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Updated: Aug 4, 2026
Rat Mesentery Angiogenesis Assay
Published on: June 18, 2011
Metabonomic assessment of vasculitis in rats
D G Robertson1, M D Reily, M Albassam
1Department of Drug Safety Evaluation, Pfizer Global Research and Development, Ann Arbor, MI 48106-1047, USA. donald.robertson@pfizer.com
Abstract:
The vasculitides are a heterogeneous group of lesions characterized by inflammation and necrosis of the vascular wall and have proven to be a disconcerting dilemma in the development of several classes of therapeutics. Metabonomics is an emerging technology having great potential for rapid noninvasive assessment of toxicity in vivo and providing identification of peripheral surrogate markers of toxicity. Metabonomic evaluation of CI-1018, a selective type 4 phosphodiesterase inhibitor associated with vasculitis in rats, was undertaken. Two experiments were performed in which CI-1018 was administered for up to 4 d to groups of male Wistar rats at doses up to 3000 mg/kg. Urine was collected from all animals pretest and daily for metabonomic analysis. Eleven of 38 CI-1018-treated animals were found to have vascular injury of varying severity at doses = or > 750 mg/kg. Principal component analysis produced a clear pattern separation among 8 of 11 animals with lesions and 36 of 37 animals without lesions in samples collected on d 3 or 4. These data demonstrate that the metabonomics approach has significant potential for developing a noninvasive method for identifying vasculitis in rats. It remains to be seen if urinary analyte patterns identified in this study are reproducible and whether a biomarker pattern for vasculitis can be established.
Insights
Metabonomics, a novel technique, can noninvasively detect vasculitis (vascular inflammation) in rats. This approach shows promise for identifying toxicity and establishing biomarkers for vascular injury.
Area of Science:
- Biochemistry
- Toxicology
- Pharmacology
Background:
- Vasculitides are complex vascular diseases posing therapeutic challenges.
- Metabonomics offers rapid, noninvasive assessment of in vivo toxicity and biomarker identification.
Purpose of the Study:
- To evaluate the utility of metabonomics for detecting vasculitis induced by CI-1018 in rats.
- To identify potential urinary surrogate markers for vascular injury.
Main Methods:
- CI-1018, a phosphodiesterase 4 inhibitor, was administered to Wistar rats.
- Urine samples were collected daily for metabonomic analysis.
- Principal component analysis was used to analyze metabolic profiles.
Main Results:
- Vascular injury was observed in 11 of 38 CI-1018-treated rats at doses >= 750 mg/kg.
- Metabonomic analysis distinguished between rats with and without vascular lesions.
- Clear pattern separation was achieved on days 3 or 4 post-administration.
Conclusions:
- Metabonomics shows significant potential as a noninvasive method for identifying vasculitis in rats.
- Further studies are needed to confirm reproducibility and establish a definitive biomarker pattern for vasculitis.
