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

ABSTRACT: 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, (Cp^xbiPh) Ir (N^N) Cl, where Cp^xbiPh 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.

SUBMITTER: Peng C

PROVIDER: S-EPMC10587759 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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

Peng Cheng C Luo Jianxian J Wang Ke K Li Jianping J Ma Yanming Y Li Juanjuan J Yang Hua H Chen Tianjun T Zhang Guowei G Ji Xin X Liao Yuhui Y Lin Hongsheng H Ji Zhisheng Z

Redox biology 20231010

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, (Cp<sup>xbiPh</sup>) Ir (N^N) Cl, where Cp<sup>xbiPh</sup> 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 antioxi ...[more]

PMID: 37857001

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Project description:BackgroundThe permeability of the blood-spinal cord barrier (BSCB) is mainly determined by junction complexes between adjacent endothelial cells (ECs), including tight junctions (TJs) and adherens junctions (AJs), which can be severely damaged after spinal cord injury (SCI). Exercise training is a recognized method for the treatment of SCI. The destruction of the BSCB mediated by matrix metalloproteinases (MMPs) leads to inflammation, neurotoxin production, and neuronal apoptosis. The failure of new blood vessels to effectively regenerate is also an important cause of delayed recovery after SCI. For the first time, we introduced water treadmill training (TT) to help SCI rats successfully exercise and measured the effects of TT in promoting recovery after SCI and the possible mechanisms involved.MethodsSprague-Dawley (200-250 g) rats were randomly divided into the following three groups: sham operated, SCI, and SCI + TT. Animals were sacrificed at 7 or 14 days post-surgery. The degree of neurological deficit, tissue morphology and BSCB permeability were assessed by the Basso-Beattie-Bresnahan (BBB) motor function scale and appropriate staining protocols, and apoptosis, protein expression and vascular EC ultrastructure were assessed by TUNEL staining, Western blotting, immunofluorescence and transmission electron microscopy (TEM).ResultsOur experiments showed that TT reduced permeability of the BSCB and decreased structural tissue damage. TT significantly improved functional recovery when compared with that in the SCI group; TJ and AJ proteins expression increased significantly after TT, and training reduced apoptosis induced by SCI. TT could promote angiogenesis, and MMP-2 and MMP-9 expression was significantly inhibited by TT.ConclusionsThe results of this study indicate that TT promotes functional recovery for the following reasons: TT (1) protects residual BSCB structure from further damage, (2) promotes vascular regeneration, and (3) inhibits MMP-2/9 expression to mitigate BSCB damage.

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

Publications

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

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