Evaluation of genotoxic effect via expression of DNA damage responsive gene induced by ivermectin on MDBK cell line

Evaluation of genotoxic effect via expression of DNA damage responsive gene induced by ivermectin on MDBK cell line

Ivermectin (IVM) is an anti-parasitic drug which is used for treating parasitic infestations. It has been used in humans for treating intestinal strongyloidiasis and onchocerciasis however, currently researchers are investigating its potential for treating coronavirus SARS-CoV-2. Due to its broad-sp...

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Bibliographic Details
Published in:PloS one Vol. 19; no. 5; p. e0296255
Main Authors: Ali, Muhammad Muddassir, Farhad, Zainab, Wasim, Muhammad, Raza, Sohail, Almutairi, Mikhlid H, Zahra, Kainat, Saleem, Muhammad Usman, Mehmood, Khalid
Format: Journal Article
Language:English
Published: United States Public Library of Science 03-05-2024
Public Library of Science (PLoS)
Subjects:
Analysis
Animals
Antiparasitic agents
Antiparasitic Agents - pharmacology
Antiparasitic Agents - toxicity
Assaying
Bioassays
Bromides
Cattle
Causes of
Cell Line
Cell Survival - drug effects
Cell viability
Cells
Comet Assay
Complications and side effects
Coronaviruses
Cytotoxicity
Damage detection
Deoxyribonucleic acid
DNA
DNA damage
DNA Damage - drug effects
DNA Glycosylases - genetics
DNA Glycosylases - metabolism
DNA repair
Evaluation
FDA approval
Gene expression
Genes
Genetic aspects
Genetic research
Genotoxicity
Health aspects
Ivermectin
Ivermectin - pharmacology
Ivermectin - toxicity
Kidney - cytology
Kidney - drug effects
Micronucleus Tests
Mutagens - toxicity
OGG1 protein
Onchocerciasis
Parasites
Polymerase chain reaction
RNA
Severe acute respiratory syndrome coronavirus 2
Strongyloidiasis
Toxicity testing
Pakistan
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Summary:Ivermectin (IVM) is an anti-parasitic drug which is used for treating parasitic infestations. It has been used in humans for treating intestinal strongyloidiasis and onchocerciasis however, currently researchers are investigating its potential for treating coronavirus SARS-CoV-2. Due to its broad-spectrum activities, IVM is being used excessively in animals which has generated an interest for researchers to investigate its toxic effects. Cytotoxic and genotoxic effects have been reported in animals due to excessive usage of IVM. Therefore, this study aims to evaluate the cytotoxic and genotoxic effects of IVM on the Madin-Darby-Bovine-Kidney (MDBK) cell line by examining the expression of a DNA damage-responsive gene (OGG1). Cytotoxicity of IVM was tested using an assay (MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), whereas the genotoxicity was evaluated using comet assay along with micronucleus assay. Moreover, the gene expression of DNA damage response gene (OGG1) was measured by qRT-PCR, after extraction of RNA from the MDBK cell line using the TRIzol method and its conversion to cDNA by reverse-transcriptase PCR. During the experiment, cell viability percentage was measured at different doses of IVM i.e., 25%, 50%, 75%, along with LC50/2, LC50 and LC50*2. It was observed that the gene expression of OGG1 increased as the concentration of IVM increased. It was concluded that IVM has both cytotoxic and genotoxic effects on the MDBK cell line. Furthermore, it is recommended that studies related to the toxic effects of IVM at molecular level and on other model organisms should be conducted to combat its hazardous effects.
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ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0296255