Galleria mellonella as a drug discovery model to study oxidative stress

Abstract

Biological systems are equipped with endogenous antioxidant defence mechanisms against reactive oxygen species (ROS). Accumulation of ROS usually overwhelms this, creating pathologic effects. Oxidative toxicity has been reported as a causative factor in neurodegenerative diseases, cancer and diabetes mellitus (DM). However, developing an elaborate in vivo model system for mechanistic and therapeutic studies has been challenging. This present study sought to establish Galleria mellonella larvae as an ideal model for studying oxidative toxicity as a precursor to in vitro studies. We investigated Indole-3-propionic acid, Trolox, Resveratrol, Alpha tocopherol, Alpha lipoic acid, Orotic acid, Ginsenoside RB1, and Xanthohumol in this study, based on their antioxidant effects previously reported in different disease models. Tolerable concentrations of the compounds were established in vivo. Whilst no toxicity was recorded following treatment with Alpha tocopherol and Orotic acid, the remaining compounds displayed marked toxicity. We then conducted cell viability experiments in primary human fibroblast cell lines, and observed that tolerable concentrations in larvae produced 50–100% cell viability in vitro. Finally, Resveratrol and Alpha tocopherol were observed to rescue the larvae from juglone-induced oxidative toxicity. The larvae of Galleria mellonella can therefore be used for conducting oxidative toxicity and proof-of-concept studies of compounds.