Metal Ruthenium Complexes Treat Spinal Cord Injury By Alleviating Oxidative Stress Through Interaction With Antioxidant 1 Copper Chaperone Protein
Abstract Oxidative stress is a major factor affecting spinal cord injury (SCI) prognosis. A ruthenium metal complex can aid in treating SCI by scavenging reactive oxygen species via a protein‐regulated mechanism to alleviate oxidative stress. This study aimed to introduce a pioneering strategy for S...
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| Format: | Article |
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Wiley
2024-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202407225 |
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| author | Juanjuan Li Cheng Peng Caiqiang Huang Li Wan Ke Wang Ping Wu Tianjun Chen Guodong Sun Rui Guo Hongsheng Lin Zhisheng Ji |
| author_facet | Juanjuan Li Cheng Peng Caiqiang Huang Li Wan Ke Wang Ping Wu Tianjun Chen Guodong Sun Rui Guo Hongsheng Lin Zhisheng Ji |
| author_sort | Juanjuan Li |
| collection | DOAJ |
| description | Abstract Oxidative stress is a major factor affecting spinal cord injury (SCI) prognosis. A ruthenium metal complex can aid in treating SCI by scavenging reactive oxygen species via a protein‐regulated mechanism to alleviate oxidative stress. This study aimed to introduce a pioneering strategy for SCI treatment by designing two novel half‐sandwich ruthenium (II) complexes containing diverse N^N‐chelating ligands. The general formula is [(η6‐Arene)Ru(N^N)Cl]PF6, where arene is either 2‐phenylethanol‐1‐ol (bz‐EA) or 3‐phenylpropanol‐1‐ol (bz‐PA), and the N^N‐chelating ligands are fluorine‐based imino‐pyridyl ligands. This study shows that these ruthenium metal complexes protect neurons by scavenging reactive oxygen species. Notably, η6‐Arene substitution from bz‐PA to bz‐EA significantly enhances reactive oxygen species scavenging ability and neuroprotective effect. Additionally, molecular dynamics simulations indicate that the ruthenium metal complex increases Antioxidant 1 Copper Chaperone protein expression, reduces oxidative stress, and protects neurons during SCI treatment. Furthermore, ruthenium metal complex protected spinal cord neurons and stimulated their regeneration, which improves electrical signals and motor functions in mice with SCI. Thus, this treatment strategy using ruthenium metal complexes can be a new therapeutic approach for the efficient treatment of SCI. |
| format | Article |
| id | doaj-art-e78129258f03434fa13b84f59ec77181 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-e78129258f03434fa13b84f59ec771812025-08-20T02:19:01ZengWileyAdvanced Science2198-38442024-12-011145n/an/a10.1002/advs.202407225Metal Ruthenium Complexes Treat Spinal Cord Injury By Alleviating Oxidative Stress Through Interaction With Antioxidant 1 Copper Chaperone ProteinJuanjuan Li0Cheng Peng1Caiqiang Huang2Li Wan3Ke Wang4Ping Wu5Tianjun Chen6Guodong Sun7Rui Guo8Hongsheng Lin9Zhisheng Ji10Department of Orthopedics The First Affiliated Hospital Jinan University Guangzhou Guangdong 510632 ChinaDepartment of Orthopedics The First Affiliated Hospital Jinan University Guangzhou Guangdong 510632 ChinaDepartment of Orthopedics The First Affiliated Hospital Jinan University Guangzhou Guangdong 510632 ChinaDepartment of Orthopedics The First Affiliated Hospital Jinan University Guangzhou Guangdong 510632 ChinaDepartment of Orthopedics The First Affiliated Hospital Jinan University Guangzhou Guangdong 510632 ChinaDepartment of Orthopedics The First Affiliated Hospital Jinan University Guangzhou Guangdong 510632 ChinaDepartment of Orthopedics The First Affiliated Hospital Jinan University Guangzhou Guangdong 