Creatine supplementation affords cytoprotection in oxidatively injured cultured mammalian cells via direct antioxidant activity

Free Radical Biology & Medicine
Piero SestiliVilberto Stocchi

Abstract

A growing body of evidence suggests that creatine (Cr) might exert protective effects in a variety of pathologies where oxidative stress plays a concausal etiologic role; furthermore, it has been recently reported that Cr displays direct antioxidant activity in a cell-free setting. However, at present, no research has been specifically aimed to directly test the antioxidant potential of Cr on oxidatively injured cultured cells. Here, the effects of Cr were studied using cultured human promonocytic (U937) and endothelial (HUVEC) cells, and murine myoblasts (C2C12) exposed to H(2)O(2), tert-butylhydroperoxide (tB-OOH) and, in the case of U937 cells, peroxynitrite. Cr (0.1-10 mM) attenuated the cytotoxic effects caused by the oxidants in all the cell lines; under our conditions, cytoprotection was invariably associated with elevation of the intracellular fraction of Cr but it seemed to be unrelated to the levels of Cr phosphate (CrP); Cr did not affect the activity of catalase (CAT) and glutathione peroxidase (GpX), but it prevented H(2)O(2)- or tB-OOH-induced consumption of the nonprotein sulfhydryl (NPSH) pool in U937 and HUVEC cells; mass spectrometry experiments showed that a 136 MW molecule, which is likely to represent an ox...Continue Reading

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