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Sankar, Sudharsan, Redipalli, Sharmishta, Jayaraj, Indhuja, Ghosal, Soumika, Parvathi, Venkatachalam Deepa. (1403). Evaluating the Genotoxicity of Hydroxychloroquine: An In Vitro and In Vivo Study. سامانه مدیریت نشریات علمی, 12(3), 251-259. doi: 10.30476/jhsss.2023.99791.1815
Sudharsan Sankar; Sharmishta Redipalli; Indhuja Jayaraj; Soumika Ghosal; Venkatachalam Deepa Parvathi. "Evaluating the Genotoxicity of Hydroxychloroquine: An In Vitro and In Vivo Study". سامانه مدیریت نشریات علمی, 12, 3, 1403, 251-259. doi: 10.30476/jhsss.2023.99791.1815
Sankar, Sudharsan, Redipalli, Sharmishta, Jayaraj, Indhuja, Ghosal, Soumika, Parvathi, Venkatachalam Deepa. (1403). 'Evaluating the Genotoxicity of Hydroxychloroquine: An In Vitro and In Vivo Study', سامانه مدیریت نشریات علمی, 12(3), pp. 251-259. doi: 10.30476/jhsss.2023.99791.1815
Sankar, Sudharsan, Redipalli, Sharmishta, Jayaraj, Indhuja, Ghosal, Soumika, Parvathi, Venkatachalam Deepa. Evaluating the Genotoxicity of Hydroxychloroquine: An In Vitro and In Vivo Study. سامانه مدیریت نشریات علمی, 1403; 12(3): 251-259. doi: 10.30476/jhsss.2023.99791.1815

Evaluating the Genotoxicity of Hydroxychloroquine: An In Vitro and In Vivo Study

Journal of Health Sciences & Surveillance System
دوره 12، شماره 3، مهر 2024، صفحه 251-259    اصل مقاله (1.34 M)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.30476/jhsss.2023.99791.1815
نویسندگان
Sudharsan Sankar1؛ Sharmishta Redipalli1؛ Indhuja Jayaraj2؛ Soumika Ghosal1؛ Venkatachalam Deepa Parvathi* 1
1Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Ramachandra Nagar, Porur, Chennai-600116 Tamil Nadu, India
21Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Ramachandra Nagar, Porur, Chennai-600116 Tamil Nadu, India
چکیده
Background: Hydroxychloroquine (HCQ) is a drug used to treat malarial parasites and it was extensively used during the initial phase of COVID-19. However, HCQ demonstrated certain serious effects when administered to patients. Hence, this study intends to determine its toxicity by exposing it to human peripheral blood and the fly model.
Methods: In the present experimental study, HCQ (200 mg) was tested in different volumes (62.5 μl - 500 μl) on human blood samples (in vitro) and Drosophila melanogaster (in vivo). Hemolytic assay, trypan blue assay, mitotic index, chromosomal aberration, and DNA fragmentation assay were used to assess the sublethal effects of HCQ.
Results: The results implied that HCQ, at its highest concentration (500 μl), showed maximum lysis in the hemolytic assay, and an increased number of dead cells were observed with increasing concentration in trypan blue assay. Also, the percent mitotic index decreased with increasing concentration of HCQ. Chromosomal aberrations, including breaks, centromeric disruption, dicentrics, and pulverized chromosomes, were observed on exposure to HCQ. The number of fragments in agarose gel electrophoresis revealed damage to DNA. Therefore, these results provide evidence and prove the cytotoxicity and genotoxicity of HCQ.
Conclusion: HCQ is found to have cytotoxic and genotoxic effects. These results imply that further examinations must be conducted before prescribing HCQ to treat various diseases.

