Iridium metal complex targeting oxidation resistance 1 protein attenuates spinal cord injury by inhibiting oxidative stress-associated reactive oxygen species

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-nitro-phenyl)-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 pi 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.