Toxic Potential of Botulinum Toxin Type a on Senescence in a Drosophila Melanogaster Model Publisher



Fooladvand F^{1, 2} ; Tahouri V^{1, 2} ; Baeeri M² ; Minaei T³ ; Rahimifard M² ; Hodjat M⁴ ; Khorasani R⁵ ; Haghiaminjan H⁶ ; Abdollahi M^{2, 5} Show Affiliations
Source: Toxicology Reports Published:2021

Abstract

Botulinum toxin type-A (BoNT/A) application, especially neurological disorders, has been spread nowadays while it may cause side effects. The current study aimed to assess the BoNT/A dose-dependent effect on induction of aging in the Drosophila melanogaster model. The third instar larvae of Drosophila melanogaster were exposed to ¼ LC50, ½ LC50, and LC50 of BoNT/A in the Drosophila diet for 48 h while H2O2 1% was used as a positive control. After the exposure time, some larvae were collected for molecular study, including gene expression analysis, comet assay, oxidative stress markers, and the phenotype changes. BoNT/A induced dose-dependent cytotoxicity, elevated reactive oxygen species (ROS) levels, and superoxide dismutase (SOD) enzyme activity. In addition, it caused DNA damage and activated caspase-3 and -9, and reduced the body size of the fly, especially in high doses. In line with the purpose of the study, aging markers, including β-galactosidase (β-gal), p16, p21, p38, and p53, were up-regulated by BoNT/A low dose. BoNT/A activates the aging pathway in the low dose, and increasing the dose induces toxicity, including oxidative stress, DNA damage, and apoptosis. © 2021 The Author(s)