Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice. Toxicol Appl Pharmacol 2015 Aug 15;287(1):86-92
Date
06/07/2015Pubmed ID
26048585Pubmed Central ID
PMC4966538DOI
10.1016/j.taap.2015.05.011Scopus ID
2-s2.0-84935867738 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
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 100μg 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 500μg 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.
Author List
Kang SA, Tsolmon B, Mann AP, Zheng W, Zhao L, Zhao YD, Volk DE, Lokesh GL, Morris L, Gupta V, Razaq W, Rui H, Suh KS, Gorenstein DG, Tanaka TMESH terms used to index this publication - Major topics in bold
Alanine TransaminaseAnimals
Antineoplastic Agents
Aptamers, Nucleotide
Aspartate Aminotransferases
Biomarkers
Chemical and Drug Induced Liver Injury
Complement C3a
Complement C5a
Cytokines
Dose-Response Relationship, Drug
Drug Administration Schedule
E-Selectin
Female
Injections, Intravenous
Kidney
Liver
Male
Mice, Inbred ICR
Necrosis
Risk Assessment
