Iridium metal complex targeting oxidation resistance 1 protein attenuates spinal cord injury by inhibiting oxidative stress-associated reactive oxygen species
Cheng Peng,
Jianxian Luo,
Ke Wang,
Jianping Li,
Yanming Ma,
Juanjuan Li,
Hua Yang,
Tianjun Chen,
Guowei Zhang,
Xin Ji,
Yuhui Liao,
Hongsheng Lin,
Zhisheng Ji
Affiliations
Cheng Peng
Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510632, China
Jianxian Luo
Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510632, China
Ke Wang
Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510632, China
Jianping Li
Department of Anatomy, Shaoyang University Puai Medical College, Shaoyang, Hunan, 422099, China
Yanming Ma
Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510632, China
Juanjuan Li
Guangdong Key Laboratory of Urology and Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
Hua Yang
Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510632, China
Tianjun Chen
Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510632, China
Guowei Zhang
Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510632, China
Xin Ji
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Engineering Technology Research Center of Drug Carrier of Guangdong, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China; Corresponding author.
Yuhui Liao
Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou, 510091, China; Corresponding author.
Hongsheng Lin
Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510632, China; Corresponding author.
Zhisheng Ji
Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510632, China; Corresponding author.
Oxidative stress is a key factor leading to profound neurological deficits following spinal cord injury (SCI). In this study, we present the development and potential application of an iridium (iii) complex, (CpxbiPh) Ir (N^N) Cl, where CpxbiPh represents 1-biphenyl-2,3,4,5-tetramethyl cyclopentadienyl, and N^N denotes 2-(3-(4-nitrophenyl)-1H-1,2,4-triazol-5-yl) pyridine chelating agents, to address this challenge through a mechanism governed by the regulation of an antioxidant protein. This iridium complex, IrPHtz, can modulate the Oxidation Resistance 1 (OXR1) protein levels within spinal cord tissues, thus showcasing its antioxidative potential. By eliminating reactive oxygen species (ROS) and preventing apoptosis, the IrPHtz demonstrated neuroprotective and neural healing characteristics on injured neurons. Our molecular docking analysis unveiled the presence of π stacking within the IrPHtz-OXR1 complex, an interaction that enhanced OXR1 expression, subsequently diminishing oxidative stress, thwarting neuroinflammation, and averting neuronal apoptosis. Furthermore, in in vivo experimentation with SCI-afflicted mice, IrPHtz was efficacious in shielding spinal cord neurons, promoting their regrowth, restoring electrical signaling, and improving motor performance. Collectively, these findings underscore the potential of employing the iridium metal complex in a novel, protein-regulated antioxidant strategy, presenting a promising avenue for therapeutic intervention in SCI.
