Metal Ruthenium Complexes Treat Spinal Cord Injury By Alleviating Oxidative Stress Through Interaction With Antioxidant 1 Copper Chaperone Protein

Advanced Science, 2024 · DOI: 10.1002/advs.202407225 · Published: October 16, 2024

Spinal Cord Injury Pharmacology Neurology

Simple Explanation

Spinal cord injury (SCI) often leads to oxidative stress, which worsens the prognosis. This study explores the potential of ruthenium metal complexes to treat SCI by reducing reactive oxygen species (ROS) through a protein-regulated mechanism, thereby alleviating oxidative stress. Two novel ruthenium (II) complexes were designed, featuring ﬂuorine-based imino-pyridyl ligands. The complexes, named Ru-EA and Ru-PA, demonstrated the ability to protect neurons by scavenging ROS, with Ru-EA showing significantly enhanced ROS scavenging ability and neuroprotective effects compared to Ru-PA. Molecular dynamics simulations suggest that the ruthenium metal complex Ru-EA increases Antioxidant 1 Copper Chaperone protein (ATOX1) expression, reduces oxidative stress, and protects neurons during SCI treatment. Furthermore, Ru-EA improved electrical signals and motor functions in mice with SCI, suggesting a new therapeutic approach for SCI treatment.

Study Duration

Not specified

Participants

Mice with induced spinal cord injury

Evidence Level

Not specified

Key Findings

1
Replacing the 𝜂6-Arene in bz-PA with bz-EA dramatically boosts the ROS neutralizing ability and neuroprotective eﬃcacy of the complexes.
2
The ruthenium complex bz-EA stimulates ATOX1 production, which counters oxidative stress and protects neurons in SCI scenarios.
3
Ruthenium metal complex Ru-EA preserved neurons and encouraged their regrowth, which improved electrical conduction and motor capabilities in spinal cord-injured mice.

Research Summary

This study introduces two novel ruthenium (II) half-sandwich complexes with diverse NˆN-chelating ligands for treating spinal cord injury (SCI). The complex Ru-EA demonstrates superior ROS scavenging ability and neuroprotective efficacy compared to Ru-PA, primarily through stimulating ATOX1 production, which counters oxidative stress. In vivo experiments show that Ru-EA alleviates oxidative stress and inflammation, promotes motor function recovery, and enhances spinal cord signaling in SCI mice, suggesting a potential therapeutic strategy for SCI treatment.

Practical Implications

Novel Therapeutic Strategy

Ruthenium metal complexes, particularly Ru-EA, offer a new therapeutic avenue for treating spinal cord injury by targeting oxidative stress and promoting neuronal regeneration.

ATOX1 as a Key Target

The identification of ATOX1 as a primary protein target for Ru-EA provides insights into the mechanisms of neuroprotection and suggests further research into ATOX1-related therapies.

Improved Motor Function Recovery

The study demonstrates that Ru-EA treatment significantly improves motor function recovery in SCI mice, indicating its potential for enhancing patient outcomes and quality of life.

Study Limitations

1
The study primarily focuses on early-stage effects of Ru-EA on SCI, and long-term outcomes require further investigation.
2
The experiments were conducted on mice, and translation to human clinical trials needs careful consideration.
3
The precise mechanisms of Ru-EA action, beyond ATOX1 upregulation, warrant further exploration.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury