Publication:
Favipiravir Induces Oxidative Stress and Genotoxicity in Cardiac and Skin Cells.

Simple item page
dc.contributor.authorGunaydin-Akyildiz, AYŞENUR
dc.contributor.authorAksoy, Nergis
dc.contributor.authorBoran, Tugce
dc.contributor.authorIlhan, Emine Nihan
dc.contributor.authorOzhan, Gul
dc.contributor.institutionauthorGÜNAYDIN AKYILDIZ, AYŞENUR
dc.date.accessioned2022-10-01T20:59:08Z
dc.date.available2022-10-01T20:59:08Z
dc.date.issued2022-09-21T00:00:00Z
dc.description.abstractFavipiravir (T-705), used against influenza viruses, is approved for emergency use in many countries for the treatment of COVID-19. The frequent adverse effects of favipiravir are related with the gastrointestinal system, however, studies suggest a positive association of favipiravir on QTc prolongation, which can cause cardiotoxicity. Also, there are reports of skin reactions such as angioedema due to favipiravir. Despite the several adverse effects, studies examining the drug's effects at the molecular level are insufficient, e.g., the genotoxic and oxidative stress-inducing effects of favipiravir, which are among the primary mechanisms of drug-induced toxicity. The cytotoxicity of favipiravir was analyzed with the measurement of the ATP content in H9c2 cardiomyoblasts and CCD-1079Sk skin fibroblasts. The ATP level decreased starting from 200 µM. The inhibitory effect on the mitochondrial electron transport chain enzymes complex I and complex V was also evaluated where favipiravir showed significant enzyme inhibitory effects in the highest concentration studied. A molecular docking study evaluating the interaction between favipiravir-RTP and mitochondrial DNA polymerase (POLG1) was done. The relationship of favipiravir with oxidative stress was examined by measuring glutathione (GSH) and protein carbonyl levels which were observed higher after drug treatment compared to the control group. The genotoxicity study was done using the Comet assay and increase in DNA tail has been detected. Furthermore, 8-OHdG levels were measured higher in favipiravir treated cells indicating oxidative DNA damage. Favipiravir induced oxidative stress leading to DNA damage in cardiomyoblast cells and fibroblastic skin cells. Oxidative stress and DNA damage might eventually lead to organ-specific damage such as cardiotoxicity and dermal toxicity. Considering the increased use of favipiravir in recent years, and that oxidative stress and genotoxicity are two important indicators of drug-induced toxicity, the obtained results are worth attention.
dc.identifier.citationGunaydin-Akyildiz A., Aksoy N., Boran T., Ilhan E. N. , Ozhan G., -Favipiravir Induces Oxidative Stress and Genotoxicity in Cardiac and Skin Cells.-, Toxicology letters, 2022
dc.identifier.doi10.1016/j.toxlet.2022.09.011
dc.identifier.pubmed36152797
dc.identifier.pubmed36152797
dc.identifier.scopus85139027531
dc.identifier.urihttp://hdl.handle.net/20.500.12645/31047
dc.identifier.wosWOS:000876943100001
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCardiotoxicity
dc.subjectDNA damage
dc.subjectDermal toxicity
dc.subjectFavipiravir
dc.subjectGenotoxicity
dc.subjectMitochondrial toxicity
dc.subjectOxidative stress
dc.titleFavipiravir Induces Oxidative Stress and Genotoxicity in Cardiac and Skin Cells.
dc.typeArticle
dspace.entity.typePublication
local.avesis.id53fbd212-3f79-4268-a494-77100f195248
local.publication.isinternational1
relation.isAuthorOfPublication98a70592-2158-4e37-b8d7-80d3bd64c98c
relation.isAuthorOfPublication.latestForDiscovery98a70592-2158-4e37-b8d7-80d3bd64c98c
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
1-s2.0-S0378427422017477-main.pdf
Size:
2.14 MB
Format:
Adobe Portable Document Format
Download
Collections
Yayınlar - Eserler