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Antagonistic effects of chemical mixtures on the oxidative stress response are silenced by heat stress and reversed under dietary restriction

Karthik Suresh Arulalan, Javier Huayta, Jonathan W. Stallrich, View ORCID ProfileAdriana San-Miguel
doi: https://doi.org/10.1101/2021.03.17.435857
Karthik Suresh Arulalan
1Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, USA
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Javier Huayta
1Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, USA
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Jonathan W. Stallrich
2Department of Statistics, North Carolina State University, Raleigh, North Carolina, USA
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Adriana San-Miguel
1Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, USA
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  • ORCID record for Adriana San-Miguel
  • For correspondence: asanmiguel@ncsu.edu
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Abstract

Chemical agents released into the environment can induce oxidative stress in organisms, which is detrimental for health. Although environmental exposures typically incorporate multiple chemicals, organismal studies on oxidative stress derived from chemical agents commonly study exposures to individual compounds. In this work, we explore how chemical mixtures drive the oxidative stress response under various conditions in the nematode C. elegans, by quantitatively assessing levels of gst-4 expression. Our results indicate that naphthoquinone 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 specific to juglone is significantly heightened, while identified antagonistic interactions between some naphthoquinone components in mixtures are abolished. This implies that organismal responses to xenobiotics is confounded by 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, and in combinatorial experiments. Our results also reveal gaps in our current knowledge of the organismal oxidative stress response, which can be addressed by employing sophisticated design of experiments approaches to identify significant interactions.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 04, 2021.
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Antagonistic effects of chemical mixtures on the oxidative stress response are silenced by heat stress and reversed under dietary restriction
Karthik Suresh Arulalan, Javier Huayta, Jonathan W. Stallrich, Adriana San-Miguel
bioRxiv 2021.03.17.435857; doi: https://doi.org/10.1101/2021.03.17.435857
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Antagonistic effects of chemical mixtures on the oxidative stress response are silenced by heat stress and reversed under dietary restriction
Karthik Suresh Arulalan, Javier Huayta, Jonathan W. Stallrich, Adriana San-Miguel
bioRxiv 2021.03.17.435857; doi: https://doi.org/10.1101/2021.03.17.435857

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