Indomethacin-induced gut damage in a surrogate insect model, Galleria mellonella

Abstract

Indomethacin is a non-steroidal anti-inflammatory drug that causes gastric ulceration and increased leakiness in rat models, and is used routinely as an assay to screen novel compounds for repair and restitution properties. We set out to establish conditions for indomethacin-induced gut damage in wax-moth (Galleria mellonella) larvae with a view to reducing the need for rodents in such experimentation. We administered indomethacin (1 - 7.5 g/larva) to G. mellonella via intrahaemocoelic injection and gavage (force-feeding) and monitored larval survival and development, blood cell (haemocyte) numbers, and changes in gut permeability. Increased levels of gut leakiness were observed within the first 4 to 24-hours by tracking fluorescent microspheres in the faeces and haemolymph (blood equivalent). Additionally, we recorded varying levels of tissue damage in histological sections of the insect midgut, including epithelial sloughing and cell necrosis. Degeneration of the midgut was accompanied by significant increases in detoxification-associated activities (superoxide dismutase and glutathione-S-transferase). Herein, we present the first evidence that G. mellonella larvae force-fed indomethacin display broad symptoms of gastric damage similar to rodent models.