Protective effect of CDDO-ethyl amide against high-glucose-induced oxidative injury via the Nrf2/HO-1 pathway.
Intervertebral disc degeneration (IDD) is the main cause of low back pain, and nucleus pulposus (NP) cell apoptosis is an important risk factor of IDD. However, the molecular mechanism of this disease remains unknown.



To assess the potential protective effect of CDDO-ethyl amide (EA) against high-glucose-induced oxidative stress injury in NP cells and to investigate the mechanism of antioxidative effects and apoptotic inhibition.



To find new molecule to inhibit intervertebral disc degeneration.



Viability, reactive oxygen species (ROS) levels, and apoptosis were examined in NP cells. The protein expression levels of HO-1 and Nrf2 were measured through Western blot RESULTS: CDDO-EA elicited cytoprotective effects against NP cell apoptosis and ROS accumulation induced by high glucose. CDDO-EA treatment increased the HO-1 and Nrf2 expression abrogated by HO-1, Nrf2, and mitogen-activated protein kinase inhibitors.



The phosphorylation and nuclear translocation of Nrf2 are crucial for HO-1 overexpression induced by CDDO-EA, which is essential for the cytoprotection against high-glucose-induced oxidative stress in NP cells.
Qingdao Spine Center, Qingdao Municipal Hospital, Qingdao University, 5# Donghai Rd, Shinan District, Qingdao 266061, China.
Cun-Xin
CX
Zhang
Department of Spine Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province 266000, China.
Ting
T
Wang
Department of Spine Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province 266000, China.
Jin-Feng
JF
Ma
Department of Orthopaedics, Zhucheng People's Hospital, Zhucheng 262200, China.
Yang
Y
Liu
Department of Spine and Joint Surgery, Chengyang People's Hospital, Qingdao 266108, China.
Zheng-Gang
ZG
Zhou
Qingdao Spine Center, Qingdao Municipal Hospital, Qingdao University, 5# Donghai Rd, Shinan District, Qingdao 266061, China. Electronic address: dechun-w@163.com.
De-Chun
DC
Wang
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D002478:Cells, Cultured; D019610:Cytoprotection; D005947:Glucose / Q000633:toxicity; D051547:Heme Oxygenase-1 / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D000070614:Nucleus Pulposus / Q000187:drug effects* / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism
C518860:2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid ethyl amide; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D009828:Oleanolic Acid; D051547:Heme Oxygenase-1; D005947:Glucose
Apoptosis; CDDO-EA; Disc degeneration; HO-1; MAPK; Nrf2; Nucleus pulposus cells