Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Aims: Despite the presence of endogenous antioxidants in erythrocytes, these cells are highly susceptible to oxidative damage and some exogenous antioxidants, such as carotenoids, are able to inhibit the pro-oxidant effect provided by reactive oxygen species. In this study, we evaluated the potential of carotenoids usually detected in human blood plasma (beta-carotene, zeaxanthin, lutein, beta-cryptoxanthin and lycopene) to prevent the oxidative damage in erythrocytes. Main methods: Human erythrocytes were subjected to induced oxidative damage and the following biomarkers of oxidative stress were monitored: lipid peroxidation [induced by tert-butyl hydroperoxide (tBHP) or by 2,2'-azobis (2-methylpropionamidine) dihydrochloride (AAPH)] and AAPH-induced oxidation of hemoglobin and depletion of glutathione. Key findings: When tBHP was used to induce lipid peroxidation, lycopene was the most efficient carotenoid (IC50 = 2.2 +/- 0.4 mu M), while lutein was the most efficient (IC50 = 2.5 +/- 0.7 mu M) when peroxyl radicals (ROO center dot) were generated by AAPH. In relation to the hemoglobin oxidation induced by AAPH, beta-carotene and zeaxanthin were the most efficient antioxidants (IC50 = 2.9 +/- 0.3 mu M and 2.9 +/- 0.1 mu M, respectivelY). Surprisingly beta-cryptoxanthin and lycopene did not inhibit hemoglobin oxidation or lipid peroxidation when induced by AAPH, even at the highest tested concentration (3 mu M). Additionally, the tested carotenolds did not prevent ROO center dot-mediated GSH depletion and GSSG formation probably due to the lack of interaction between carotenoids (apolar) and glutathione (polar). Significance: Our study contributes with important insights that carotenoids may exert therapeutical potential to act as a natural antioxidant to prevent ROO center dot-induced toxicity in human erythrocytes. (C) 2014 Elsevier Inc. All rights reserved.99416715260Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao para a Ciencia e Tecnologia [SFRH/BPD/76909/2011]FSEMCTESFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [Proc. 2012/01356-0, 2013/07914-8]Fundacao para a Ciencia e Tecnologia [SFRH/BPD/76909/2011]