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Updated: Jul 2, 2025
Assessment of Chemical Toxicity in Adult Drosophila Melanogaster
Published on: March 24, 2023
Exposure to the Natural Compound Climacostol Induces Cell Damage and Oxidative Stress in the Fruit Fly Drosophila
Elisabetta Catalani1, Kashi Brunetti1, Simona Del Quondam1
1Department for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), Università degli Studi della Tuscia, 01100 Viterbo, Italy.
Abstract:
The ciliate Climacostomum virens produces the metabolite climacostol that displays antimicrobial activity and cytotoxicity on human and rodent tumor cells. Given its potential as a backbone in pharmacological studies, we used the fruit fly Drosophila melanogaster to evaluate how the xenobiotic climacostol affects biological systems in vivo at the organismal level. Food administration with climacostol demonstrated its harmful role during larvae developmental stages but not pupation. The midgut of eclosed larvae showed apoptosis and increased generation of reactive oxygen species (ROS), thus demonstrating gastrointestinal toxicity. Climacostol did not affect enteroendocrine cell proliferation, suggesting moderate damage that does not initiate the repairing program. The fact that climacostol increased brain ROS and inhibited the proliferation of neural cells revealed a systemic (neurotoxic) role of this harmful substance. In this line, we found lower expression of relevant antioxidant enzymes in the larvae and impaired mitochondrial activity. Adult offsprings presented no major alterations in survival and mobility, as well the absence of abnormal phenotypes. However, mitochondrial activity and oviposition behavior was somewhat affected, indicating the chronic toxicity of climacostol, which continues moderately until adult stages. These results revealed for the first time the detrimental role of ingested climacostol in a non-target multicellular organism.
Insights
The ciliate metabolite climacostol causes gastrointestinal and neurotoxic effects in fruit fly larvae, impacting development and cellular functions. While adult fruit flies show fewer effects, chronic toxicity indicates ongoing risks from this xenobiotic compound.
Area of Science:
- Pharmacology
- Toxicology
- Developmental Biology
Background:
- The ciliate *Climacostomum virens* produces climacostol, a metabolite with known antimicrobial and cytotoxic properties.
- Climacostol's potential pharmacological applications necessitate understanding its effects on non-target organisms.
- Investigating climacostol's in vivo toxicity is crucial for assessing its safety and broader biological impact.
Purpose of the Study:
- To evaluate the in vivo effects of the xenobiotic climacostol on the organismal level using *Drosophila melanogaster*.
- To determine the specific toxicological impacts of climacostol on various developmental stages and organ systems.
- To assess the systemic and chronic toxicity of climacostol.
Main Methods:
- Food administration of climacostol to *Drosophila melanogaster* larvae.
- Analysis of larval midgut and brain tissues for apoptosis and reactive oxygen species (ROS) generation.
- Assessment of enteroendocrine cell proliferation, antioxidant enzyme expression, mitochondrial activity, and adult phenotypes (survival, mobility, oviposition).
Main Results:
- Climacostol administration caused developmental toxicity in larvae, characterized by midgut apoptosis and increased ROS, indicating gastrointestinal toxicity.
- Systemic neurotoxicity was observed, with increased brain ROS and inhibited neural cell proliferation in larvae.
- While adult offspring showed no major survival or mobility defects, chronic toxicity was evident through affected mitochondrial activity and oviposition behavior.
Conclusions:
- Ingested climacostol exhibits detrimental gastrointestinal and neurotoxic effects in *Drosophila melanogaster* larvae.
- The xenobiotic substance demonstrates moderate damage without triggering repair mechanisms in the midgut.
- Chronic toxicity of climacostol persists into adulthood, affecting mitochondrial function and reproductive behavior, highlighting its impact on non-target multicellular organisms.
