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Toxic potential of botulinum toxin type A on senescence in a Drosophila melanogaster model
Farnoosh Fooladvand1,2, Vida Tahouri1,2, Maryam Baeeri2
1Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.
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.
Insights
Botulinum toxin type-A (BoNT/A) at low doses activates aging pathways in Drosophila, but higher doses cause toxicity, including oxidative stress and DNA damage.
Area of Science:
- Toxicology
- Molecular Biology
- Aging Research
Background:
- Botulinum toxin type-A (BoNT/A) is widely used for neurological disorders.
- Potential side effects of BoNT/A necessitate further investigation.
- Understanding BoNT/A's impact on cellular aging is crucial.
Purpose of the Study:
- To investigate the dose-dependent effects of BoNT/A on aging in Drosophila melanogaster.
- To analyze molecular and phenotypic changes induced by BoNT/A exposure.
- To determine the threshold for BoNT/A-induced toxicity versus aging pathway activation.
Main Methods:
- Drosophila melanogaster larvae exposed to varying concentrations of BoNT/A (¼, ½, and LC50) and H2O2 (positive control).
- Molecular analyses included gene expression, comet assay, oxidative stress markers (ROS, SOD), and apoptosis markers (caspase-3, -9).
- Phenotypic changes, including body size and aging markers (β-gal, p16, p21, p38, p53), were assessed.
Main Results:
- BoNT/A induced dose-dependent cytotoxicity, increased ROS and SOD activity, and DNA damage.
- Apoptosis pathways (caspase-3, -9) were activated, and body size was reduced, particularly at higher doses.
- Low-dose BoNT/A up-regulated aging markers (β-gal, p16, p21, p38, p53), indicating aging pathway activation.
Conclusions:
- BoNT/A at low concentrations activates aging pathways in Drosophila.
- Higher BoNT/A doses lead to toxicity, characterized by oxidative stress, DNA damage, and apoptosis.
- The study highlights a dual effect of BoNT/A, with dose determining aging induction versus toxicity.
