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Updated: Jun 16, 2026
Cellular Redox Profiling Using High-content Microscopy
Published on: May 14, 2017
Study of Tissue-Specific Reactive Oxygen Species Formation by Cell Membrane Microarrays for the Characterization of
Ane Elexpe1,2, Nerea Nieto1,2, Claudia Fernández-Cuétara3
1Research and Development Division, IMG Pharma Biotech, 48160 Derio, Spain.
Abstract:
The production of reactive oxygen species (ROS) increases considerably in situations of cellular stress, inducing lipid peroxidation and multiple alterations in proteins and nucleic acids. However, sensitivity to oxidative damage varies between organs and tissues depending on the triggering process. Certain drugs used in the treatment of diverse diseases such as malaria have side effects similar to those produced by oxidative damage, although no specific study has been conducted. For this purpose, cell membrane microarrays were developed and the superoxide production evoked by the mitochondrial activity was assayed in the presence of specific inhibitors: rotenone, antimycin A and azide. Once the protocol was set up on cell membrane isolated from rat brain areas, the effect of six antimalarial drugs (atovaquone, quinidine, doxycycline, mefloquine, artemisinin, and tafenoquine) and two essential oils (Rosmarinus officinalis and Origanum majoricum) were evaluated in multiple human samples. The basal activity was different depending on the type of tissue, the liver, jejunum and adrenal gland being the ones with the highest amount of superoxide. The antimalarial drugs studied showed specific behavior according to the type of human tissue analyzed, with atovaquone and quinidine producing the highest percentage of superoxide formation, and doxycycline the lowest. In conclusion, the analysis of superoxide production evaluated in cell membranes of a collection of human tissues allowed for the characterization of the safety profile of these antimalarial drugs against toxicity mediated by oxidative stress.
Insights
This study investigated how antimalarial drugs affect superoxide production in human tissues. Certain drugs, like atovaquone and quinidine, increased superoxide, indicating potential oxidative stress risks.
Area of Science:
- Biochemistry
- Toxicology
- Pharmacology
Background:
- Cellular stress elevates reactive oxygen species (ROS), causing oxidative damage to lipids, proteins, and nucleic acids.
- Tissue sensitivity to oxidative damage varies, and some antimalarial drugs may induce similar side effects.
- No prior studies specifically linked antimalarial drug use to oxidative damage mechanisms.
Purpose of the Study:
- To develop and validate a cell membrane microarray assay for measuring superoxide production.
- To assess the oxidative stress potential of six antimalarial drugs and two essential oils in human tissues.
- To characterize the tissue-specific safety profiles of these antimalarial agents.
Main Methods:
- Developed cell membrane microarrays to assay mitochondrial superoxide production.
- Utilized specific inhibitors (rotenone, antimycin A, azide) to validate the protocol in rat brain tissue.
- Evaluated superoxide production in human tissue samples exposed to antimalarial drugs and essential oils.
Main Results:
- Basal superoxide production varied significantly across human tissues, with the liver, jejunum, and adrenal gland showing the highest levels.
- Antimalarial drugs exhibited distinct effects on superoxide production depending on the human tissue type.
- Atovaquone and quinidine significantly increased superoxide formation, while doxycycline showed the lowest impact.
Conclusions:
- Superoxide production assays in human cell membranes can characterize drug safety profiles.
- The study identified specific antimalarial drugs with varying potential to induce oxidative stress-related toxicity.
- Findings aid in understanding and mitigating the risks associated with antimalarial drug use.
