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All Studies   Meta Analysis    Recent:   

Paracetamol-Induced Glutathione Consumption: Is There a Link With Severe COVID-19 Illness?

Sestili et al., Frontiers in Pharmacology, doi:10.3389/fphar.2020.579944
Oct 2020  
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1st treatment shown to increase risk in November 2020
 
*, now known with p = 0.00000029 from 28 studies, but still recommended in 46 countries.
* From meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments. c19early.org
Discussion of the potential negative effects of acetaminophen for COVID-19 based on promotion of glutathione depletion, especially in population groups at higher risk.
Reviews covering acetaminophen for COVID-19 include Fazio, Pandolfi, Pandolfi (B), Sestili.
Acetaminophen is also known as paracetamol, Tylenol, Panadol, Calpol, Tempra, Calprofen, Doliprane, Efferalgan, Grippostad C, Dolo, Acamol, Fevadol, Crocin, and Perfalgan.
Sestili et al., 7 Oct 2020, peer-reviewed, 2 authors. Contact: piero.sestili@uniurb.it.
This PaperAcetaminophenAll
Paracetamol-Induced Glutathione Consumption: Is There a Link With Severe COVID-19 Illness?
Piero Sestili, Carmela Fimognari
Frontiers in Pharmacology, doi:10.3389/fphar.2020.579944
COVID-19 pandemic is posing an unprecedented sanitary threat: antiviral and hostdirected medications to treat the disease are urgently needed. A great effort has been paid to find drugs and treatments for hospitalized, severely ill patients. However, medications used for the domiciliary management of early symptoms, notwithstanding their importance, have not been and are not presently regarded with the same attention and seriousness. In analogy with other airways viral infections, COVID-19 patients in the early phase require specific antivirals (still lacking) and non-etiotropic drugs to lower pain, fever, and control inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol (PAC) are widely used as non-etiotropic agents in common airways viral infections and hence are both theoretically repurposable for COVID-19. However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of angiotensin-converting enzyme 2 (ACE2) levels (the receptor used by SARS-CoV2 to enter host airways cells), the increased risk of bacterial superinfections and masking of disease symptoms. As a consequence, the use of NSAIDs was, and is still, discouraged while the alternative adoption of paracetamol is still preferred. On the basis of novel data and hypothesis on the possible role of scarce glutathione (GSH) levels in the exacerbation of COVID-19 and of the GSH depleting activity of PAC, this commentary raises the question of whether PAC may be the better choice.
AUTHOR CONTRIBUTIONS PS: conceptualization and writing. CF: bibliographic search, revision of the text. All authors contributed to the article and approved the submitted version. Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
Aktas, Aslim, Gut-lung axis and dysbiosis in COVID-19, Turk. J. Biol, doi:10.3906/biy-2005-102
Ali, Relationship Between COVID-19 Infection and Liver Injury: A Review of Recent Data, Front. Med, doi:10.3389/fmed.2020.00458
Aydemir, Ulusu, Is glucose-6-phosphate dehydrogenase enzyme deficiency a factor in Coronavirus-19 (COVID-19) infections and deaths?, Pathog. Glob. Health, doi:10.1080/20477724.2020.1751388
Bolt, Thier, Relevance of the deletion polymorphisms of the glutathione S-transferases GSTT1 and GSTM1 in pharmacology and toxicology, Curr. Drug Metab, doi:10.2174/138920006778017786
Bruce, Barlow-Pay, Short, Vilches-Moraga, Price et al., Prior Routine Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Important Outcomes in Hospitalised Patients with COVID-19, J. Clin. Med, doi:10.3390/jcm9082586
Brune, Renner, Tiegs, Acetaminophen/paracetamol: A history of errors, failures and false decisions, Eur. J. Pain, doi:10.1002/ejp.621
Burgunder, Varriale, Lauterburg, Effect of Nacetylcysteine on plasma cysteine and glutathione following paracetamol administration, Eur. J. Clin. Pharmacol, doi:10.1007/BF00609183
