Naringenin Inhibit the Hydrogen Peroxide-Induced SH-SY5Y Cells Injury Through Nrf2/HO-1 Pathway

• Published in: Neurotoxicity research 2019-11, Vol.36 (4), p.796-805
• Main Authors: Jin, Yuzi, Wang, Hua
• Format: Article
• Language: English
• Subjects: Antioxidants - pharmacology; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Line, Tumor; Cell Survival - drug effects; Flavanones - pharmacology; Heme Oxygenase-1 - metabolism; Humans; Hydrogen Peroxide - toxicity; Membrane Potential, Mitochondrial - drug effects; Neurobiology; Neurochemistry; Neurology; Neuroprotective Agents - pharmacology; Neurosciences; NF-E2-Related Factor 2 - metabolism; Original Article; Pharmacology/Toxicology; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects
• ISSN: 1029-8428; 1476-3524
• DOI: 10.1007/s12640-019-00046-6

Naringenin (NGN), a flavonoid, abundantly present in citrus fruits, has been established as a neuroprotective agent. However, the precise protective mechanisms remain worthy of further investigation. The present study was designed to explore the protective effects of NGN against hydrogen peroxide (H 2 O 2 )-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and the possible mechanisms involved. Exposure of cells to 400 μM H 2 O 2 for 2 h caused viability loss, apoptotic increase, and reactive oxygen species (ROS) increase, pre-treatment with NGN for 12 h significantly reduced the viability loss, apoptotic rate, and attenuated H 2 O 2 -mediated ROS production. In addition, NGN inhibited H 2 O 2 -induced mitochondrial dysfunctions, including lowered membrane potential, decreased Bcl-2/Bax ratio, cytochrome c release, and the cleavage of caspase-3. We also showed that NGN increased HO-1 expression. NGN treatment caused nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2). NGN activated both ERK and PI3 K/Akt, and treatments with the specific ERK inhibitor PD98059, the PI3 K inhibitor LY294002, and the specific Nrf2 shRNA suppressed the NGN-induced HO-1 expression. The HO-1 inhibitor ZnPP abolished the neuroprotective effect of NGN against H 2 O 2 -induced neurotoxicity. Taken together, the present study demonstrates that regulation of Nrf2/HO-1 pathway through activation of ERK and PI3 K/Akt, and the inhibition of mitochondria-dependent apoptosis together may render NGN protect SH-SY5Y cells from H 2 O 2 -induced neurotoxicity.