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Inflamm Bowel Dis. 2014 Aug;20(8):1435-47. doi: 10.1097/MIB.0000000000000118.

In vivo imaging of reactive oxygen and nitrogen species in murine colitis.

Author information

1
*Department of Biosciences, Cell Biology, Åbo Akademi University, Biocity, Turku, Finland; †Department of Medical Microbiology and Immunology, and ‡Turku PET Center, Medicity Research Laboratory, University of Turku, Turku, Finland; §Medical Inflammation Research, MBB, Karolinska Institutet, Stockholm, Sweden; ‖Medicity Research Laboratory, University of Turku, Turku, Finland; and ¶Turku Center for Disease modeling, Turku, Finland.

Abstract

BACKGROUND:

Traditional techniques analyzing mouse colitis are invasive, laborious, or indirect. Development of in vivo imaging techniques for specific colitis processes would be useful for monitoring disease progression and/or treatment effectiveness. The aim was to evaluate the applicability of the chemiluminescent probe L-012, which detects reactive oxygen and nitrogen species, for in vivo colitis imaging.

METHODS:

Two genetic colitis mouse models were used; K8 knockout (K8(-/-)) mice, which develop early colitis and the nonobese diabetic mice, which develop a transient subclinical colitis. Dextran sulphate sodium was used as a chemical colitis model. Mice were anesthetized, injected intraperitoneally with L-012, imaged, and quantified for chemiluminescent signal in the abdominal region using an IVIS camera system.

RESULTS:

K8(-/-) and nonobese diabetic mice showed increased L-012-mediated chemiluminescence from the abdominal region compared with control mice. L-012 signals correlated with the colitis phenotype assessed by histology and myeloperoxidase staining. Although L-012 chemiluminescence enabled detection of dextran sulphate sodium-induced colitis at an earlier time point compared with traditional methods, large mouse-to-mouse variations were noted. In situ and ex vivo L-012 imaging as well as [18F]FDG-PET imaging of K8(-/-) mice confirmed that the in vivo signals originated from the distal colon. L-012 in vivo imaging showed a wide variation in reactive oxygen and nitrogen species in young mice, irrespective of K8 genotype. In aging mice L-012 signals were consistently higher in K8(-/-) as compared to K8(+/+) mice.

CONCLUSIONS:

In vivo imaging using L-012 is a useful, simple, and cost-effective tool to study the level and longitudinal progression of genetic and possibly chemical murine colitis.

PMID:
24983980
DOI:
10.1097/MIB.0000000000000118
[Indexed for MEDLINE]

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