The Potential Use of Metformin, Dipyridamole, N-Acetylcysteine and Statins as Adjunctive Therapy for Systemic Lupus Erythematosus

Tan, Marcus Kai Xuan; Heng, Thurston Yan Jia; Mak, Anselm

doi:10.3390/cells8040323

Cited by 27 publications

(25 citation statements)

References 96 publications

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“…Dipyridamole is an FDA-approved nonspecific PDE inhibitor used for thrombosis and was discovered to inhibit NET formation ( Ali et al, 2019 ). Dipyridamole acts by increasing intracellular cAMP levels and blocking adenosine reuptake in cells, thereby leading to its antiplatelet and vasodilatory effects ( Tan et al, 2019 ). In a trial including 31 COVID-19 patients, dipyridamole showed improvement in severe cases with significantly reduced D-dimer levels ( Liu et al, 2020 ).…”

Section: Drugs Targeting Neutrophils For Covid-19 Associated Ardsmentioning

confidence: 99%

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

et al. 2020

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This review describes targeting neutrophils as a potential therapeutic strategy for acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 (COVID-19), a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutrophil counts are significantly elevated in patients with COVID-19 and significantly correlated with disease severity. The neutrophil-to-lymphocyte ratio can serve as a clinical marker for predicting fatal complications related to ARDS in patients with COVID-19. Neutrophil-associated inflammation plays a critical pathogenic role in ARDS. The effector functions of neutrophils, acting as respiratory burst oxidants, granule proteases, and neutrophil extracellular traps, are linked to the pathogenesis of ARDS. Hence, neutrophils can not only be used as pathogenic markers but also as candidate drug targets for COVID-19 associated ARDS.

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Section: Drugs Targeting Neutrophils For Covid-19 Associated Ardsmentioning

confidence: 99%

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

et al. 2020

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“…In addition, some studies have investigated hydroxychloroquine in association with metformin in diabetic patients to achieve a better control of type-2 diabetes conditions [10]. Conversely, metformin was studied as an adjunctive therapy for systemic lupus erythematous, a condition for which hydroxychloroquine is routinely administered [11]. In fact, our study was prompted by the paper from Rajeshkumar's group [5] showing a higher mortality ratio (30-40%) in mice treated with hydroxychloroquine + metformin in comparison with the control group receiving metformin alone.…”

Section: Discussionmentioning

confidence: 99%

A New Drug–Drug Interaction Between Hydroxychloroquine and Metformin? A Signal Detection Study

Montastruc

Toutain

2020

Drug Saf

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Introduction Hydroxychloroquine was recently promoted in patients infected with COVID-19 infection. A recent experimental study has suggested an increased toxicity of hydroxychloroquine in association with metformin in mice. Objective The present study was undertaken to investigate the reality of this putative drug-drug interaction between hydroxychloroquine and metformin using pharmacovigilance data. Methods Using VigiBase ® , the WHO pharmacovigilance database, we performed a disproportionality analysis (case/noncase study). Cases were reports of fatal outcomes with the drugs of interest and non-cases were all other reports for these drugs registered between 1 January 2000 and 31 December 2019. Data with hydroxychloroquine (or metformin) alone were compared with the association hydroxychloroquine + metformin. Results are reported as ROR (reporting odds ratio) with their 95% confidence interval. Results Of the 10,771 Individual Case Safety Reports (ICSR) involving hydroxychloroquine, 52 were recorded as 'fatal outcomes'. In comparison with hydroxychloroquine alone, hydroxychloroquine + metformin was associated with an ROR value of 57.7 (23.9-139.3). In comparison with metformin alone, hydroxychloroquine + metformin was associated with an ROR value of 6.0 (2.6-13.8). Conclusion Our study identified a signal for the association hydroxychloroquine + metformin that appears to be more at risk of fatal outcomes (particularly by completed suicides) than one of the two drugs when given alone.

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“…Values were expressed as mean ± standard deviation (SD) unless otherwise speciﬁed. Continuous and discrete variables between the SLE and HC groups were compared by using Mann-Whitney U test and χ 2 test, respectively. Correlations between IFC of each protein and demographic and clinical parameters were explored by bivariate correlation analyses.…”

Section: Methodsmentioning

confidence: 99%

Detection of putative autoantibodies in systemic lupus erythematous using a novel native-conformation protein microarray platform

Mak

Kow

Ismail³

et al. 2020

Lupus

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Objective Conventional immunoassays detect autoantibodies related to systemic lupus erythematosus (SLE) via recognition of epitopes on autoantigens expressed in their denatured rather than native conformational state, casting difficulty in evaluating the genuine pathogenicity of the autoantibodies. We aimed to use a novel high-throughput protein microarray platform to identify autoantibodies against native autoantigens in SLE sera. Methods Sera from SLE patients and those of gender-, age-, and ethnicity-matched healthy controls (HC) were screened against more than 1,600 immune-related antigens of native conformation. The relative fluorescent unit readout from post-assay imaging were subjected to bioinformatics pre-processing and composite normalization. A penetrance fold change (pFC) analysis between SLE and HC samples shortlisted 50 autoantigens that were subjected to an unsupervised cluster analysis. Correlations between the pFC of putative autoantigens and clinical parameters including SLE disease activity index (SLEDAI-2K) and recent SLE flares were explored. Results 381 autoantigens were identified when 15 SLE and 15 HC serum samples were compared. The top 20 autoantigens which elicited autoantibody responses in SLE sera filtered based on the highest pFC were further analyzed. Autoantigens which the putative autoantibodies reacted against are those involved in chromatin organization such as DEK, regulation of transcription activity including REOX4 and ELF4, and negative regulation of NFkB activity such as TRIB3. Additionally, the pFC of these autoantibodies significantly and positively correlated with SLEDAI-2K and recent SLE flares. Conclusion A high-throughput protein microarray platform allows detection and quantification of putative lupus-related autoantibodies which are of potential pathophysiological and prognostic significance in SLE patients.

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The Potential Use of Metformin, Dipyridamole, N-Acetylcysteine and Statins as Adjunctive Therapy for Systemic Lupus Erythematosus

Cited by 27 publications

References 96 publications

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

A New Drug–Drug Interaction Between Hydroxychloroquine and Metformin? A Signal Detection Study

Detection of putative autoantibodies in systemic lupus erythematous using a novel native-conformation protein microarray platform

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