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

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.

• Authors: M Nadeem Asghar, Rohini Emani, Catharina Alam, Terhi O Helenius, Tove J Grönroos, Outi Sareila, Mueez U Din, Rikard Holmdahl, Arno Hänninen, Diana M Toivola
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 20 Issue 8 Pg. 1435-47 (Aug 2014) ISSN: 1536-4844 [Electronic] England
• PMID: 24983980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Keratin-8
• Krt8 protein, mouse
• Reactive Nitrogen Species
• Reactive Oxygen Species
• Dextran Sulfate

Topics

• Animals
• Colitis (chemically induced, complications, metabolism, pathology)
• Dextran Sulfate (toxicity)
• Diagnostic Imaging
• Disease Models, Animal
• Female
• Image Processing, Computer-Assisted
• Inflammation (diagnosis, metabolism)
• Keratin-8 (genetics)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred NOD
• Mice, Knockout
• Positron-Emission Tomography
• Reactive Nitrogen Species (metabolism)
• Reactive Oxygen Species (metabolism)