Dimercaprol is an acrolein scavenger that mitigates acrolein‐mediated <scp>PC</scp>‐12 cells toxicity and reduces acrolein in rat following spinal cord injury

Tian, Rong; Shi, Riyi

doi:10.1111/jnc.14025

Cited by 31 publications

(18 citation statements)

References 55 publications

(167 reference statements)

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“…When treated with NGF, the PC-12 cells stop dividing and terminally differentiate into neuron-like cells. This makes PC-12 cells useful as a model to study the function and pathophysiology of neurons [32], and such a model has been used in SCI research [33]. We therefore thought its use was appropriate for this study.…”

Section: Discussionmentioning

confidence: 99%

The protective effect of microRNA-21 in neurons after spinal cord injury

Zhang

Luo

et al. 2018

Spinal Cord

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Study design Experimental animal study. Objectives To validate the anti-apoptosis effect of microRNA-21 in neurons after spinal cord injury (SCI) and explore the mechanism. Setting Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. Methods In situ hybridization was used to detect the expression of miR-21 in spinal cord neurons (n = 24). In a rat contusion SCI model (n = 48), we upregulated the miR-21 level around the injured area using miR-21 lentiviral vectors and evaluated the therapeutic effect with histology and behavioural scores. In neuronal cells, oxygen-glucose deprivation (OGD) was exerted to imitate SCI, and we explored the biomechanism using molecular biology and a dual-luciferase reporter assay. Results miR-21 was expressed in spinal cord neurons and was found to improve neuronal survival and promote functional recovery in rat SCI models. The in vitro results in PC-12 cells revealed that the augmentation of endogenous miR-21 was able to reduce neuronal cell death after OGD. In addition, overexpression of miR-21 was able to reduce cellular apoptosis via decreasing PDCD4 protein levels, and caspase-3 activity was also influenced. Transfection of miR-21 into 293T cells was able to decrease luciferase activity in a reporter assay system, including the 3′ untranslated region of PDCD4. Conclusions miR-21 may have a protective role in neuronal apoptosis after SCI. PDCD4 may be a functional target gene involved in the miR-21-mediated anti-apoptotic effect through an miR-21/PDCD4/caspase-3 pathway.

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Section: Discussionmentioning

confidence: 99%

The protective effect of microRNA-21 in neurons after spinal cord injury

Zhang

Luo

et al. 2018

Spinal Cord

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“…SCI is a severe neurological disease, and mounting researches have used PC12 cells as important adjuncts and surrogates for studies of SCI in humans [20,21]. Therefore, in this study, we investigated the protective effects of CAP against LPS-induced injuries in PC12 cells and explored its underlying molecular mechanisms.…”

Section: Original Papermentioning

confidence: 99%

Chinese Angelica Polysaccharide (CAP) Alleviates LPS-Induced Inflammation and Apoptosis by Down-Regulating COX-1 in PC12 Cells

Xie

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Chinese angelica polysaccharide (CAP) is the main effective ingredient of angelica sinensis and exerts anti-inflammatory and anti-apoptotic effects on many diseases. This study aimed to explore the pharmacological potential of CAP on spinal cord injury (SCI). Methods: PC12 cells were pretreated by CAP and were subjected to LPS. Transfection was performed to alter the expression of COX-1. Cell viability and apoptotic cell rate were measured by CCK-8 and flow cytometry respectively. qRT-PCR and western blot analysis were performed to assess the expression changes of pro-inflammatory cytokines, apoptosis-related factor and core kinases in PI3K/AKT pathway. Results: LPS stimulation induced significant cell damage in PC12 cells as cell viability was repressed, apoptosis was induced and the expression levels of IL-1β, IL-6, IL-8, and TNF-α were increased. CAP pretreatment protected PC12 cells against LPS-induced cell damage. Meanwhile CAP treatment reduced the expression of COX-1 even in LPS-stimulated PC12 cells. More importantly, COX-1 overexpression abolished the protective effects of CAP on LPS-injured PC12 cells. Finally, Western blot analytical results showed that CAP activated PI3K/AKT pathway also in a COX-1-dependent manner. Conclusion: CAP exerted anti-apoptotic and anti-inflammatory effects on LPS-injured PC12 cells via down-regulation of COX-1.

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“…Marimastat was found to effectively inhibit the hemorrhagic, coagulant and defibrinogenating effects and proteinase activities induced by Echis ocellatus venom [42]. Dimercaprol, a historical drug approved by the World Health Organization (WHO) for treatment of heavy metal poisoning [44], contains two metal-chelating thiol groups and has long been used against arsenic, mercury, gold, lead and antimony intoxication [45][46][47]. It also represents a treatment option for Wilson's disease in which the body retains copper.…”

Section: Introductionmentioning

confidence: 99%

Neutralizing Effects of Small Molecule Inhibitors and Metal Chelators on Coagulopathic Viperinae Snake Venom Toxins

et al. 2020

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Animal-derived antivenoms are the only specific therapies currently available for the treatment of snake envenoming, but these products have a number of limitations associated with their efficacy, safety and affordability for use in tropical snakebite victims. Small molecule drugs and drug candidates are regarded as promising alternatives for filling the critical therapeutic gap between snake envenoming and effective treatment. In this study, by using an advanced analytical technique that combines chromatography, mass spectrometry and bioassaying, we investigated the effect of several small molecule inhibitors that target phospholipase A2 (varespladib) and snake venom metalloproteinase (marimastat, dimercaprol and DMPS) toxin families on inhibiting the activities of coagulopathic toxins found in Viperinae snake venoms. The venoms of Echis carinatus, Echis ocellatus, Daboia russelii and Bitis arietans, which are known for their potent haemotoxicities, were fractionated in high resolution onto 384-well plates using liquid chromatography followed by coagulopathic bioassaying of the obtained fractions. Bioassay activities were correlated to parallel recorded mass spectrometric and proteomics data to assign the venom toxins responsible for coagulopathic activity and assess which of these toxins could be neutralized by the inhibitors under investigation. Our results showed that the phospholipase A2-inhibitor varespladib neutralized the vast majority of anticoagulation activities found across all of the tested snake venoms. Of the snake venom metalloproteinase inhibitors, marimastat demonstrated impressive neutralization of the procoagulation activities detected in all of the tested venoms, whereas dimercaprol and DMPS could only partially neutralize these activities at the doses tested. Our results provide additional support for the concept that combinations of small molecules, particularly the combination of varespladib with marimastat, serve as a drug-repurposing opportunity to develop new broad-spectrum inhibitor-based therapies for snakebite envenoming.

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Dimercaprol is an acrolein scavenger that mitigates acrolein‐mediated PC‐12 cells toxicity and reduces acrolein in rat following spinal cord injury

Cited by 31 publications

References 55 publications

The protective effect of microRNA-21 in neurons after spinal cord injury

The protective effect of microRNA-21 in neurons after spinal cord injury

Chinese Angelica Polysaccharide (CAP) Alleviates LPS-Induced Inflammation and Apoptosis by Down-Regulating COX-1 in PC12 Cells

Neutralizing Effects of Small Molecule Inhibitors and Metal Chelators on Coagulopathic Viperinae Snake Venom Toxins

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