title: Quantitative evaluation of drug-induced microvascular constriction in mice kidney using a novel tool for 3D geometrical analysis of ex vivo organ vasculature.
abstract: The analysis of organ vasculature, and more specifically organ microvasculature, carries special importance for toxicological sciences, and especially for evaluation of drug-induced vascular toxicity. This field presents a special challenge in nonclinical drug safety assessments since there are currently no reliable microvascular toxicity biomarkers. Therefore, we aimed to systematically investigate the use of microvascular 3D geometrical analysis of corrosion casts for evaluation of drug-induced vascular toxicity, utilizing a novel image investigation tool that allows full 3D-quantified geometrical analysis of the entire vascular tree structure. Vascular casts of kidneys from control and low- and high-dose ephedrine/caffeine-treated mice were scanned by a micro CT, and images were processed and analyzed using the Vasculomics™ platform. All evaluations were performed on the kidney cortex. Treatment resulted in a significant and dose-related reduction in overall microvessel density throughout the kidney cortex. This effect was most pronounced for vessels with diameters between 25 µm and 35 µm, and affected mostly vessels located in the superficial part of the kidney cortex. The use of 3D analysis tools in drug-induced vascular toxicity studies allows for very high resolution and characterization of drug effects on the microvasculature and can be used as a valuable tool in drug safety assessments.
authors.affiliation: Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Ramot
authors.affiliation: Bio-Tree Systems Inc., Framingham, Massachusetts, USA raulb@bio-tree.com.
authors.forename: Raul
authors.initials: R
authors.lastname: Brauner
authors.affiliation: Bio-Tree Systems Inc., Framingham, Massachusetts, USA.
authors.forename: Kongbin
authors.initials: K
authors.lastname: Kang
authors.affiliation: Bio-Tree Systems Inc., Framingham, Massachusetts, USA Thoracic, Head and Neck Oncology Department, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: John V
authors.initials: JV
authors.lastname: Heymach
authors.affiliation: Bio-Tree Systems Inc., Framingham, Massachusetts, USA Brown University, Providence, Rhode Island, USA.
authors.forename: Stacia
authors.initials: S
authors.lastname: Furtado
authors.affiliation: Consultant in Toxicologic Pathology, Sackler School of Medicine, Tel Aviv University, Timrat, 36576, Israel anyska@bezeqint.net.
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
mesh_terms: D000818:Animals; D003250:Constriction; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008855:Microscopy, Electron, Scanning; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D057772:Vascular System Injuries / Q000139:chemically induced / Q000473:pathology*; D055114:X-Ray Microtomography
keywords: drug-induced; vascular corrosion casts.; vascular toxicity