| Summary: | Some antioxidant compounds decrease the amount of intracellular reactive oxygen species (ROS) and consequently reduce the deleterious effects of ROS in osteoblasts. Thus, these compounds fight against osteoporosis. Brown seaweeds are a rich source of antioxidant fucose-containing sulfated polysaccharides (fucans and fucoidans). We obtained six fucoidans (FRFs)—F0.3, F0.5, F0.7, F1.0, F1.5, and F2.1—from <i>Dictyota mertensii</i> by proteolytic digestion followed by sequential acetone precipitation. Except for F0.3, all FRFs showed antioxidant activity in different in vitro tests. In pre- osteoblast-like cells (MC3T3-L1) exposed to H<sub>2</sub>O<sub>2</sub>-oxidative stress, caspase-3 and caspase-9 were activated, resulting in apoptosis of the cells. We also observed a decrease in superoxide dismutase (SOD) and alkaline phosphatase (ALP) activity. The antioxidant FRFs protected the cells from the oxidative damage caused by H<sub>2</sub>O<sub>2</sub>, decreasing intracellular ROS and caspase activation, and increasing SOD activity. The most effective protection against damage was provided by F0.7, F1.5, and F2.1. At 0.5 mg/mL, these FRFs also suppressed the H<sub>2</sub>O<sub>2</sub>-mediated inhibition of ALP activity. The data indicated that FRFs F0.7, F1.5, and F2.1 from <i>D. mertensii</i> were antioxidants that protected bone tissue from oxidative stress and could represent possible adjuvants for the treatment of bone fragility through counteracting oxidative phenomena.
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