Single Oral Dose Toxicity Test of Low Molecular Weight Fucoidan in Rats

Yoon, Hyun-Soo; Shin, Yong‐Kyu; Jung, Youngmi; Lee, Hyeung-Sik; Ku, Sae‐Kwang

doi:10.4062/biomolther.2009.17.3.325

Cited by 11 publications

(8 citation statements)

References 20 publications

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“…However, we also found that its molecular weight was 1288.81 ± 62.55 kDa, which indicates a high molecular weight. In 2009, Yoon showed that fucoidan can be divided into low (< 10 kDa), medium (10–10,000 kDa) and high (> 10,000 kDa) molecular weights [ 33 ]. This molecular weight falls within the range of (10–10,000 kDa) mid-molecular-weight fucoidan [ 34 ], and low-molecular-weight fucoidan has better biological activity and it is easier to develop into anticancer drugs [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

Fucoidan with three functions extracted from Sargassum aquifolium integrated rice-husk synthesis dual-imaging mesoporous silica nanoparticle

Lee

Chen

et al. 2022

J Nanobiotechnol

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In this study, we used the nanoparticle delivery system to reduce the side effect of conventional cancer treatment- radiation therapy and chemotherapy. We used rice husk silicon source mesoporous silica nanoparticle doped in Eu3+ and Gd3+ as the carrier in the delivery system and to enable fluorescence and MRI dual-imaging functions for follow-up therapy. In addition, we choose a popular seaweed extract—fucoidan was extracted from the same brown algae—Sargassum aquifolium collected from Taiwan-Pingtung-Kenting-Chuanfan Rock. In this research, we used acid hydrolysis to prepared two different molecular weight fucoidan, the small molecular fucoidan (Fus) as drug, and the molecular weight approximately 1 kDa fucoidan (Ful) as the nanoparticle gatekeeper, and as targeting molecule for overexpressed P-selectin on the surface of the metastatic tumors. The results of the cell cytotoxicity experiment showed that HCT116 cancer cells have a survival rate of approximately 58.12% when treated with 200 μg/mL fucoidan. Dual-imaging rice husk mesoporous silica nanoparticles (rMSN-EuGd) were modified with 1 kDa fucoidan (Ful) as the gatekeeper and target, and the small molecule fucoidan (Fus) was loaded into nanoparticles (Ful-Fus@rMSN-EuGd) at a concentration of 200 μg/mL. The HCT116 cancer cells had a survival rate of approximately 55.56%. The cell cytotoxicity experiment results show that Ful-Fus@rMSN-EuGd can improve the anticancer effect of fucoidan, and the nanoparticle drug delivery system using fucoidan as a drug, target, and gatekeeper was successfully synthesized.

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Section: Resultsmentioning

confidence: 99%

Fucoidan with three functions extracted from Sargassum aquifolium integrated rice-husk synthesis dual-imaging mesoporous silica nanoparticle

Lee

Chen

et al. 2022

J Nanobiotechnol

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“…Especially, the edematous changes in uterus were considered as secondary changes from different physiological estrus cycles (32 , 33) . In addition, most of them were also rarely but generally observed as sporadic accidental findings in rodent toxicity studies (5 , 23 , 24) .…”

Section: Discussionmentioning

confidence: 99%

“…Statistical analyses were conducted using SPSS for Windows (Release 14.0K, SPSS Inc., USA) and a p -value of less than 0.05 was considered to be a significant difference. In addition, degree of clinical signs, gross and histopathological findings were subdivided into 3 degrees: 3+ Severe, 2+ moderate, 1+ slight, according to the previous reports (5 , 23 , 24) .…”