Cantin, Begin, Glutathione and inflammatory disorders of the lung, Lung, doi:10.1007/BF02714149
Cantoni, Sestili, Palomba, Guidarelli, Cattabeni et al., Isolation and preliminary characterization of a Chinese hamster ovary cell line with high-degree resistance to hydrogen peroxide, Biochem. Pharmacol, doi:10.1016/0006-2952(95)02436-0
Capuano, Scavone, Racagni, Scaglione, NSAIDs in patients with viral infections, including Covid-19: Victims or perpetrators?, Pharmacol. Res, doi:10.1016/j.phrs.2020.104849
Cumhur Cure, Kucuk, Cure, NSAIDs may increase the risk of thrombosis and acute renal failure in patients with COVID-19 infection, Therapie, doi:10.1016/j.therap.2020.06.012
Danser, Epstein, Batlle, Renin-Angiotensin System Blockers and the COVID-19 Pandemic: At Present There Is No Evidence to Abandon Renin-Angiotensin System Blockers, Hypertension, doi:10.1161/hypertensionaha.120.15082
Day, Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists, BMJ, doi:10.1136/bmj.m1086
De Flora, Balansky, Maestra, Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19, FASEB J, doi:10.1096/fj.202001807
De Flora, Grassi, Carati, Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with longterm N-acetylcysteine treatment, Eur. Respir. J, doi:10.1183/09031936.97.10071535
De Tours, De Marseille, Rapport d'expertise -Infections bacteŕiennes graves (de la peau et des tissus mous, pleuro-pulmonaires, neurologiques et ORL) rapporteés avec l'ibuprofène ou le ketoprofène dans le traitement symptomatique de la fièvre ou de douleur non rhumatologique
Dimova, Hoet, Dinsdale, Nemery, Acetaminophen decreases intracellular glutathione levels and modulates cytokine production in human alveolar macrophages and type II pneumocytes in vitro, Int. J. Biochem. Cell Biol, doi:10.1016/j.biocel.2005.03.005
Driver, Marks, Van Der Wal, Not all (N)SAID and done: Effects of nonsteroidal anti-inflammatory drugs and paracetamol intake on platelets, Res. Pract. Thromb. Haemost, doi:10.1002/rth2.12283
Estevez, De Angelo, Vesell, Basal and paracetamol-depleted glutathione from human lymphocytes: ethnic variability, Acta Physiol. Pharmacol. Ther. Latinoam
Farouk, Fiaccadori, Cravedi, Campbell, COVID-19 and the kidney: what we think we know so far and what we don't, J. Nephrol, doi:10.1007/s40620-020-00789-y
Fitzgerald, Misguided drug advice for COVID-19, Science, doi:10.1126/science.abb8034
Giardini, Carrer, Casati, Contro, Vergani et al., Increased sFLT1/PlGF ratio in COVID-19: a novel link to Angiotensin II-mediated endothelial dysfunction, Am. J. Hematol, doi:10.1002/ajh.25882
Grant, Lahore, Mcdonnell, Baggerly, Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths, Nutrients, doi:10.3390/nu12040988
Hati, Bhattacharyya, Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin-Converting Enzyme 2 Receptor, ACS Omega, doi:10.1021/acsomega.0c02125
Homma, Fujii, Application of Glutathione as Anti-Oxidative and Anti-Aging Drugs, Curr. Drug Metab, doi:10.2174/1389200216666151015114515
Horowitz, Freeman, Bruzzese, Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases, Respir. Med. Case Rep, doi:10.1016/j.rmcr.2020.101063
Ibrahim, El-Meligi, Abdel-Hamid, Elhendy, Relations between von Willebrand factor, markers of oxidative stress and microalbuminuria in patients with type 2 diabetes mellitus, Med. Sci. Monit
Ibrahim, Perl, Smith, Lewis, Kon et al., Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine, Clin. Immunol, doi:10.1016/j.clim.2020.108544
Jain, Micinski, Huning, Kahlon, Bass et al., Vitamin D and L-cysteine levels correlate positively with GSH and negatively with insulin resistance levels in the blood of type 2 diabetic patients, Eur. J. Clin. Nutr, doi:10.1038/ejcn.2014.114
Jain, Parsanathan, Can Vitamin D and L-Cysteine Co-Supplementation Reduce 25(OH)-Vitamin D Deficiency and the Mortality Associated with COVID-19 in African Americans?, J. Am. Coll. Nutr, doi:10.1080/07315724.2020.1789518
Jothimani, Venugopal, Abedin, Kaliamoorthy, Rela, COVID-19 and the liver, J. Hepatol, doi:10.1016/j.jhep.2020.06.006
