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The alkyl chain length of 3-alkyl-3′,4′,5,7-tetrahydroxyflavones modulates effective inhibition of oxidative damage in biological systems: Illustration with LDL, red blood cells and human skin keratinocytes

2008; Elsevier BV; Volume: 77; Issue: 6 Linguagem: Inglês

10.1016/j.bcp.2008.11.023

1873-2968

Paulo Filipe, Artur M. S. Silva, Raquel S. G. R. Seixas, Diana C. G. A. Pinto, Álvaro da Silva Santos, L. K. Patterson, João Maia Silva, José A. S. Cavaleiro, João Freitas, Jean‐Claude Mazière, René Santús, Patrice Morlière,

Synthesis of Organic Compounds

It is shown that the relationship between the alkyl chain length of 3-alkyl-3',4',5,7 tetrahydroxyflavones (FnH) bearing alkyl chains of n=1, 4, 6, 10 carbons and their capacity to counter oxidative damage varies markedly with the nature of the biological system. In Cu(2+)-induced lipid peroxidation of low-density lipoprotein (LDL), the less hydrophobic short-chain F1H and F4H are probably located in the outer layer of LDL and parallel the reference flavonoid antioxidant, quercetin (Q) as effective inhibitors of lipid peroxidation. A marked inhibition of haemolysis induced in red blood cells (RBC) suspensions by the membrane-permeant oxidant, tert-butylhydroperoxide (t-BuOOH), is observed with F4H and F6H present at concentration in the micromolar range. However, F10H the most hydrophobic FnH is even more effective than Q against both haemolysis and lipid peroxidation as measured by malondialdehyde (MDA) equivalents. In oxidation of RBC by H(2)O(2,) at least 50 times more F6H and F10H than by t-BuOOH are required to only partly inhibit haemolysis and MDA production. The F1H, F4H and Q are found rather inactive under these conditions. At concentrations in the micromolar range, a marked protection against the cytotoxic effects of the t-BuOOH-induced oxidative stress in human skin NCTC 2544 keratinocytes is also exhibited by the four FnH antioxidants and is comparable to that of Q. Thus, the four FnH species under study may be considered as potent antioxidants which manifest complementary anti-oxidative actions in biological systems of markedly different complexity.