gms | German Medical Science

Background: Fucoidans from brown algae have a variety of positive biological effects for human health. Among other things, they can be protective against oxidative stress, anti-inflammatory and anti-tumorigenic. In this study, fucoidans from five different brown algae species were tested if and how they are protective against oxidative stress and iron-induced cell death (ferroptosis). With this biological model for subretinal bleeding, a possible application in ophthalmology can be evaluated.

Methods: Fucoidans were isolated from brown seaweed extracts of Fucus vesiculosus (FV1-3), Fucus serratus (FS), Fucus distichus subsp. evanescens (FE) with microwave-assisted extraction at 80° C and HCl as solvent, with the exception of FV1 and FV2, which were treated with ambient temperatures in HCl. Another fucoidan was isolated from a Laminaria hyperborea (LH) extract with hot-water extraction at 90° C. FV3, FS and FE were harvested at the same place and time. Three reference fucoidans, which are commercially available were used: FV from Sigma-Aldrich (FVs) as well as FV (FVm) and Undaria pinnatifida (UP) from Marinova. Test concentrations ranging from 1–50 µg/ml. Cell lines from uveal melanoma (OMM-1) and human RPE (ARPE-19) were used. Cell viability was determined with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Oxidative stress was induced with H2O2 and erastin. Cell number and morphology were examined, using an optical microscope, and vital cells were stained with calcein. Intracellular glutathione amount was assessed with GSH assay from Promega. Glutathione peroxidase 4 (GPX-4) expression was investigated with Western blot.

Results: FVm, FS, FE and LH lowered cell viability of OMM-1 cells (48 h), whereas FV2 lowered cell viability in ARPE-19 (24 h). FVm, UP, FS, FE, LH and FV2 showed protective effects against erastin in OMM-1 (48 h). FE, FS and LH were protective in ARPE-19 against erastin (24 h). No fucoidan showed protective effects against H2O2 in OMM-1 (48 h) and ARPE-19 (24 h). LH and FE increased the number of vital cells after erastin treatment (48 h) in OMM-1 cells, after calcein staining. LH increased GHS level in erastin treated ARPE-19 (3 h). LH also increased GSH level with and without erastin treatment in OMM-1 cells (3 h). FE and LH increased the GPX4 expression in OMM-1 cells after erastin induced stress (24 h). Because FV3, FS and FE were extracted and harvested equally, the differences in the biological effects in this study can be assumed to be dependent only on the algae species.

Summary: With this study, the antioxidative properties of fucoidans could be confirmed. But also, promising activities concerning protection against iron-dependent oxidative cell death could be shown. Some extracts even showed anti-tumorigenic activities. Extracts from FE, FS and LH seem promising concerning these activities, which are species-dependent. Possible pathways that are involved in the protective effects could be shown with the positive effects on GSH and GPX4. Also, the cell number and vitality could be increased as after inducing stress with erastin. Overall fucoidans from FE, FS and LH are interesting substances for a possible use against ocular diseases, in which oxidative stress and bleeding is involved.