Otilonium and pinaverium trigger mitochondrial-mediated apoptosis in rat embryo cortical neurons in vitro

García-Alvarado, Fernanda; Govoni, Giulia; Pascual, Ricardo de; Ruiz-Ruiz, Cristina; Muñoz-Montero, Alicia; Gandı́a, Luis; Diego, Antonio M. G. de; Garcı́a, Antonio G.

doi:10.1016/j.neuro.2018.11.003

Cited by 8 publications

(4 citation statements)

References 40 publications

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“…Nevertheless, some deviation from this model should be considered. Indeed, different reports have shown that in several experimental models, different stimuli that increase intracellular ROS elicit markers of intrinsic apoptotic pathways that can be inhibited by CsA, including mitochondrial proapoptotic protein release, phosphatidylserine exposure, and DNA fragmentation [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]. This suggests that, at least under selected experimental conditions, submaximal MPT might represent an alternative path for apoptosis activation.…”

Section: Involvement Of Mpt In Rcd Subroutinesmentioning

confidence: 99%

Physiopathology of the Permeability Transition Pore: Molecular Mechanisms in Human Pathology

et al. 2020

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Mitochondrial permeability transition (MPT) is the sudden loss in the permeability of the inner mitochondrial membrane (IMM) to low-molecular-weight solutes. Due to osmotic forces, MPT is paralleled by a massive influx of water into the mitochondrial matrix, eventually leading to the structural collapse of the organelle. Thus, MPT can initiate outer-mitochondrial-membrane permeabilization (MOMP), promoting the activation of the apoptotic caspase cascade and caspase-independent cell-death mechanisms. The induction of MPT is mostly dependent on mitochondrial reactive oxygen species (ROS) and Ca2+, but is also dependent on the metabolic stage of the affected cell and signaling events. Therefore, since its discovery in the late 1970s, the role of MPT in human pathology has been heavily investigated. Here, we summarize the most significant findings corroborating a role for MPT in the etiology of a spectrum of human diseases, including diseases characterized by acute or chronic loss of adult cells and those characterized by neoplastic initiation.

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Section: Involvement Of Mpt In Rcd Subroutinesmentioning

confidence: 99%

Physiopathology of the Permeability Transition Pore: Molecular Mechanisms in Human Pathology

et al. 2020

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“…Second, the proposed approach can introduce the novel applications of some drugs. For example, Pinaverium which is a first-line option for curing bowl dysfunctionality, operates as an inhibitor and antagonist of the voltage-dependent calcium channel protein [59]. Moreover, more than 60 countries are exploiting Pinaverium to treat gastrointestinal disorders.…”

Section: Discussionmentioning

confidence: 99%

Synthetic repurposing of drugs against hypertension: a datamining method based on association rules and a novel discrete algorithm

Masoudi-Sobhanzadeh

Masoudi‐Nejad

2020

BMC Bioinformatics

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Background: Drug repurposing aims to detect the new therapeutic benefits of the existing drugs and reduce the spent time and cost of the drug development projects. The synthetic repurposing of drugs may prove to be more useful than the single repurposing in terms of reducing toxicity and enhancing efficacy. However, the researchers have not given it serious consideration. To address the issue, a novel datamining method is introduced and applied to repositioning of drugs for hypertension (HT) which is a serious medical condition and needs some improved treatment plans to help treat it. Results: A novel two-step data mining method, which is based on the If-Then association rules as well as a novel discrete optimization algorithm, was introduced and applied to the synthetic repurposing of drugs for HT. The required data were also extracted from DrugBank, KEGG, and DrugR+ databases. The findings indicated that based on the different statistical criteria, the proposed method outperformed the other state-of-the-art approaches. In contrast to the previously proposed methods which had failed to discover a list on some datasets, our method could find a combination list for all of them. Conclusion: Since the proposed synthetic method uses medications in small dosages, it might revive some failed drug development projects and put forward a suitable plan for treating different diseases such as COVID-19 and HT. It is also worth noting that applying efficient computational methods helps to produce better results.

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“…Second, the proposed approach can introduce novel applications of some drugs. For instance, Pinaverium is a first-line option for curing bowl dysfunctionality and operates as an inhibitor and antagonist of the voltage-dependent calcium channel protein [57]. Moreover, Pinaverium used to be exploited in more than 60 countries and especially applied to cure gastrointestinal disorders.…”

Section: -Discussionmentioning

confidence: 99%

Synthetic Repurposing of Drugs in Hypertension: a Datamining Method Based on Association Rules and a Novel Discrete Algorithm

Masoudi-Sobhanzadeh

Masoudi‐Nejad²

2020

Preprint

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Background Drug repurposing aims to detect the new benefits of the existing drugs and to reduce the spent time and cost of the drug development projects. Although synthetic repurposing of drugs may be more useful than single repurposing in terms of reducing toxicity and enhancing efficacy, the researchers have not taken it into account. To address the issue, a novel datamining method is introduced and applied to the repositioning of drugs in hypertension (HT), which is a serious medical condition and therefore needs to be dealt with effectively through making some improved treatment plans to help cure it. Results a novel two-step data mining method, which is based on the If-Then association rules and a novel discrete optimization algorithm, is proposed and applied to the synthetic repurposing of drugs in HT. The required data are extracted from DruhBank, KEGG, and DrugR+ databases. The outcomes presented that the proposed method outperforms the other state-of-the-art approaches in terms of different statistical criteria. In contrast to the previously proposed methods which failed to discover a list for some datasets, our method managed to suggest a combination of drugs for all the datasets. Conclusion The proposed synthetic method may revive some failed drug development projects and be a suitable plan for curing orphan and rare diseases due to using a low dosage of medicines. It is also essential to use some efficient computational methods to produce better results.

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Otilonium and pinaverium trigger mitochondrial-mediated apoptosis in rat embryo cortical neurons in vitro

Cited by 8 publications

References 40 publications

Physiopathology of the Permeability Transition Pore: Molecular Mechanisms in Human Pathology

Physiopathology of the Permeability Transition Pore: Molecular Mechanisms in Human Pathology

Synthetic repurposing of drugs against hypertension: a datamining method based on association rules and a novel discrete algorithm

Synthetic Repurposing of Drugs in Hypertension: a Datamining Method Based on Association Rules and a Novel Discrete Algorithm

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