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

• 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
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0296255

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.