Contrasting Role of Concentration in Rivaroxaban Induced Toxicity and Oxidative Stress in Isolated Kidney Mitochondria

Samiei, Fatemeh; Sajjadi, Hanieh; Jamshidzadeh, Akram; Seydi, Enayatollah; Pourahmad, Jalal

doi:10.1055/a-1001-2154

Cited by 12 publications

(11 citation statements)

References 31 publications

(58 reference statements)

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“…Each sample was measured using a fluorimeter set at 490 nm excitation and 520 nm emission wavelengths. The results were reported as %ΔΨm (the percentage of MMP) [24]. In this test, cumene hydroperoxide (a potent oxidizing agent EC50 = 120 µM [19]) was used as a negative control was used as a negative control 30 min after sofosbuvir (400 µM) addition.…”

Section: Investigation Of the Mitochondrial Membrane Potential (Mmp)mentioning

confidence: 99%

Contrasting Role of Dose Increase in Modulating Sofosbuvir-Induced Hepatocyte Toxicity

2020

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Sofosbuvir, the oral direct-acting antiviral, is a medication, which used as the effective treatment for hepatitis C infection. Although sofosbuvir thought to have few adverse-effects, there have been some experiences of serious drug-induced hepatotoxicity. In this research, the molecular/cellular pathways that lead to sofosbuvir-induced hepatotoxicity were evaluated on isolated rat hepatocytes. Rat hepatocytes were isolated using collagenase reperfusion technique. In evaluating the different pathways of sofosbuvir-induced hepatotoxicity, ROS formation, mitochondrial membrane potential collapse, lysosomal membrane damage, glutathione depletion, and the percentage of apoptosis versus necrosis were determined. Our data demonstrated that the cytotoxic effect of sofosbuvir in lower concentrations (25, 50 and 100 µM) is mediated by above stream pathways. On the other hand, sofosbuvir acts in opposite directions at higher concentrations (400 µM) and acts as an antioxidant and hepatoprotective. We concluded that sofosbuvir while looking toxic and pro-oxidant in lower concentrations, acts as protective and antioxidant in higher concentrations.

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Section: Investigation Of the Mitochondrial Membrane Potential (Mmp)mentioning

confidence: 99%

Contrasting Role of Dose Increase in Modulating Sofosbuvir-Induced Hepatocyte Toxicity

2020

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“…4 However, a more recent in vitro study, using rat kidney mitochondria, reported evidence of mitochondrial swelling and a collapse of the membrane potential following exposure to low doses of rivaroxaban. 5 The effect of apixaban, which is structurally related to rivaroxaban, has yet to be investigated on mitochondrial function. 6 Recent research supports not only an association between reduced cerebral mitochondrial function and neuropsychiatric symptoms and disorders, but also the aetiological role it may play.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Treatment with the direct oral anticoagulants (DOACs) apixaban and rivaroxaban associated with significant worsening of behavioural and psychological symptoms of dementia (BPSD)

et al. 2021

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We report the cases of two patients who developed worsening behavioural and psychological symptoms of dementia (BPSD), coinciding with starting the factor Xa inhibitor direct oral anticoagulant medications apixaban and rivaroxaban, respectively. Both patients required detaining under the Mental Health Act. Their symptoms improved significantly, within 2 weeks, on switching to alternative anticoagulant therapies and they were both discharged from the acute psychiatric ward. Front-line staff should partake in postmarketing surveillance of medications, completing the Medicines and Healthcare products Regulatory Agency yellow cards for example (UK). There is increasing evidence for an aetiological role of cerebral mitochondrial dysfunction in neuropsychiatric disorders. Development of a rating scale of drugs that are potentially less toxic to cerebral mitochondria could inform national prescribing guidelines and enable safer treatments to be offered to older people, reducing the likely hood of them experiencing apparent BPSD.

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“…There is evidence that factor Xa has proinflammatory effects, therefore [65]. However, it has recently been shown to have protective effects against oxidative stress and mitochondrial toxicity [66]. Due to their chemical structure, sarilumab and fingolimod could have effects similar to CQ/HCQ in SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

Treatment of coronavirus disease: Implementation of machine learning algorithms for drug screening

MDC¹,

Parada²,

FM³

et al. 2021

J Clin Images Med Case Rep

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Background and objectives: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the emergence of the immediate and urgent need to develop of therapeutic measure capable of reducing its impact on the health of the population and in health and economic resources. Based on the data provided by these bioassays, in this work propose the implementation of machine learning algorithms based on a Quantitative Structure-Activity Relationship (QSAR) model for drug screening of compounds with the potential to inhibit Quinone Reductase 2 (QR2) and to replace the anti-inflammatory function of chloroquine and hydroxychloroquine in the treatment of COVID-19 avoiding its adverse effects. Methods: QSAR modeling was performed to calculate the mathematical correlations between the chemical properties of QR2 inhibitor compounds, from different bioassays, and their biochemical response on QR2 activity. The values of 22 properties were obtained by means of automatic extraction techniques from PubChem’s PUG REST service. The following classification algorithms were applied: Logistic Regression, Random Forest and Multi-Layer Perceptron. To perform the computational screening, 279 drugs were selected and divided into 7 groups: Group I or PubChem-Covid-19, settled for compounds labeled by PubChem as COVID-19 (n=104); Group II, drugs with structure similar to dihydroxyphenylalanine (dopa) (n=110); Group III, ubiquins (n=16); Group IV, used in clinical trials (n=18); Group V, amantadine, pramipexole, dabigatran, rotigotine and naphthoquinone (n=5); Group VI, vitamins B (n=10); and Group VII, vitamins K (n=16). A classification threshold for Active of 0.95 was established. Results: 54 compounds were identified as Actives. Camostat, relacatib, 5-Aminopyrimidine, clovamide, coenzyme Q4, decylubiquinone, sarilumab, fingolimod, rivaroxabán, prosultiamine and alinamin, for its potential use in COVID-19, were the most significant. Conclusions: It was presented a series of compounds identified by the QSAR model as QR2 inhibitors and we analyze the main drugs in that series according to their availability and current use.

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Contrasting Role of Concentration in Rivaroxaban Induced Toxicity and Oxidative Stress in Isolated Kidney Mitochondria

Cited by 12 publications

References 31 publications

Contrasting Role of Dose Increase in Modulating Sofosbuvir-Induced Hepatocyte Toxicity

Contrasting Role of Dose Increase in Modulating Sofosbuvir-Induced Hepatocyte Toxicity

Treatment with the direct oral anticoagulants (DOACs) apixaban and rivaroxaban associated with significant worsening of behavioural and psychological symptoms of dementia (BPSD)

Treatment of coronavirus disease: Implementation of machine learning algorithms for drug screening

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