Fecal N-Methylhistamine Concentrations in Norwegian Lundehunds with Gastrointestinal Disease
It has previously been suggested that mast cells play a role in the pathogenesis of inflammatory bowel disease (IBD) and other gastroenteropathies. Mast cells release inflammatory mediators, including histamine. Histamine is metabolized by two major enzymatic pathways, one of which yields N-methylhistamine (NMH). The purpose of this study was to compare fecal NMH concentrations in a group of Norwegian Lundehunds with chronic gastroenteropathy to those in a group of healthy control dogs. Norwegian Lundehunds are known to have a high prevalence of chronic gastroenteropathies, and were thus chosen as an initial study group.
Three fecal samples each were collected from 10 healthy control dogs and 21 Norwegian Lundehunds with chronic gastrointestinal (GI) disease. Histopathology was not available, but all Lundehunds had clinical signs of GI disease and/or showed abnormal results of GI function tests, including decreased serum cobalamin, folate, total protein, and/or albumin concentrations and/or increased fecal α1-proteinase inhibitor concentrations. Samples for NMH analysis were extracted and analyzed as previously described (Tredget, EE. Journal of Chromatography B, 1997), using stable isotope dilution gas chromatography/mass spectrometry. Data were analyzed for normality and the medians of the maximum NMH concentration for the 3-day collection period and of the 3-day average NMH concentration were compared between the two groups (Mann-Whitney U test). Statistical significance was set at p<0.05. Maximum and 3-day average NMH concentrations in the group of Lundehunds were also evaluated for correlation with fecal α1-proteinase inhibitor concentrations and serum cobalamin, folate, total protein, albumin, and C-reactive protein concentrations.
The triplicate samples from control dogs had maximum NMH concentrations between 13.8 and 321.7 ng/g feces (median: 57.3 ng/g), whereas those for the Lundehund samples ranged from 85.9 to 14,300 ng/g (median: 374.4 ng/g; p=0.0004). Median 3-day average NMH concentrations in the Lundehunds were significantly higher (median: 284.7 ng/g; range: 66.9-9,319 ng/g) than in the control dogs (median: 44.5 ng/g; range: 8.9-196.9 ng/g; p=0.0005). Fecal NMH concentrations did not correlate with fecal α1-proteinase inhibitor concentrations or serum cobalamin, folate, total protein, albumin, or C-reactive protein concentrations.
These data show that fecal NMH was significantly increased in a group of Lundehunds with chronic GI disease. A potential shortcoming of this study is the lack of histopathology in the affected Lundehunds. However, all dogs examined had clinical signs and/or abnormal GI function tests. Intestinal mast cell degranulation and histamine release may also play a role in other dogs with gastroenteropathies. Thus, further studies are needed and ongoing in order to assess fecal NMH concentrations in dogs of other breeds with gastroenteropathies.