Kaufmann, Dorhoi, Hotchkiss, Bartenschlager, Host-directed therapies for bacterial and viral infections, Nat. Rev. Drug Discov, doi:10.1038/nrd.2017.162
Khomich, Kochetkov, Bartosch, Redox biology of respiratory viral infections, Viruses, doi:10.3390/v10080392
Klopcǐc, Poberzňik, Mavri, Dolenc, A quantum chemical study of the reactivity of acetaminophen (paracetamol) toxic metabolite N-acetyl-p-benzoquinone imine with deoxyguanosine and glutathione, Chem. Biol. Interact, doi:10.1016/j.cbi.2015.11.002
Kowalewski, Fina, Słomka, Raffa, Martucci et al., COVID-19 and ECMO: the interplay between coagulation and inflammation-a narrative review, Crit. Care, doi:10.1186/s13054-020-02925-3
Kutti Sridharan, Kotagiri, Chandiramani, Mohan, Vegunta et al., COVID-19 and Avoiding Ibuprofen. How Good Is the Evidence?, Am. J. Ther, doi:10.1097/mjt.0000000000001196
Lee, Therapeutic Modulation of Virus-Induced Oxidative Stress via the Nrf2-Dependent Antioxidative Pathway, Oxid. Med. Cell Longev, doi:10.1155/2018/6208067
Martins-Filho, Do Nascimento-Juńior, Santos, No current evidence supporting risk of using Ibuprofen in patients with COVID-19, Int. J. Clin. Pract, doi:10.1111/ijcp.13576
Mast, Dardevet, Papet, Impact of medication on protein and amino acid metabolism in the elderly: the sulfur amino acid and paracetamol case, Nutr. Res. Rev, doi:10.1017/S0954422418000021
Mcbride, The association of acetaminophen and asthma prevalence and severity, Pediatrics, doi:10.1542/peds.2011-1106
Meltzer, Best, Zhang, Vokes, Arora et al., Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results, JAMA Netw. Open, doi:10.1001/jamanetworkopen.2020.19722
Messika, Sztrymf, Bertrand, Billard-Pomares, Barnaud et al., Risks of nonsteroidal antiinflammatory drugs in undiagnosed intensive care unit pneumococcal pneumonia: younger and more severely affected patients, J. Crit. Care, doi:10.1016/j.jcrc.2014.05.021
Micallef, Soeiro, Jonville-Beŕa, COVID-19 and NSAIDs: Primum non nocere, Therapie, doi:10.1016/j.therap.2020.07.008
Micallef, Soeiro, Jonville-Beŕa, Non-steroidal antiinflammatory drugs, pharmacology, and COVID-19 infection, Therapie, doi:10.1016/j.therap.2020.05.003
Moore, Carleton, Blin, Bosco-Levy, Droz, Does Ibuprofen Worsen COVID-19?, Drug Saf, doi:10.1007/s40264-020-00953-0
Mukhtar, Anwar, Hussain, Rasul, Naqvi et al., Detection of Paracetamol as substrate of the gut microbiome, Pak. J. Pharm. Sci
Nencioni, Iuvara, Aquilano, Ciriolo, Cozzolino et al., Influenza A virus replication is dependent on an antioxidant pathway that involves GSH and Bcl-2, FASEB J, doi:10.1096/fj.02-0508fje
Nuttall, Khan, Thorpe, Langford, Kendall, The impact of therapeutic doses of paracetamol on serum total antioxidant capacity, J. Clin. Pharm. Ther, doi:10.1046/j.1365-2710.2003.00493.x
Nydlova, Vrbova, Cesla, Jankovicǒva, Ventura et al., Comparison of inhibitory effects between acetaminophen-glutathione conjugate and reduced glutathione in human glutathione reductase, J. Appl. Toxicol, doi:10.1002/jat.2914
Pacht, Timerman, Lykens, Merola, Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome, Chest, doi:10.1378/chest.100.5.1397
Palamara, Perno, Aquaro, Buè, Dini et al., Glutathione inhibits HIV replication by acting at late stages of the virus life cycle, AIDS Res. Hum. Retroviruses, doi:10.1089/aid.1996.12.1537
Poggiali, Bastoni, Ioannilli, Vercelli, Magnacavallo, Deep Vein Thrombosis and Pulmonary Embolism: Two Complications of COVID-19 Pneumonia?, Eur. J. Case Rep. Internal Med, doi:10.12890/2020_001646
Polonikov, Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients, ACS Infect. Dis, doi:10.1021/acsinfecdis.0c00288
Pujos-Guillot, Pickering, Lyan, Ducheix, Brandolini-Bunlon et al., Therapeutic paracetamol treatment in older persons induces dietary and metabolic modifications related to sulfur amino acids, Age (Dordr, doi:10.1007/s11357-011-9218-4
Roberts, Delgado Nunes, Buckner, Latchem, Constanti et al., Paracetamol: not as safe as we thought? A systematic literature review of observational studies, Ann. Rheum. Dis, doi:10.1136/annrheumdis-2014-206914
Rothuizen, Livio, Buclin, Drugs that aggravate the course of COVID-19: really?
