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To emphasize the importance of the oxidative stress as the main mechanism of pravastatin side effect, we supplemented mice diet with another mevalonate pathway independent antioxidant, creatine, which was recently shown to protect against muscle mitochondrial oxidative damage induced by pravastatin ( Figures 2E,F show that creatine diet supplementation also significantly decreased H 2 O 2 production and restored aconitase activity that were altered by pravastatin treatment ( Figure 3 )

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Rodent studies Eight preclinical studies investigated the effect of supplementation with a combination of different nutrients on ES-induced behavioral deficits, out of which six studies found an effect of ES on at least one of the behavioral domains investigated and those will be described below

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