A fruit fly-based approach to unraveling enteropathy-causing pharmaceuticals

Area of Science:

• Pharmacology
• Toxicology
• Genetics

Background:

• Enteropathy, a small intestine disorder, can be caused by drugs like non-steroidal anti-inflammatory drugs (NSAIDs).
• Preclinical drug testing often uses rodents, which present ethical concerns and high costs.
• Alternative models like *Drosophila melanogaster* offer a cost-effective, ethically sound in vivo platform with genetic relevance.

Purpose of the Study:

• To assess *Drosophila melanogaster* as an in vivo model for evaluating drug-induced enteropathy.
• To investigate the molecular effects of indomethacin, an NSAID, on fruit flies.

Main Methods:

• *Drosophila melanogaster* were treated with varying concentrations of indomethacin.
• Survival and intestinal integrity (Smurf assay) were monitored.
• Gene expression analysis (RT-qPCR) was performed for inflammatory, mitochondrial, and antioxidant markers.

Main Results:

• Indomethacin did not affect fruit fly lifespan or cause observable intestinal damage.
• Pro-inflammatory cytokine gene expression (drs, totA) increased significantly.
• Upregulation of mitochondrial stability (tom40) and antioxidant genes (sod1, sod2, cat) was observed, particularly at higher indomethacin concentrations.

Conclusions:

• *Drosophila melanogaster* demonstrates molecular signs of inflammation in response to indomethacin, despite a lack of phenotypical gut damage.
• The fruit fly serves as a viable model for detecting early-stage, molecular-level drug side effects like enteropathy.