Galleria mellonella as a drug discovery model to study oxidative stress
Fred Jonathan Edzeamey1, Zenouska Ramchunder1, Ronan R McCarthy1
1Department of Biosciences, College of Health, Medicine and Life Sciences, Brunel University of London, London, UK.
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.
Insights
Galleria mellonella larvae serve as a novel in vivo model for oxidative toxicity studies. Resveratrol and Alpha tocopherol protected larvae from oxidative stress, demonstrating their therapeutic potential.
Area of Science:
- Biochemistry
- Toxicology
- Invertebrate models
Background:
- Biological systems possess antioxidant defenses against reactive oxygen species (ROS).
- ROS accumulation causes oxidative toxicity, implicated in neurodegenerative diseases, cancer, and diabetes mellitus.
- Establishing robust in vivo models for oxidative toxicity research remains a challenge.
Purpose of the Study:
- To validate Galleria mellonella larvae as an effective in vivo model for oxidative toxicity research.
- To assess the in vivo toxicity and in vitro cell viability of various antioxidant compounds.
- To evaluate the protective effects of selected antioxidants against induced oxidative stress.
Main Methods:
- Determined tolerable concentrations of eight antioxidant compounds in Galleria mellonella larvae.
- Assessed compound toxicity in primary human fibroblast cell lines in vitro.
- Investigated the rescue efficacy of Resveratrol and Alpha tocopherol against juglone-induced oxidative toxicity in larvae.
Main Results:
- Alpha tocopherol and Orotic acid showed no toxicity in larvae; other compounds exhibited toxicity.
- Tolerable larval concentrations of compounds resulted in 50-100% cell viability in vitro.
- Resveratrol and Alpha tocopherol demonstrated significant protective effects against juglone-induced oxidative stress in larvae.
Conclusions:
- Galleria mellonella larvae are suitable for oxidative toxicity screening and proof-of-concept studies.
- This model facilitates preliminary assessment of antioxidant compounds before in vitro and in vivo therapeutic evaluations.
- The study highlights the potential of specific antioxidants in mitigating oxidative damage.