تازه های تحقیق

Sudharsan Sankar (Google Scholar)

Venkatachalam Deepa Parvathi (Google Scholar)

کلیدواژه‌ها
Drosophila melanogaster؛ Cytotoxicity؛ Human peripheral blood؛ Genotoxicity؛ Hydroxychloroquine
مراجع
  1. Lei ZN, Wu ZX, Dong S, Yang DH, Zhang L, Ke Z, Zou C, Chen ZS. Chloroquine and hydroxychloroquine in the treatment of malaria and repurposing in treating COVID-19. Pharmacology & Therapeutics. 2020. 216:107672. doi: 10.1016/j.pharmthera.2020.107672. PMID: 32910933. PMCID: PMC7476892.
  2. Fox RI. Mechanism of action of hydroxychloroquine as an antirheumatic drug. InSeminars in arthritis and rheumatism 1993. 23, 2; 82-91. WB Saunders. doi: 10.1016/S0049-0172(10)80012-5.
  3. Coban C. The host targeting effect of chloroquine in malaria. Current opinion in immunology. 2020. 66:98-107. doi: 10.1016/j.coi.2020.07.005.
  4. Hydroxychloroquine. pubchem.ncbi.nlm.nih.gov. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Hydroxychloroquine#section=Canonical-SMILES
  5. Stokkermans TJ, Falkowitz DM, Trichonas G. Chloroquine and Hydroxychloroquine Toxicity. Treasure Island (FL): StatPearls Publishing; 2024. PMID: 30725771.
  6. Saber S, Khodir AE, Maghmomeh AO, Nouh NA, El-Baz AM. COVID-19 Pandemic: current Challenges and future Perspectives. Research Journal of Pharmacy and Technology. 2022;15(1):329-37. doi: 10.3390/ph14040341. PMID: 33917884. PMCID: PMC8068273.
  7. Singh AK, Singh A, Shaikh A, Singh R, Misra A. Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020;14(3):241-6. doi: 10.1016/j.dsx.2020.03.011. PMID: 32247211. PMCID: PMC7102587.
  8. FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems. FDA [Internet]. 2020 Apr 24; Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or.‌
  9. Sanyaolu A, Okorie C, Marinkovic A, Patidar R, Younis K, Desai P, Hosein Z, Padda I, Mangat J, Altaf M. Comorbidity and its impact on patients with COVID-19. SN comprehensive clinical medicine. 2020; 2(8):1069-76. doi: 10.1007/s42399-020-00363-4. PMID: 32838147. PMCID: PMC7314621.
  10. Gevers S, Kwa MS, Wijnans E, Van Nieuwkoop C. Safety considerations for chloroquine and hydroxychloroquine in the treatment of COVID-19. Clinical Microbiology and Infection. 2020; 26(9):1276-7. doi: 10.1016/j.cmi.2020.05.006. PMID: 32422406. PMCID: PMC7228887.
  11. Eftekhar SP, Kazemi S, Barary M, Javanian M, Ebrahimpour S, Ziaei N. Effect of hydroxychloroquine and azithromycin on QT interval prolongation and other cardiac arrhythmias in COVID-19 confirmed patients. Cardiovascular therapeutics. 2021; 2021. doi: 10.1155/2021/6683098. PMID: 33688374. PMCID: PMC7924072.
  12. Yang J, Guo Z, Liu X, Liu Q, Wu M, Yao X, Liu Y, Cui C, Li H, Song C, Liu D. Cytotoxicity evaluation of chloroquine and hydroxychloroquine in multiple cell lines and tissues by dynamic imaging system and physiologically based pharmacokinetic model. Frontiers in Pharmacology. 2020; 11:574720. doi: 10.3389/fphar.2020.574720. PMID: 33658924. PMCID: PMC7919379.
  13. Besaratinia A, Caliri AW, Tommasi S. Hydroxychloroquine induces oxidative DNA damage and mutation in mammalian cells. DNA repair. 2021; 106:103180. doi: 10.1016/j.dnarep.2021.103180. PMID: 34298488. PMCID: PMC8435022.
  14. Brambilla G, Martelli A. Genotoxic and carcinogenic risk to humans of drug–nitrite interaction products. Mutation Research/Reviews in Mutation Research. 2007; 635(1):17-52. doi: 10.1016/j.mrrev.2006.09.003. PMID: 17157055.