Saadat, An evidence for correlation between the glutathione Stransferase T1 (GSTT1) polymorphism and outcome of COVID-19, Clin. Chim. Acta, doi:10.1016/j.cca.2020.05.041
Sansgiry, Bhansali, Bapat, Xu, Abuse of over-thecounter medicines: a pharmacist's perspective, Integr. Pharm. Res. Pract, doi:10.2147/iprp.s103494
Schönrich, Raftery, Samstag, Devilishly radical NETwork in COVID-19: Oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression, Adv. Biol. Regul, doi:10.1016/j.jbior.2020.100741
Sestili, Stocchi, Repositioning Chromones for Early Antiinflammatory Treatment of COVID-19, Front. Pharmacol, doi:10.3389/fphar.2020.00854
Shaheen, Sterne, Songhurst, Burney, Frequent paracetamol use and asthma in adults, Thorax, doi:10.1136/thorax.55.4.266
Siddiqi, Mehra, COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal, J. Heart Lung Transplant, doi:10.1016/j.healun.2020.03.012
Smart, Fawkes, A narrative review of the potential pharmacological influence and safety of ibuprofen on coronavirus disease 19 (COVID-19), ACE2, and the immune system: a dichotomy of expectation and reality, Inflammopharmacology, doi:10.1007/s10787-020-00745-z
Soeiro, Bourneau-Martin, Micallef, Jonville-Beŕa, Selected Abstracts from Pharmacology 2019 -Multisource comprehensive review on whether ibuprofen exacerbates bacterial infections, Br. J. Clin. Pharmacol, doi:10.1111/bcp.14266
Soltan-Sharifi, Mojtahedzadeh, Najafi, Reza Khajavi, Reza Rouini et al., Improvement by N-acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione, and extracellular thiol molecules and anti-oxidant power: evidence for underlying toxicological mechanisms, Hum. Exp. Toxicol, doi:10.1177/0960327107083452
Stahl, Yates, Nicholls, Kenna, Coen et al., Systems toxicology: modelling biomarkers of glutathione homeostasis and paracetamol metabolism, Drug Discovery Today Technol, doi:10.1016/j.ddtec.2015.06.003
Sun, Song, Shi, Liu, Li et al., Combination of four clinical indicators predicts the severe/critical symptom of patients infected COVID-19, J. Clin. Virol, doi:10.1016/j.jcv.2020.104431
Tomera, Malone, Kittah, Hospitalized COVID-19 Patients Treated With Celecoxib and High Dose Famotidine Adjuvant Therapy Show Significant Clinical Responses, doi:10.2139/ssrn.3646583
Vaja, Chan, Ferreira, Harky, Rogers et al., The COVID-19 ibuprofen controversy: A systematic review of NSAIDs in adult acute lower respiratory tract infections, Br. J. Clin. Pharmacol, doi:10.1111/bcp.14514
Verdecchia, Cavallini, Spanevello, Angeli, The pivotal link between ACE2 deficiency and SARS-CoV-2 infection, Eur. J. Intern. Med, doi:10.1016/j.ejim.2020.04.037
Veronese, Demurtas, Yang, Tonelli, Barbagallo et al., Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature, Front. Med, doi:10.3389/fmed.2020.00170
Violi, Loffredo, Carnevale, Pignatelli, Pastori, Atherothrombosis and Oxidative Stress: Mechanisms and Management in Elderly, Antioxid. Redox Signal, doi:10.1089/ars.2016.6963
Zolk, Hafner, Schmidt, COVID-19 pandemic and therapy with ibuprofen or renin-angiotensin system blockers: no need for interruptions or changes in ongoing chronic treatments, Naunyn Schmiedebergs Arch. Pharmacol, doi:10.1007/s00210-020-01890-6
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