Acute drug-induced vascular injury in beagle dogs: pathology and correlating genomic expression

Toxicologic Pathology
Bradley E EnersonEugenia Floyd

Abstract

Acute vascular injury that leads to vascular inflammation is a common finding in the preclinical toxicity testing of drugs in rats and dogs. However, the relevance of this finding for risk to humans is unclear. Concern about the safety of these drugs is heightened by the current lack of noninvasive clinical methods to predict the onset of vascular damage in animals or humans. Determining the relevance of this poorly understood preclinical outcome for humans requires a better understanding of the molecular mechanisms of injury in addition to the development of sensitive and specific leading biomarkers for the clinical diagnosis of acute vascular damage. Most molecular research on this toxicity has been performed in rats, but recent development of canine gene expression microarrays makes transcriptomic studies now possible in the dog. In this study, we investigated the molecular mechanisms of drug-induced vascular injury in dogs using gene arrays. After treating Beagles with toxic doses of CI-947, an adenosine receptor agonist, we profiled gene expression in the coronary arteries and correlated those changes with histopathology at 16 and 24 hours after dosing. The results demonstrated that pathobiological processes such as stimul...Continue Reading

References

Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Jun 1, 1995·Microscopy Research and Technique·M H Stromer
Oct 6, 1999·Circulation·D W SteppW M Chilian
Dec 1, 2001·Pharmacology & Therapeutics·R Tabrizchi, S Bedi
Jan 26, 2002·Briefings in Bioinformatics·G Sherlock
Jun 18, 2002·Hospital Medicine·J M Fellick, A P J Thomson
Jul 13, 2002·Lancet·A E Grulich, J M Kaldor
Aug 31, 2002·Endothelium : Journal of Endothelial Cell Research·Shailesh Y DesaiDamir Janigro
Feb 25, 2003·Toxicologic Pathology·Frances A S ClemoMudher A Albassam
May 7, 2003·Progress in Biophysics and Molecular Biology·Nitzan ResnickEfrat Wofovitz
Jun 6, 2003·Progress in Neurobiology·Jana Sawynok, Xue Jun Liu
Dec 31, 2003·Trends in Immunology·György Haskó, Bruce N Cronstein
Aug 24, 2004·Current Vascular Pharmacology·Keiji YamamotoKazuyuki Shimada
Nov 13, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Huda E TawfikS Jamal Mustafa
Feb 8, 2005·Toxicology and Applied Pharmacology·William KernsUNKNOWN Expert Working Group on Drug-Induced Vascular Injury

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Citations

Jul 1, 2006·Bioinformatics·Herbert PangHongyu Zhao
Apr 19, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Christopher M ShethJames L Weaver
Jun 21, 2011·Comparative and Functional Genomics·Sook S HaJianhua Xuan
Jun 2, 2015·Expert Opinion on Drug Metabolism & Toxicology·George A Truskey, Cristina E Fernandez
Jan 16, 2007·Vascular Pharmacology·Belay Tesfamariam, Albert F DeFelice
Jun 16, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Nicolas DaguèsStephan Chevalier
Sep 15, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Mark M GosinkMichael P Lawton
Apr 16, 2019·Journal of Medicinal Chemistry·Joey L MethotJason D Katz
Dec 19, 2020·ACS Medicinal Chemistry Letters·Joey L MethotJason D Katz

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Methods Mentioned

BETA
light microscopy
in vitro transcription
chip

Software Mentioned

BLASTx
dChip

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