Antagonistic effects of chemical mixtures on the oxidative stress response are silenced by heat stress and reversed under dietary restriction
Chemical agents released into the environment can induce oxidative stress in organisms, which is detrimental for health and has been linked to neurodegenerative diseases. C. elegans has been important as model organism to understand oxidative stress caused by chemical agents. In this work, we explore how chemical mixtures drive the oxidative stress response under various conditions. Our results indicate that mixtures drive responses differently than individual components, and that altering environmental conditions, such as increased heat and reduced food availability, result in dramatically different oxidative stress responses mounted by C. elegans. When exposed to heat, the oxidative stress response is diminished. Notably, when exposed to limited food, the oxidative stress response to juglone is significantly heightened, while interactions between some naphthoquinones components in mixtures cease to be antagonistic. This suggests that organismal responses depend on the environment and stressor interactions. Given the high number of variables under study, and their potential combinations, a simplex centroid design was used to capture such non-trivial response over the design space. This makes the case for the adoption of Design of Experiments approaches as they can greatly expand the experimental space probed in noisy biological readouts. Our results also reveal gaps in our current knowledge of the stress response, which can be addressed by employing sophisticated design of experiments approaches to identify significant interactions.