TXNIP knockdown protects rats against bupivacaine-induced spinal neurotoxicity via the inhibition of oxidative stress and apoptosis

Zhao, Yang; Chen, Yuanyuan; Liu, Ziru; Zhou, Lei; Huang, Jiao; Luo, Xi; Luo, Yunpeng; Li, Jia; Lin, Yunan; Lai, Jian; Liu, Jingchen

doi:10.1016/j.freeradbiomed.2024.04.223

Cited by 3 publications

(1 citation statement)

References 75 publications

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“…The BCL-2 protein family plays a pivotal role in the mitochondria-mediated apoptotic pathway [35]. BCL-2 plays a pivotal role in promoting cellular survival by exerting its anti-apoptotic efficacy, while Bax counteracts the effect of BCL-2 and promotes apoptosis [36]. Bax can also translocate to the mitochondrial membrane and promote the release of Cyto-C [37].…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Flavonoids and Metformin on Protection of the Methylglyoxal-Induced Damage in PC-12 Neuroblastoma Cells: Structure–Activity Relationship and Potential Target

Zhang,

He,

Wang

et al. 2024

Molecules

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Methylglyoxal-induced ROS elevation is the primary cause of neuronal damage. Metformin is a traditional hypoglycemic drug that has been reported to be beneficial to the nervous system. In this study, flavonoids were found to enhance the protective effect of metformin when added at a molar concentration of 0.5%. The structure–activity relationship (SAR) analysis indicated that ortho- substitution in the B ring, and the absence of double bonds between the 2 and 3 position combined with the gallate substitution with R configuration at the 3 position in the C ring played crucial roles in the synergistic effects, which could be beneficial for designing a combination of the compounds. Additionally, the mechanism study revealed that a typical flavonoid, EGCG, enhanced ROS scavenging and anti-apoptotic ability via the BCL2/Bax/Cyto C/Caspase-3 pathway, and synergistically inhibited the expression of GSK-3β, BACE-1, and APP in PC-12 cells when used in combination with metformin. The dose of metformin used in the combination was only 1/4 of the conventional dose when used alone. These results suggested that ROS-mediated apoptosis and the pathways related to amyloid plaques (Aβ) formation can be the targets for the synergistic neuroprotective effects of flavonoids and metformin.

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Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Flavonoids and Metformin on Protection of the Methylglyoxal-Induced Damage in PC-12 Neuroblastoma Cells: Structure–Activity Relationship and Potential Target

Zhang,

He,

Wang

et al. 2024

Molecules

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Design, Synthesis and Biological Evaluation of Galantamine Analogues for Cognitive Improvement in Alzheimer's Disease

Li,

Ma,

et al. 2024

European Journal of Medicinal Chemistry

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Copper oxide nanoparticles exacerbate chronic obstructive pulmonary disease by activating the TXNIP-NLRP3 signaling pathway

Kim,

Pak,

Lee

et al. 2024

Part Fibre Toxicol

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Background Although copper oxide nanoparticles (CuONPs) offer certain benefits to humans, they can be toxic to organs and exacerbate underlying diseases upon exposure. Chronic obstructive pulmonary disease (COPD), induced by smoking, can worsen with exposure to various harmful particles. However, the specific impact of CuONPs on COPD and the underlying mechanisms remain unknown. In this study, we investigated the toxic effects of CuONPs on the respiratory tract, the pathophysiology of CuONPs exposure-induced COPD, and the mechanism of CuONPs toxicity, focusing on thioredoxin-interacting protein (TXNIP) signaling using a cigarette smoke condensate (CSC)-induced COPD model. Results In the toxicity study, CuONPs exposure induced an inflammatory response in the respiratory tract, including inflammatory cell infiltration, cytokine production, and mucus secretion, which were accompanied by increased TXNIP, NOD-like receptor protein 3 (NLRP3), caspase-1, and interleukin (IL)-1β. In the COPD model, CuONPs exposure induced the elevation of various indexes related to COPD, as well as increased TXNIP expression. Additionally, TNXIP-knockout (KO) mice showed a significantly decreased expression of NLRP3, caspase-1, and IL-1β and inflammatory responses in CuONPs-exposed COPD mice. These results were consistent with the results of an in vitro experiment using H292 cells. By contrast, TNXIP-overexpressed mice had a markedly increased expression of NLRP3, caspase-1, and IL-1β and inflammatory responses in CuONPs-exposed COPD mice. Conclusions We elucidated the exacerbating effect of CuONPs exposure on the respiratory tract with underlying COPD, as well as related signaling transduction via TXNIP regulation. CuONPs exposure significantly increased inflammatory responses in the respiratory tract, which was correlated with elevated TXNIP-NLRP3 signaling. Supplementary Information The online version contains supplementary material available at 10.1186/s12989-024-00608-3.

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TXNIP knockdown protects rats against bupivacaine-induced spinal neurotoxicity via the inhibition of oxidative stress and apoptosis

Cited by 3 publications

References 75 publications

Synergistic Effect of Flavonoids and Metformin on Protection of the Methylglyoxal-Induced Damage in PC-12 Neuroblastoma Cells: Structure–Activity Relationship and Potential Target

Synergistic Effect of Flavonoids and Metformin on Protection of the Methylglyoxal-Induced Damage in PC-12 Neuroblastoma Cells: Structure–Activity Relationship and Potential Target

Design, Synthesis and Biological Evaluation of Galantamine Analogues for Cognitive Improvement in Alzheimer's Disease

Copper oxide nanoparticles exacerbate chronic obstructive pulmonary disease by activating the TXNIP-NLRP3 signaling pathway

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