  15. Giri A, Das A, Sarkar AK, Giri AK. Mutagenic, Genotoxic and Immunomodulatory effects of Hydroxychloroquine and Chloroquine: a review to evaluate its potential to use as a prophylactic drug against COVID-19. Genes and Environment. 2020; 42(1):1-4. doi: 10.1186/s41021-020-00164-0. PMID: 32884603. PMCID: PMC7462746.
  16. Thillainayagam M, Ramaiah S. Mosquito, malaria and medicines-A review. Research Journal of Pharmacy and Technology. 2016; 9(8):1268-76. doi: 10.5958/0974-360X.2016.00241.9.
  17. Pandey AV, Chauhan VS. Heme polymerization by malarial parasite: a potential target for antimalarial drug development. Current Science. 1998; 911-8. https://www.jstor.org/stable/24101665.
  18. Homewood CA, Warhurst DC, Peters W, Baggaley VC. Lysosomes, pH and the anti-malarial action of chloroquine. Nature. 1972; 235(5332):50-2. doi: 1038/235050a0. PMID: 4550396.
  19. Roldan EQ, Biasiotto G, Magro P, Zanella I. The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? Pharmacological research. 2020; 158:104904. doi: 10.1016/j.phrs.2020.104904. PMID: 32430286. PMCID: PMC7217799.
  20. Nirk EL, Reggiori F, Mauthe M. Hydroxychloroquine in rheumatic autoimmune disorders and beyond. EMBO molecular medicine. 2020; 12(8): e12476. doi: 10.15252/emmm.202012476. PMID: 32715647. PMCID: PMC7411564.
  21. Jothivel N, Singaravel S, Deivasigamani K, Vasudevan M, Sundaram S, Sambasivam N, Thangavel S. Follow-Up of Combination of Chloroquine with Anti-Viral Drugs Treated Chronic Hepatitis ‘B’Patients for Their Carrier State. Research Journal of Pharmacy and Technology. 2008;1(3):259-. https://rjptonline.org/HTML_Papers/Research%20Journal%20of%20Pharmacy%20and%20Technology__PID__2008-1-3-67.html.
  22. Roldan EQ, Biasiotto G, Magro P, Zanella I. The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? Pharmacological research. 2020; 158:104904. doi: 10.1016/j.phrs.2020.104904. PMID: 32430286. PMCID: PMC7217799.
  23. Satarker S, Ahuja T, Banerjee M, Dogra S, Agarwal T, Nampoothiri M. Hydroxychloroquine in COVID-19: potential mechanism of action against SARS-CoV-2. Current pharmacology reports. 2020; 6(5):203-11. doi: 10.1007/s40495-020-00231-8. PMID: 32864299. PMCID: PMC7443392.
  24. Alaraj M. Pharmacological repurposed agents for COVID-19. Research Journal of Pharmacy and Technology. 2022;15(1):441-6. doi: 10.52711/0974-360X.2022.00073.
  25. Sun J, Chen Y, Fan X, Wang X, Han Q, Liu Z. Advances in the use of chloroquine and hydroxychloroquine for the treatment of COVID-19. Postgraduate medicine. 2020; 132(7):604-13. doi: 10.1080/00325481.2020.1778982. PMID: 32496926. PMCID: PMC7441788.
  26. Amin M, Abbas G. Docking study of chloroquine and hydroxychloroquine interaction with RNA binding domain of nucleocapsid phospho-protein–an in silico insight into the comparative efficacy of repurposing antiviral drugs. Journal of Biomolecular Structure and Dynamics. 2021; 39(12):4243-55. doi: 10.1080/07391102.2020.1775703. PMID: 32469265.
