Zafirlukast and vincamine ameliorate tamoxifen-induced oxidative stress and inflammation: Role of the JNK/ERK pathway

El-Dessouki, Ahmed M.; Fattah, Mai A. El; Awad, Azza S.; Zaki, Hala F.

doi:10.1016/j.lfs.2018.04.002

Cited by 25 publications

(15 citation statements)

References 56 publications

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“…S1), therefore reducing the activity of the proapoptotic JNK pathway as well as increasing viability of DJ-1- deficient cells. In agreement with our results, it was demonstrated that VIN exerted a protective effect in rat livers treated with tamoxifen, a compound that induces cell death (El-Dessouki et al, 2018). Indeed, treatment of rats with VIN ameliorated tamoxifen induced hepatic cell injury via suppressing OS and reducing JNK phosphorylation (El-Dessouki et al, 2018).…”

Section: Resultssupporting

confidence: 92%

Disease-modifying effects of Vincamine supplementation inDrosophilaand human cell models of Parkinson’s disease

Sanz

Solana-Manrique

Paricio

2022

Preprint

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Parkinson's disease (PD) is an incurable neurodegenerative disorder caused by the selective loss of dopaminergic neurons in thesubstantia nigra pars compacta. Current therapies are only symptomatic, and are not able to stop or delay its progression. In order to search new and more effective therapies, our group carried out a high-throughput screening assay, identifying several candidate compounds able to suppress motor defects inDJ-1βmutant flies (aDrosophilamodel of familial PD) and to reduce oxidative stress (OS)-induced lethality inDJ-1-deficient SH-SY5Y human cells. One of them was vincamine (VIN), a natural alkaloid obtained from the leaves of Vinca minor. Our results showed that VIN is able to suppress PD-related phenotypes in bothDrosophilaand human cell PD models. Specifically, VIN reduced OS levels in PD model flies. Besides, VIN diminished OS-induced lethality by decreasing apoptosis, increased mitochondrial viability and reduced OS levels inDJ-1-deficient human cells. In addition, we have demonstrated that VIN is able to exert its beneficial role, at least partially, by the inhibition of voltage-gated Na+channels. Therefore, we propose that these channels might be a promising target in the search for new compounds to treat PD, and that VIN constitutes a potential therapeutic treatment for the disease.

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Section: Resultssupporting

confidence: 92%

Disease-modifying effects of Vincamine supplementation inDrosophilaand human cell models of Parkinson’s disease

Sanz

Solana-Manrique

Paricio

2022

Preprint

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“…Zafirlukast is a medication used in the management and treatment of chronic asthma [ 26 ]. Zafirlukast has also been reported to prevent tamoxifen-induced oxidative stress and inflammation [ 27 ] and TNF-αinduced endothelial inflammation [ 28 ]; Bromocriptine has been reported to be used for glycemic control in patients with type 2 diabetes mellitus [ 29 ]. Bromocriptine has also been studied for therapeutic applications in endocrine and neurological diseases [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of NLRP3 and Golph3 ameliorates diabetes-induced neuroinflammation in vitro and in vivo

Zhang

Long

et al. 2022

Aging

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Golgi stress has been observed in various neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Whether Golgi stress participates in hyperglycemia-induced neuroinflammation, and how it is regulated remain unclear. First, we found that high glucose (HG) could induce dispersed Golgi apparatus (GA) in BV2 cells, which can be reversed by knockout of NLRP3. Next, we discovered that HG could promote the interaction of NLRP3 and VPS35 and then enhances the interaction of VPS35 and Golph3; knockout of NLRP3 suppressed the expression of VPS35 and Golph3; knockout of VPS35 reduced the expression of Golph3 but not NLRP3, indicating that HG induced the activation of NLRP3/VPS35/Golph3 pathway in BV2 cells. Further, we elucidated the signaling pathway that Golph3 mediated GA stress in HG condition. We used GST-pulldown and Co-IP experiments methods to show that HG promoted the interaction of Golph3 and Vimentin, knockout of Golph3 alleviated the expression of Vimentin. Knockout out of Golph3 and Vimentin both ameliorated HG induced dispersed Golgi apparatus. Collectively, our study demonstrated that HG regulates GA stress through NLRP3/VPS35/Golph3/Vimentin pathway. At last, we found that a combination of small molecular inhibitors targeting NLRP3 and Golph3 selected by molecular docking could alleviate HG-induced neuroinflammation in vitro and in vivo. Therefore, the molecular inhibitors targeting NLRP3 and Golph3 have great potential for use in the development of anti-diabetes neuroinflammatory therapies.

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“…The data obtained show that the protein levels of pERK and pJNK induced by VLP are signi cantly reduced after RUT treatment. In a previous study, it was reported that signi cant protection against tissue damage was provided by interrupting the ERK/JNK pathway activated by tamoxifen [56].…”

Section: Discussionmentioning

confidence: 99%

Rutin Protects from Destruction by Interrupting the Pathways Playing a Role in the Possible Damage Mechanism of Sodium Valproate in the Liver and Kidney Tissues of Rats

Kandemir

İleritürk

Gür

2021

Preprint

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Background: The present study investigated the effects of rutin (RUT), which has various biological and pharmacological properties, on liver and kidney damage caused by histone deacetylase inhibitor valproic acid (VLP), which is used in the treatment of many psychiatric disorders.Methods and Results: In the study, 50 or 100 mg/kg RUT treatment was administered 30 minutes after 500 mg/kg VLP was given to rats for 14 days. Then, some pathways that may be involved in the damage mechanism of VLP in liver and kidney tissues were investigated using biochemical, RT-PCR and Western blotting techniques. The results show that the levels of MDA induced by VLP in liver and kidney tissues decreased after RUT treatment, and the levels of SOD, CAT, GPx and GSH suppressed by VLP increased after RUT administration. It was observed that ER stress induced by oxidative stress was alleviated by suppressing the expressions of ATF-6, PERK, IRE1 and GRP78 after RUT treatment. It was observed that the expressions of NF-kB, TNF-a, IL-6, JAK2 and STAT3 in the inflammatory pathway increased after VLP administration, while RUT treatment decreased the levels of these markers. It is also among the data obtained that the levels of markers that play a role in the regulation of apoptosis (Bax, Bcl-2, kaspaz-3, pERK, pJNK) or autophagy (Beclin-1, LC3A, LC3B) approach the control group after RUT treatment.Conclusions: Taken together, it was determined that RUT treatment protected against liver and kidney damage by attenuating VLP-induced oxidative stress, ER stress, inflammation, apoptosis and autophagy.

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Zafirlukast and vincamine ameliorate tamoxifen-induced oxidative stress and inflammation: Role of the JNK/ERK pathway

Cited by 25 publications

References 56 publications

Disease-modifying effects of Vincamine supplementation inDrosophilaand human cell models of Parkinson’s disease

Disease-modifying effects of Vincamine supplementation inDrosophilaand human cell models of Parkinson’s disease

Inhibition of NLRP3 and Golph3 ameliorates diabetes-induced neuroinflammation in vitro and in vivo

Rutin Protects from Destruction by Interrupting the Pathways Playing a Role in the Possible Damage Mechanism of Sodium Valproate in the Liver and Kidney Tissues of Rats

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