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Rotenone is known to be a potent inhibitor of complex I of the mitochondrial respiratory chain in all cell types, by inhibiting the function of mitochondrial NADH dehydrogenase activity (Sherer et al ., 2003

Schmidt, K., Noureen, A., Kronenberg, F., & Utermann, G

Age-related increases in oxidative stress have been associated with chronic inflammation, cardiovascular and neurodegenerative disease, osteoarthritis and type 2 diabetes in humans (Reference Cannizzo, Clement and Sahu4Reference Rains and Jain6) and companion animals, namely cats (Reference Brown7,Reference Vite and Head8) and dogs (Reference Brown7Reference Pizzirani10)

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Through co-encapsulation, such nanoparticles could release BBB modulators in the local tumor site, which adjust the permeability of BBB in the paracellular pathway to ensure more nanoparticles in the same area