Section: Methodsmentioning

confidence: 99%

Single Oral Dose Toxicity Study of Prebrewed Armeniacae Semen in Rats

Park¹,

Seo²,

Cho³

et al. 2013

Toxicological Research

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Armeniacae semen (AS) has been considered a toxic herb in the Korean medicine as it contains hydrogen cyanide and amygdalin, especially in its endocarp. Therefore, prebrewed AS that is devoid of endocarp has been traditionally used. In the present study, amygdalin content of the prebrewed AS was significantly lower (2.73 ± 0.32 μg/ml; p < 0.01) than the content in the extract that contained the endocarps (28.50 ± 6.71 μg/ml); amygdalin content corresponded to 10% of the extract in the present study. Because of single oral dose toxicity of prebrewed AS according to the recommendation of Korea Food and Drug Administration Guidelines (2009-116, 2009), which was based on single oral dose toxicity study of prebrewed AS, mortality due to toxic principles was significantly reduced. In this study, 2,000 mg/kg of prebrewed AS led to death of 1 female rat and 1 male rat at the end of 2 hr of administration. Based on these results, the 50% lethal dose in both male and female rats was determined to be 9279.5 mg/kg. Seizure, loss of locomotion, and increases in respiration and heart rate were observed as prebrewed AS treatment-related toxicological signs; these signs were restrictedly manifested in the prebrewed AS (2,000 mg/kg)-treated rats. In addition, no changes were observed in body weight, organ weight, gross features, and histopathological parameters with 2,000 mg/kg of AS in both male and female rats. These findings serve as direct evidence that amygdalin in AS is the toxic principle, which can be reduced by the traditional prebrewing method involving the exclusion of endocarp.

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“…In the present study, the dosage volume was selected as 10 ml/kg, the recommended oral dose volume in rat (Flecknell, 1996) and the highest dosages, 2,000 mg/kg was selected based on the results of rat single dose toxicity test (Yoon et al, 2009), in which no noticeable toxicities were detected up to 2,000 mg/kg of dose levels in the both female and male rats, and 1,000 and 500 mg/kg were selected as middle and low dosages using common ratio 2 according to KFDA Guidelines (2005). In addition each female and male vehicle controls were added.…”

Section: Discussionmentioning

confidence: 99%

“…Although preclinical studies using HMF have been performed (Li et al, 2005); up to now, no detailed toxicological assessment of LMF has been reported except for mouse and rat single oral dose toxicity (Jung et al, 2008;Yoon et al, 2009). Therefore, the primary safety information after 14-day repeat oral treatment of LMF, obtained by acid hydrolysis of HMF from brown seaweed according to a previously published protocol (Nardella et al, 2000;Jung et al, 2007) were evaluated using rats, to determine the highest dosage for further 4-week repeated dose toxicity test and further clarity their safety for clinical use.…”

Section: Introductionmentioning

confidence: 99%

14 Days Repeat Oral Dose Toxicity of Low Molecular Weight Fucoidan in Rats

Yoon¹,

Shin²,

Lee³

et al. 2010

Biomolecules and Therapeutics

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-In order to investigate the preliminary repeat oral dose toxicity and to determine the highest dosage for further 4-week repeated dose toxicity test, Low Molecular Weight Fucoidan (LMF) has been showed various pharmacological effects, was orally administered to female and male rats, once a day for 14 days at dose levels of 2,000, 1,000, 500 and 0 (vehicle control) mg/kg (body weights) in a volume of 10 ml/kg. The mortality and changes on the body weights, clinical signs, hematology, serum biochemistry and gross observations were monitored with organ weight and histopathology of principle organs. As the results of 14-day repeated oral treatment of LMF, no LMF treatment related mortalities were detected up to 2,000 mg/kg in both male and female rats, respectively. In addition, no noticeable changes on the body weight and clinical signs were detected except for significant decreases on the body weights and gains restricted to male 2,000 mg/kg treated groups as compared with male vehicle control. No meaningful changes on the organ weights, hematological, serum biochemistrical, gross and histopathological findings were observed. Therefore the highest dosage in the 4-week repeated dose toxicity test is suggested as 2,000 mg/kg in both female and male rats, respectively.

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Single Oral Dose Toxicity Test of Low Molecular Weight Fucoidan in Rats

Cited by 11 publications

References 20 publications

Fucoidan with three functions extracted from Sargassum aquifolium integrated rice-husk synthesis dual-imaging mesoporous silica nanoparticle

Fucoidan with three functions extracted from Sargassum aquifolium integrated rice-husk synthesis dual-imaging mesoporous silica nanoparticle

Single Oral Dose Toxicity Study of Prebrewed Armeniacae Semen in Rats

14 Days Repeat Oral Dose Toxicity of Low Molecular Weight Fucoidan in Rats

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