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Author Kang, Shin-Ae ♦ Tsolmon, Bilegtsaikhan ♦ Mann, Aman P. ♦ Zheng, Wei ♦ Zhao, Lichao ♦ Zhao, Yan Daniel ♦ Volk, David E. ♦ Lokesh, Ganesh L. -R. ♦ Morris, Lynsie ♦ Gupta, Vineet ♦ Razaq, Wajeeha ♦ Rui, Hallgeir ♦ Suh, K. Stephen ♦ Gorenstein, David G. ♦ Tanaka, Takemi
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ DOSES ♦ INTRAVENOUS INJECTION ♦ LIVER ♦ LYMPHOKINES ♦ MAMMARY GLANDS ♦ METASTASES ♦ MICE ♦ NEOPLASMS ♦ SAFETY ANALYSIS ♦ TOXICITY
Abstract The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100 μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500 μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions. - Highlights: • Intravenous administration of ESTA was well tolerated. • ESTA up to 500 μg does not cause hematologic, organs, and immunologic responses. • ESTA-mediated hepatic abnormality was considered minor.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-08-15
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 287
Issue Number 1


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