AIM: The aim of our study was to explore the role of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) on the exposure of SiO2 nanoparticles (NPs) and its influence. MATERIALS & METHODS: To understand the mechanism of NP-induced oxidative stress, the involvement of oxidative-stress-responding transcription factors and the Nrf2/antioxidant reactive element (ARE) signaling pathway in the toxicity of SiO2 NPs' exposure was investigated via in vivo and in vitro models. RESULTS: A549 cells showed a significant cytotoxic effect while A549-shNrf2 cells showed decreased cell viability after nm-SiO2 exposure. SiO2 NPs' exposure activated the Nrf2/ARE signaling pathway. Nrf2-/- exposed mice showed increased reactive oxygen species, 8-hydroxyl deoxyguanosine level and decreased total antioxidant capacity. Nrf2/ARE signaling pathway activation disrupted, leading inhibition of heme oxygenase-1 and upregulation of PKR-like endoplasmic-reticulum-regulated kinase. CONCLUSION: Our findings suggested that Nrf2 could protect against oxidative stress induced by SiO2 NPs, and the Nrf2/ARE pathway might be involved in mild-to-moderate SiO2 NP-induced oxidative stress that was evident from dampened activity of Nrf2.
AIM: The aim of our study was to explore the role of nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) on the exposure of SiO2 nanoparticles (NPs) and its influence. MATERIALS & METHODS: To understand the mechanism of NP-induced oxidative stress, the involvement of oxidative-stress-responding transcription factors and the Nrf2/antioxidant reactive element (ARE) signaling pathway in the toxicity of SiO2 NPs' exposure was investigated via in vivo and in vitro models. RESULTS: A549 cells showed a significant cytotoxic effect while A549-shNrf2 cells showed decreased cell viability after nm-SiO2 exposure. SiO2 NPs' exposure activated the Nrf2/ARE signaling pathway. Nrf2-/- exposed mice showed increased reactive oxygen species, 8-hydroxyl deoxyguanosine level and decreased total antioxidant capacity. Nrf2/ARE signaling pathway activation disrupted, leading inhibition of heme oxygenase-1 and upregulation of PKR-like endoplasmic-reticulum-regulated kinase. CONCLUSION: Our findings suggested that Nrf2 could protect against oxidative stress induced by SiO2 NPs, and the Nrf2/ARE pathway might be involved in mild-to-moderate SiO2 NP-induced oxidative stress that was evident from dampened activity of Nrf2.
Authors: Narasimha M Beeraka; Runze Zhou; Xiaoyan Wang; Hemanth Vikram P R; Tegginamath Pramod Kumar; Junqi Liu; M V Greeshma; Subhankar P Mandal; B M Gurupadayya; Ruitai Fan Journal: Int J Nanomedicine Date: 2022-05-12