Exploring insights of hydroxychloroquine, a controversial drug in Covid-19: An update

Joshi, Gaurav; Thakur, Shikha; Mayank, .; Ramarao, P.

doi:10.1016/j.fct.2021.112106

Cited by 6 publications

(4 citation statements)

References 106 publications

(81 reference statements)

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“…The recommended dosage of HCQ in COVID-19 patients is generally higher than that in autoimmune disease but in shorter duration, e.g., an initial loading dose (for up to a few days), followed by several days of maintenance dosing [60][61][62]. The administered doses of HCQ in our study are comparable to the therapeutic doses used in patient populations [25,57,[63][64][65], as described above.…”

Section: Discussionsupporting

confidence: 66%

“…Notably, the observed genotoxic effects of HCQ are manifest at clinically achievable doses. Given the substantial number of the world's population receiving HCQ for the treatment of various chronic diseases [19] or in the context of clinical trials for COVID-19 [3][4][5][6][63][64][65], our findings warrant further investigations into the biological consequences of therapeutic/preventive use of this drug.…”

Section: Discussionmentioning

confidence: 89%

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Hydroxychloroquine induces oxidative DNA damage and mutation in mammalian cells

2021

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Since the early stages of the pandemic, hydroxychloroquine (HCQ), a widely used drug with good safety profile in clinic, has come to the forefront of research on drug repurposing for COVID-19 treatment/prevention. Despite the decades-long use of HCQ in the treatment of diseases, such as malaria and autoimmune disorders, the exact mechanisms of action of this drug are only beginning to be understood. To date, no data are available on the genotoxic potential of HCQ in vitro or in vivo. The present study is the first investigation of the DNA damagingand mutagenic effects of HCQ in mammalian cells in vitro, at concentrations that are comparable to clinically achievable doses in patient populations. We demonstrate significant induction of a representative oxidative DNA damage (8-oxodG) in primary mouse embryonic fibroblasts (MEFs) treated with HCQ at 5 and 25 μM concentrations (P = 0.020 and P = 0.029, respectively), as determined by enzyme-linked immunosorbent assay. Furthermore, we show significant mutagenicity of HCQ, manifest as 2.2-and 1.8-fold increases in relative cII mutant frequency in primary and spontaneously immortalized Big Blue® MEFs, respectively, treated with 25 μM dose of this drug (P = 0.005 and P = 0.012, respectively). The observed genotoxic effects of HCQ in vitro, achievable at clinically relevant doses, are novel and important, and may have significant implications for safety monitoring in patient populations. Given the substantial number of the world's population receiving HCQ for the treatment of various chronic diseases or in the context of clinical trials for COVID-19, our findings warrant further investigations into the biological consequences of therapeutic/preventive use of this drug.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 89%

Hydroxychloroquine induces oxidative DNA damage and mutation in mammalian cells

2021

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“…47 The national health commission of China issued Guidelines for the Diagnosis, Prevention, and Treatment of COVID-19, which included HCQ as an antidote in the cure protocol 48 followed by permitted approval of the United States Food and Drug Administration for prescribing HCQ for treating COVID-19 patients. 49 Consequently, health organizations often recommend this medication as a treatment protocol for COVID-19. On the contrary, the long-term use of this drug in high dosages causes various chronic adversative health impacts including intravascular hemolysis, cardiomyopathy, bone marrow suppression, neurological reactions, gastrointestinal toxicity, hypoglycemia, ventricular arrhythmias, kidney failure and even unexpected death.…”

Section: Environmental Science: Nano Papermentioning

confidence: 99%

Alkaline earth metal stannate TSnO₃ (T = Ca and Sr) entrapped functionalized carbon nanofiber composites: active electrocatalysts for the determination of hydroxychloroquine in environmental samples

Sherlin¹,

Sriram²,

Wang³

et al. 2023

Environ. Sci.: Nano

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“…In the pandemic period, controversy existed over the safety and effectiveness of repurposed medications, nutraceuticals, supplements, and alternative therapies. Two of the most salient examples were hydroxychloroquine [40] and ivermectin [41]. Some therapeutics with strong supporting evidence, such as ivermectin for the prevention and treatment of COVID-19, were restricted under legal penalty [42], despite evidence of their treatment and prophylactic efficacy [43].…”

Section: Introduction: a Loss Of Trustmentioning

confidence: 99%

Public Health Needs the Public Trust: A Pandemic Retrospective

Halma¹,

Guetzkow

2023

BioMed

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The COVID crisis of the past three years has greatly impacted stakeholder relationships between scientists, health providers, policy makers, pharmaceutical industry employees, and the public. Lockdowns and restrictions of civil liberties strained an already fraught relationship between the public and policy makers, with scientists also seen as complicit in providing the justification for the abrogation of civil liberties. This was compounded by the suppression of open debate over contentious topics of public interest and a violation of core bioethical principles embodied in the Nuremberg Code. Overall, the policies chosen during the pandemic have had a corrosive impact on public trust, which is observable in surveys and consumer behaviour. While a loss of trust is difficult to remedy, the antidotes are accountability and transparency. This narrative review presents an overview of key issues that have motivated public distrust during the pandemic and ends with suggested remedies. Scientific norms and accountability must be restored in order to rebuild the vital relationship between scientists and the public they serve.

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Exploring insights of hydroxychloroquine, a controversial drug in Covid-19: An update

Cited by 6 publications

References 106 publications

Hydroxychloroquine induces oxidative DNA damage and mutation in mammalian cells

Hydroxychloroquine induces oxidative DNA damage and mutation in mammalian cells

Alkaline earth metal stannate TSnO₃ (T = Ca and Sr) entrapped functionalized carbon nanofiber composites: active electrocatalysts for the determination of hydroxychloroquine in environmental samples

Public Health Needs the Public Trust: A Pandemic Retrospective

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Exploring insights of hydroxychloroquine, a controversial drug in Covid-19: An update

Cited by 6 publications

References 106 publications

Hydroxychloroquine induces oxidative DNA damage and mutation in mammalian cells

Hydroxychloroquine induces oxidative DNA damage and mutation in mammalian cells

Alkaline earth metal stannate TSnO3 (T = Ca and Sr) entrapped functionalized carbon nanofiber composites: active electrocatalysts for the determination of hydroxychloroquine in environmental samples

Public Health Needs the Public Trust: A Pandemic Retrospective

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Alkaline earth metal stannate TSnO₃ (T = Ca and Sr) entrapped functionalized carbon nanofiber composites: active electrocatalysts for the determination of hydroxychloroquine in environmental samples