  27. Vaishnav Y, Banjare L, Verma S, Sharma G, Biswas D, Tripathi A, Shaik AB, Bhandare RR, Kaur A, Manjunath K. Computational Method on Hydroxychloroquine and Azithromycin for SARS-CoV-2: Binding Affinity Studies. Research Journal of Pharmacy and Technology. 2022;15(12):5467-72. doi: 10.52711/0974-360X.2022.00922.
  28. Pandey A, Nikam AN, Shreya AB, Mutalik SP, Gopalan D, Kulkarni S, Padya BS, Fernandes G, Mutalik S, Prassl R. Potential therapeutic targets for combating SARS-CoV-2: Drug repurposing, clinical trials and recent advancements. Life sciences. 2020; 256:117883. doi: 10.1016/j.lfs.2020.117883. PMID: 32497632. PMCID: PMC7263255.
  29. Oscanoa TJ, Romero-Ortuno R, Carvajal A, Savarino A. A pharmacological perspective of chloroquine in SARS-CoV-2 infection: An old drug for the fight against a new coronavirus? International journal of antimicrobial agents. 2020; 56(3):106078. doi: 10.1016/j.ijantimicag.2020.106078. PMID: 32629115.PMCID: PMC7334645.
  30. Goldman FD, Gilman AL, Hollenback C, Kato RM, Premack BA, Rawlings DJ. Hydroxychloroquine inhibits calcium signals in T cells: a new mechanism to explain its immunomodulatory properties. Blood, The Journal of the American Society of Hematology. 2000; 95(11):3460-6. doi: 10.1182/blood.V95.11.3460. PMID: 10828029.
  31. Schaper C. A Mechanism of Action for Hydroxychloroquine and Azithromycin to Inhibit Coronavirus Disease COVID-19. https://chemrxiv.org/engage/chemrxiv/article-details/60c74a1ef96a004b00287395.
  32. Lee HO, Mustafa A, Hudes GR, Kruger WD. Hydroxychloroquine destabilizes phospho-S6 in human renal carcinoma cells. PLoS One. 2015; 10(7): e0131464. doi: 10.1371/journal.pone.0131464. PMID: 26134285. PMCID: PMC4489871.
  33. Cook KL, Wärri A, Soto-Pantoja DR, Clarke PA, Cruz MI, Zwart A, Clarke R. Chloroquine inhibits autophagy to potentiate antiestrogen responsiveness in ER+ breast cancer. Clinical Cancer Research. 2014; 20(12):3222-32. doi: 10.1158/1078-0432.CCR-13-3227. PMID: 24928945. PMCID: PMC4073207.
  34. Meng XW, Feller JM, Ziegler JB, Pittman SM, Ireland CM. Induction of apoptosis in peripheral blood lymphocytes following treatment in vitro with hydroxychloroquine. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 1997; 40(5):927-ref. doi: 10.1002/art.1780400522. PMID: 9153556.
  35. Dagur PK, McCoy Jr JP. Collection, storage, and preparation of human blood cells. Current protocols in cytometry. 2015; 73(1):5-1.
  36. Cowan JF, Khan MB, Vargo J, Joist JH. An improved method for evaluation of blood coagulation in heparinized blood. American Journal of Clinical Pathology. 1981; 75(1):60-4.
  37. Gautam A. Phenol-chloroform DNA isolation Method. InDNA and RNA Isolation Techniques for Non-Experts. 2022; 33-39. Cham: Springer International Publishing.
  38. Chansky PB, Werth VP. Accidental hydroxychloroquine overdose resulting in neurotoxic vestibulopathy. Case Reports. 2017; bcr-2016. doi: 10.1136/bcr-2016-218786. PMID: 28404567. PMCID: PMC5534916.
  39. Sasi S, Yassin MA, Nair AP, Al Maslamani MS. A case of COVID-19 in a patient with asymptomatic hemoglobin D thalassemia and glucose-6-phosphate dehydrogenase deficiency. The American Journal of Case Reports. 2020;21: e925788-1. doi: 10.12659/AJCR.925788. PMID: 32697769. PMCID: PMC7394553.
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