Cytoprotective effects of short-term treatment with grape seed extract (GSE) upon human gingival fibroblasts (hGFs) were evaluated in relation to its antioxidant properties and compared with those of a water-soluble analog of vitamin E: trolox (Tx). GSE and Tx showed comparable antioxidant potential in vitro against di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH; a stable radical), hydroxyl radical (·OH), singlet oxygen ( O ), and hydrogen peroxide (H O ). Pretreatment or concomitant treatment with GSE for 1 min protected hGFs from oxidative stressors, including H O , acid-electrolyzed water (AEW), and O , and attenuated the intracellular formation of reactive oxygen species induced by H2O2 and AEW. Tx also reduced the H O - and AEW-induced intracellular formation of reactive oxygen species, but showed no cytoprotective effects on hGFs exposed to H O , AEW, or O . These results suggest that the cytoprotective effects of GSE are likely exerted independently of its antioxidant potential. Copyright: 1 1 1 2 2 2 2 2 2 2 2 2 2 2