510632 ChinaDepartment of Orthopedics The First Affiliated Hospital Jinan University Guangzhou Guangdong 510632 ChinaKey Laboratory of Biomaterials of Guangdong Higher Education Institutes Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development Department of Biomedical Engineering Jinan University Guangzhou 510632 ChinaDepartment of Orthopedics The First Affiliated Hospital Jinan University Guangzhou Guangdong 510632 ChinaDepartment of Orthopedics The First Affiliated Hospital Jinan University Guangzhou Guangdong 510632 ChinaAbstract Oxidative stress is a major factor affecting spinal cord injury (SCI) prognosis. A ruthenium metal complex can aid in treating SCI by scavenging reactive oxygen species via a protein‐regulated mechanism to alleviate oxidative stress. This study aimed to introduce a pioneering strategy for SCI treatment by designing two novel half‐sandwich ruthenium (II) complexes containing diverse N^N‐chelating ligands. The general formula is [(η6‐Arene)Ru(N^N)Cl]PF6, where arene is either 2‐phenylethanol‐1‐ol (bz‐EA) or 3‐phenylpropanol‐1‐ol (bz‐PA), and the N^N‐chelating ligands are fluorine‐based imino‐pyridyl ligands. This study shows that these ruthenium metal complexes protect neurons by scavenging reactive oxygen species. Notably, η6‐Arene substitution from bz‐PA to bz‐EA significantly enhances reactive oxygen species scavenging ability and neuroprotective effect. Additionally, molecular dynamics simulations indicate that the ruthenium metal complex increases Antioxidant 1 Copper Chaperone protein expression, reduces oxidative stress, and protects neurons during SCI treatment. Furthermore, ruthenium metal complex protected spinal cord neurons and stimulated their regeneration, which improves electrical signals and motor functions in mice with SCI. Thus, this treatment strategy using ruthenium metal complexes can be a new therapeutic approach for the efficient treatment of SCI.https://doi.org/10.1002/advs.202407225antioxidant 1 copper chaperonereactive oxygen speciesruthenium metal complexesspinal cord injury |
| spellingShingle | Juanjuan Li Cheng Peng Caiqiang Huang Li Wan Ke Wang Ping Wu Tianjun Chen Guodong Sun Rui Guo Hongsheng Lin Zhisheng Ji Metal Ruthenium Complexes Treat Spinal Cord Injury By Alleviating Oxidative Stress Through Interaction With Antioxidant 1 Copper Chaperone Protein Advanced Science antioxidant 1 copper chaperone reactive oxygen species ruthenium metal complexes spinal cord injury |
| title | Metal Ruthenium Complexes Treat Spinal Cord Injury By Alleviating Oxidative Stress Through Interaction With Antioxidant 1 Copper Chaperone Protein |
| title_full | Metal Ruthenium Complexes Treat Spinal Cord Injury By Alleviating Oxidative Stress Through Interaction With Antioxidant 1 Copper Chaperone Protein |
| title_fullStr | Metal Ruthenium Complexes Treat Spinal Cord Injury By Alleviating Oxidative Stress Through Interaction With Antioxidant 1 Copper Chaperone Protein |
| title_full_unstemmed | Metal Ruthenium Complexes Treat Spinal Cord Injury By Alleviating Oxidative Stress Through Interaction With Antioxidant 1 Copper Chaperone Protein |
| title_short | Metal Ruthenium Complexes Treat Spinal Cord Injury By Alleviating Oxidative Stress Through Interaction With Antioxidant 1 Copper Chaperone Protein |
| title_sort | metal ruthenium complexes treat spinal cord injury by alleviating oxidative stress through interaction with antioxidant 1 copper chaperone protein |
| topic | antioxidant 1 copper chaperone reactive oxygen species ruthenium metal complexes spinal cord injury |
| url | https://doi.org/10.1002/advs.202407225 |
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