e-journal

Preliminary safety evaluation of a taurocholateconjugated low-molecular-weight heparin derivative (LHT7): a potent angiogenesis inhibitor

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In our previous studies, taurocholic acid (TA)-conjugated low-molecular-weight heparin derivative (LHT7) has
been proven to be a potent anti-angiogenic agent by demonstrated successful blockage capability of vascular endothelial
growth factors (VEGF). Preliminary safety evaluations were conducted based on its mechanism of action and chemical
behavior. For this purpose, acute toxicity study, and hematological and serological evaluations were carried out. Additionally,in order to evaluate mechanism-related side effects, both blood pressure and the occurrence of proteinuria were measured using a treatment regime of multiple high doses of LHT7 in a biodistribution study. LD50 values for LHT7 in female and male mice were 56.9 and 64.7 mg kg–1 doses, respectively. There were no vital fluctuations in the serological and hematological parameters, except for the elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at 100 and 200 mg kg–1 doses of LHT7, representing vital changes in the liver function. Moreover, the results of mechanism-related studies showed that blood pressure at 50 mg kg–1 did not change but showed elevated levels of protein in urine. In the biodistribution study, a slight accumulation of LHT7 in the kidney and the liver were observed at the 50 mg kg–1 repeated dose owing to the presence of bile acid. No fatal damage was observed in this study; most observations were related to the chemical composition or the mechanism of action of the material. Copyright © 2014 John Wiley & Sons, Ltd.

Keywords: low-molecular-weight heparin; taurocholate; angiogenesis inhibitor; vascular endothelial growth factors; preclinical study

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Informasi Detail

Judul Seri

J. Appl. Toxicol.

No. Panggil

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Penerbit

: John Wiley & Sons, Ltd.., 2015

Deskripsi Fisik

J. Appl. Toxicol. 2015; 35: 104–115

Bahasa

English

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Klasifikasi

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Tipe Isi

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Tipe Media

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Tipe Pembawa

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Edisi

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Subjek

FISIKA

Info Detail Spesifik

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Pernyataan Tanggungjawab

Wati/Agus

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