PMID: 9450915Feb 5, 1998Paper

Toxicologic effects of an oligodeoxynucleotide phosphorothioate and its analogs following intravenous administration in rats

Antisense & Nucleic Acid Drug Development
S AgrawalD Serota

Abstract

The aim of the present study is to evaluate the in vivo toxicologic effects of a phosphorothioate oligodeoxynucleotide (PS oligo) and three of its analogs [PS oligo containing four methylphosphonate linkages at the 3' and 5'-ends (MBO 1), PS oligo containing four 2'-O-methylribonucleosides at both the 3'- and 5'-ends (MBO 2), and PS oligo containing an 8 bp loop region at the 3'-end (self-stabilized oligo)]. Oligodeoxynucleotides were administrated intravenously to male and female rats at doses of 3, 10, and 30 mg/kg/day for 14 days. Rats were killed on day 15, blood samples were collected for hematology and clinical chemistry determinations, and tissues, including lymph nodes, spleens, livers, and kidneys, were subjected to pathologic examinations. The toxicity profiles of the four oligodeoxynucleotides were very similar, but differed in magnitude. In terms of the severity of the abnormalities caused by the oligodeoxynucleotides, the order was MBO 2 > PS oligo > self-stabilized oligo > MBO 1. Alterations in hematology parameters included thrombocytopenia, anemia, and neutropenia. Abnormalities in clinical chemistry parameters observed with PS oligo or MBO 2 were dose-dependent elevation of liver transaminases and reduction of ...Continue Reading

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Citations

Oct 5, 2010·Cancer Chemotherapy and Pharmacology·Eckhardt S FerdinandiAiping H Young
Jun 9, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Gabor LendvaiAnne Roivainen
Apr 18, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·F WuB Långström
Feb 5, 2000·Bioorganic & Medicinal Chemistry·Z JiangS Agrawal
Feb 1, 2000·Molecular Medicine Today·S Agrawal, E R Kandimalla
Sep 16, 1998·Current Opinion in Chemical Biology·S Agrawal, Q Zhao
May 21, 1998·Antisense & Nucleic Acid Drug Development·S Agrawal, Q Zhao
Jun 4, 1999·Antisense & Nucleic Acid Drug Development·P C GokhaleU Kasid
Sep 8, 2009·Oligonucleotides·Pablo Reyes-Gutiérrez, Luis M Alvarez-Salas
Nov 10, 2001·Annual Review of Biomedical Engineering·C M Roth, M L Yarmush
Jan 5, 2002·Journal of Drug Targeting·M Kabbaj, N C Phillips
Apr 26, 2006·Expert Opinion on Emerging Drugs·Elizabeth Rose RayburnRuiwen Zhang
Jul 31, 2004·Trends in Biotechnology·Zain Paroo, David R Corey
Sep 6, 2006·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·N ToubP Couvreur
Apr 1, 2015·Nucleic Acid Therapeutics·Manuel SchmidtBurghardt Wittig
Jun 16, 2012·RNA Biology·Chiara Pastori, Claes Wahlestedt
Aug 6, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mattie Bremmer-BoutJudith C T van Deutekom
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Mar 16, 2002·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·S ChamorroN Levens

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