Abstract
Indomethacin is a non-steroidal anti-inflammatory drug that causes gastric ulceration and increased ‘leakiness’ in rat models, and is used routinely as a toxicology 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 (0.5–7.5 µg/larva; 2–30 mg/kg) to G. mellonella via intrahaemocoelic injection and gavage (force-feeding) and monitored 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 h 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 their rodent counterparts.
Highlights
When considering more carefully our use of vertebrates in disease and toxicology experimentation, there is constant need to develop alternative model systems in vitro, in vivo or in silico
G. mellonella have been used to study the infectivity of gut pathogens such as Campylobacter jejuni (Senior et al 2011), Listeria monocytogenes (Mukherjee et al 2013a), Vibrio spp. (Wagley et al 2018), Shigella spp. (Barnoy et al 2017) and Salmonella enterica (Card et al 2016), there remains a distinct lack of information regarding the alimentary canal of this insect and its role in pathogenesis
Intrahaemocoelic injection of indomethacin had no measurable negative impacts on larval survival across the concentration range 0.5–7.5 μg/larva (0% mortality), which is the equivalent to 2–30 mg/kg in rodents
Summary
When considering more carefully our use of vertebrates in disease and toxicology experimentation, there is constant need to develop alternative model systems in vitro, in vivo or in silico. One such in vivo alternative is the larvae of the greater wax-moth, Galleria mellonella. These insects are used widespread as ‘mini-hosts’ for the investigation of microbial pathogenicity (Mowlds et al 2010; Kloezen et al 2015; Lim et al 2018; Cools et al 2019), screening of xenobiotics/toxins (Allegra et al 2018; Coates et al 2019) and functional. G. mellonella have been used to study the infectivity of gut pathogens such as Campylobacter jejuni (Senior et al 2011), Listeria monocytogenes (Mukherjee et al 2013a), Vibrio spp. (Wagley et al 2018), Shigella spp. (Barnoy et al 2017) and Salmonella enterica (Card et al 2016), there remains a distinct lack of information regarding the alimentary canal of this insect and its role in pathogenesis
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