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Case Report
Volume 5 Issue 5 - 2020
Genotoxicity and Cytotoxicity of Nintedanib Exposure in Germ Cells of Mice: Quercetin from Onion Extracts Intervention
Ojo Olajumoke and Daramola*, Oluwakemi Eunice and Oyebanji Olufisayo Grace
Department of Biochemistry, Faculty of Science, Ekiti State University Ado-Ekiti, Ekiti State, Nigeria
*Corresponding Author: Ojo Olajumoke and Daramola, Department of Biochemistry, Faculty of Science, Ekiti State University Ado-Ekiti, Ekiti State, Nigeria.
Received: March 08, 2019; Published: April 10, 2020




Abstract

Nintedanib (NTD) is an orally bioavailable, indolinone-derived, receptor tyrosine kinase (RTK) inhibitor with potential antiangiogenic and antineoplastic activities. However, cases of its toxicity have been reported (Motoyasu., et al. 2019). Hence, this study focused on investigating the genotoxic and cytotoxic effects of Nintedanib and possible protective roles of onion (Allium cepa) extract (OE) and quercetin (QUC) in-vivo. Experimental mice were randomly divided into eight groups (n = 5). Group I served as control, group II and III received 10 mg/kg/bwt QUC and OE; groups IV, V and VI were treated with 5, 10 and 20 mg/kg/bwt NTD respectively while 20 mg/kg/bwt NTD were co- treated with 10 mg/kg/bwt of QUC and OE in group VII and VIII respectively via intraperitoneal route for fourteen days. Effect of Nintedanib and potential ameliorative effect of quercetin and onion extract were evaluated in testicular tissue of mice by measuring enzymatic and non-enzymatic oxidative stress biomarkers. Malondialdehyde (MDA) and reactive oxygen species (ROS) levels were measured using spectrophotometry methods. Sperm count, motility and sperm head morphology; viability cells, sperm comet and halo assay and histology of testes were also evaluated. Nintedanib treatments caused reduce epididymal sperm count, motility; viability of spermatozoa cells with increased sperm morphological abnormalities in dose-dependent pattern, confirming the cytotoxicity of NTD following its exposure in mice, however, significant recovery was seen in the groups co-treated with quercetin and onion extract. Induction of oxidative stress was confirmed by raised reactive oxygen species and MDA levels when compared with the control; quercetin and onion extract treatments significantly (p < 0.05) improved the anti-oxidative biomarkers as compared to only NTD-treated mice. The result of comet assay showed that QUC and OE treatments significantly restored the sperm DNA damage induced by Nintedanib. Further, these flavonoid treatments showed protection against NTD-induced testicular toxicity as evident from testes histology. This study has shown that quercetin and onion extract could proffer a measure of protection against cytotoxicity and genotoxicity caused by nintedanib-treatment which lead to testicular oxidative damage by increasing the antioxidant defense mechanism in mice.

Keywords: Nintedanib; Quercetin; Onion Extract; Genotoxicity; Cytotoxicity; Germ Cell

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Citation: Ojo Olajumoke and Daramola., et al. “Genotoxicity and Cytotoxicity of Nintedanib Exposure in Germ Cells of Mice: Quercetin from Onion Extracts Intervention”. EC Endocrinology and Metabolic Research 5.5 (2020): 04-18.

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