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.
Highlights
Reactive oxygen species (ROS) are chemical compounds formed upon incomplete oxygen reduction [1]
This study has described the application of cell membrane microarrays to determine the specific actions of antimalarial drugs on human tissues by monitoring the production of superoxide, one of the main reactive oxygen species (ROS), as indicator of celular stress
The experimental protocol was validated using cell membrane microarrays (CMMA) from a set of rat brain areas, whose stability and functionality has already been confirmed by different methods, together with specific inhibitors of the oxidative phosphorylation [53,54,55,56,57]
Summary
Reactive oxygen species (ROS) are chemical compounds formed upon incomplete oxygen reduction [1]. They are natural by-products of normal cellular activity and participate in cell signaling [2]. The disbalance between ROS production and the antioxidant defense system in the body causes the breakdown of cellular function and toxicity This may Membranes 2021, 11, 943 ipate in cell signaling [2]. This may occur due to an overproduction of ROS or a decrease in the antioxidant occur duemechanism
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