Vol.41, p.9603271221129786-9603271221129786
• Main Authors: An, Shuai, Shi, Jingfei, Li, Zheng, Feng, Mingli, Cao, Guanglei
• Format: Article
• Language: English
• Subjects: Acrylamide; Brain-derived neurotrophic factor; Cell migration; Cell proliferation; Central nervous system; Dorsal root ganglia; Ferroptosis; Ganglia; Glial cell line-derived neurotrophic factor; Glial cells; Glutathione; Growth factors; Iron; Nerve growth factor; Nerves; Neuronal-glial interactions; Neurons; Neurotoxicity; Reactive oxygen species; Schwann cells; Therapeutic targets; Vascular endothelial growth factor
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/09603271221129786

Acrylamide (ACR) is a water-soluble chemical applied in industrial and laboratory processes. The neurotoxicity induced by acrylamide involves both peripheral and central nervous system. Hence, there is a growing urgency to investigate the mechanisms of acrylamide-induced neurotoxicity and search novel therapeutic target for the nerve repair. The effects of ACR on the proliferation, reactive oxygen species (ROS) and iron production of dorsal root ganglia (DRG) neurons and Schwann cells were determined. 5-Ethynyl-2′-deoxyuridine (EDU) staining and transwell assay were applied to detect the proliferation and migration capacity of DRG cells. Ferrostatin-1 (Fer-1) was used to suppress ferroptosis induced by ACR. RT-PCR analysis was performed to examine the expression of neurotrophic factors including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and glial cell line-derived neurotrophic factor (GDNF). Moreover, Iron, ROS, malondialdehyde (MDA) and glutathione (GSH) contents were measured to reveal the regulation of ferroptosis in ACR-related nerve injury. ACR inhibited the proliferation and migration of DRG neurons and the supplementation of Fer-1 reversed the effects induced by ACR. Besides, the treatment of Fer-1 effectively increased the expression of NGF, BDNF, VEGF and GDNF. Furthermore, ACR increased the iron level, MDA and ROS contents while inhibited the level of GSH. It was unveiled that ACR attenuated the proliferation, migration and neuron repair of DRG neurons through regulating ferroptosis. The modulation of ferroptosis might be a promising therapeutic strategy and provide references for future treatment of acrylamide-induced nerve damage.