Sertraline induces DNA damage and cellular toxicity in Drosophila that can be ameliorated by antioxidants

Abstract

Sertraline hydrochloride is a commonly prescribed antidepressant medication that acts by amplifying serotonin signaling. Numerous studies have suggested that children of women taking sertraline during pregnancy have an increased risk of developmental defects. Resolving the degree of risk for human fetuses requires comprehensive knowledge of the pathways affected by this drug. We utilized a Drosophila melanogaster model system to assess the effects of sertraline throughout development. Ingestion of sertraline by females did not affect their fecundity or embryogenesis in their progeny. However, larvae that consumed sertraline experienced delayed developmental progression and reduced survival at all stages of development. Genetic experiments showed that these effects were mostly independent of aberrant extracellular serotonin levels. Using an ex vivo imaginal disc culture system, we showed that mitotically active sertraline-treated tissues accumulate DNA double-strand breaks and undergo apoptosis at increased frequencies. Remarkably, the sertraline-induced genotoxicity was partially rescued by co-incubation with ascorbic acid, suggesting that sertraline induces oxidative DNA damage. These findings may have implications for the biomedicine of sertraline-induced birth defects.

Determination of the Effect of Wastewater on the Biological Activity of Mixtures of Fluoxetine and Its Metabolite Norfluoxetine with Nalidixic and Caffeic Acids with Use of E. coli Microbial Bioindicator Strains

“…The results obtained in our study indicate that oxidative stress may be one of the main toxicity mechanisms of FLU, Nor-FLU, NA and their mixtures. Our results are in agreement with those of other authors, where it was noticed that SSRIs, including FLU, have a toxic and genotoxic effect and have the potential to generate oxidative stress as the main mechanism, leading to the permanent damage of cells exposed to these drugs [44]. The potential for generating oxidative stress in cells exposed to FLU has also been described in other works.…”

Studying the Liver Function in Male Neonates of Rats Born to Sertraline-Treated Mothers

“…The studies represent that Sertraline consumption during pregnancy is associated with shortterm and long-term adverse effects in children (Shen et al 2017). Other studies also indicate that Sertraline can induce oxidative DNA damage and increase the level of cellular apoptosis (Jajoo et al 2020). The studies suggest that Sertraline has teratogenic and toxic effects on the fetus.…”

Attenuation of Seizures, Cognitive Deficits, and Brain Histopathology by Phytochemicals of Imperata cylindrica (L.) P. Beauv (Poaceae) in Acute and Chronic Mutant Drosophila melanogaster Epilepsy Models

“…115 In addition, attenuation and rescue of neurological defects by natural antioxidants have been reported in Drosophila models of epilepsy 143 and Drosophila is an emerging model organism for plant-derived antioxidants. [147][148][149] Most importantly, the potential role of natural antioxidants from plant extracts as neuroprotectants for treating and preventing neurodegenerative diseases and epilepsy has been shown in vitro, in vivo, and in clinical settings. 89,137,150 In addition, hyperactivity of the VGCs due to mutation (s) in the para gene (gain-of-function mutation in the para sodium channel gene at the para locus) in neuronal brain tissues of bang-sensitive (BS) Drosophila models of epilepsy is strongly linked to the neuropathological features of epilepsy (brain histopathology, seizures, and cognitive deficits).…”