As one of the many edible brown algae, Laminaria japonica has seen increased productivity through recent breeding efforts designed to improve commercial cultivation. Fucoidan extracted from Laminaria japonica has been studied for its diverse biological activities. However, brown algae accumulate arsenic (As) during growth, their total arsenic content is relatively higher than that of green and red algae, and organic arsenic may be a carcinogenic promoter.

So, in this blog, I would like to share the following study, “Toxicological Evaluation of Low Molecular Weight Fucoidan in Vitro and in Vivo” by Pai-An Hwang et al. A study using 25 six-week-old male ICR mice confirmed the toxicity of low molecular weight fucoidan (LMF) extracted from Laminaria japonica via enzymatic hydrolysis. Toxicity was assessed via total arsenic content, bacterial reverse mutation test, chromosomal aberration test, and in vivo micronucleus test.

First, they investigated the total arsenic content and arsenic species in raw L. japonica and LMF. Arsenic (As) compounds in brown algae include major organic forms such as monomethylarsonic acid (MMA), dimethararsinic acid (DMA), arsenobetaine (AsB), and arsenocholine (AsC), which are significantly less toxic than inorganic forms such as arsenate (AsIII) and arsenate (AsV), but organic arsenics may promote carcinogenesis. Therefore, we investigated the total arsenic content and arsenic species in raw L. japonica and LMF. The total arsenic in L. japonica was 61.100 ± 3.110 mg/kg, and the LC-ICP-MS results showed that the concentrations of arsenic species in L. japonica were as follows: AsB (34.31 ± 1.21 mg/kg) > MMA (9.27 ± 0.96 mg/kg) > DMA (9.23 ± 0.83 mg/kg) > AsC (59.00 ± 1.65 mg/kg). AsIII and AsV species were not detected. The total arsenic in LMF-LJ was 6.200 ± 2.005 mg/kg, and AsIII and AsV were not detected. No inorganic arsenic was detected in L. japonica and LMF-LJ.

A bacterial reverse mutation test was conducted to evaluate the genotoxicity of LMF-LJ and see if it induced DNA mutations in the test organisms. No dose-dependent effect on revertant colonies was observed up to LMF-LJ concentrations of 5000 μg/mL. LMF-LJ did not increase revertant colonies per plate by more than twofold compared to the negative control, irrespective of S9 metabolic activation. The positive controls for each strain showed a significant increase in the number of revertant colonies, as expected. The data showed no evidence of the mutagenic potential of LMF-LJ under the conditions used in this study.

Scientists used a chromosomal aberration test to assess the mutagenic potential of the LMF-LJ gene. The highest dose tested in the chromosomal aberration test was 5000 μg/mL. No increase in structural or numerical chromosomal aberrations was observed at any dose of LMF-LJ (312.5–5000 μg/mL) compared to the negative control, with or without S9. The positive control MMC, with or without S9, increased the frequency of cells showing more than 10% chromosomal aberrations. Thus, LMF-LJ, like LMF in U. pinnatifida, does not induce chromosomal aberrations according to the present study.

In summary, the findings of this study indicate that LMF-LJ did not exhibit mutagenic properties at a concentration of 5000 μg/mL, based on the negative results observed in both bacterial reverse mutation and in vitro chromosomal aberration tests. The in vivo experiments conducted revealed that LMF-LJ had no impact on the process of erythrocyte formation. Repeated oral administration to SD rats for 28 days showed no signs of toxicity even when LMF-LJ was administered up to 2000 mg/kg BW/day. Given the expectation of safety with LMF-LJ, we can expect LMF to be used safely as a food supplement.

Source: Mar Drugs. 2016 Jun 24;14(7):121. doi: 10.3390/md14070121