Positive Correlation Between Disease Activity Index and Matrix Metalloproteinases Activity in a Rat Model of Colitis

Oliveira, Luiz Gustavo de; Cunha, André Luiz da; Duarte, Amaury Caiafa; Castañon, Maria Christina Marques Nogueira; Chebli, Júlio Maria Fonseca; Aguiar, Jair Adriano Kopke de

doi:10.1590/s0004-28032014000200007

Cited by 17 publications

(16 citation statements)

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“…We found a positive correlation between active MMP-9 activities in the ileal mucosa and the CIBDAI score before treatment in dogs with CE, which is similar to the relationship between mucosal MMP-9 and the disease activity index in a rat model of colitis [ 31 ], and between fecal MMP-9 and clinical activities of ulcerative colitis in humans [ 32 ]. However, due to the low number of active MMP-9-positive samples (n = 3) in the ileal samples of dogs with CE in our study, the results should not be over-interpreted.…”

Section: Discussionsupporting

confidence: 56%

Identification of matrix metalloproteinase-2 and -9 activities within the intestinal mucosa of dogs with chronic enteropathies

et al. 2018

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BackgroundMatrix metalloproteinases (MMPs) 2 and 9 are zinc- and calcium-dependent endopeptidases involved in the breakdown and reconstitution of extracellular matrix under both physiological and pathological conditions. Mucosal MMP-2 and -9 activities have been reported to be upregulated in the intestine of humans with inflammatory bowel disease (IBD), and in animal models of IBD. However, their involvement in the pathogenesis of canine chronic enteropathies (CE) is unknown. This study investigated mucosal pro- and active MMP-2 and -9 activities in dogs with CE and healthy dogs using gelatin zymography, and also to determine the association of their activities in dogs with CE with the canine IBD activity index (CIBDAI), histopathologic findings, the clinical outcome, and hypoalbuminemia. Intestinal mucosal samples from duodenum, ileum, colon, and cecum were collected from 40 dogs with CE and 18 healthy Beagle dogs.ResultsIn dogs with CE, the number of samples positive for mucosal pro- and active MMP-2 was significantly higher in the duodenum (P < 0.0001 and P = 0.011, respectively), ileum (P = 0.002 and P = 0.018, respectively), and colon (P < 0.0001 and P = 0.002, respectively), compared with healthy controls. Mucosal pro-MMP-9-positive samples in the duodenum and colon were significantly more frequent in dogs with CE than in healthy dogs (P = 0.0004 and P = 0.001, respectively). Despite the presence of mucosal samples positive for active MMP-9 in the intestinal segments of dogs with CE, the difference compared to healthy controls did not reach statistical significance. None of the intestinal mucosal samples in healthy dogs showed gelatinolytic activity corresponding to the control bands of active MMP-2 and -9. Mucosal active MMP-9 activities displayed a significant positive association with the severity of neutrophil infiltration in the duodenum (P = 00.040), eosinophils in the cecum (P = 00.037), and the CIBDAI score for ileum samples (P = 0.023). There was no significant association of pro- and active MMP-2 and -9 levels with the clinical outcome or hypoalbuminemia.ConclusionsThis study is the first to demonstrate upregulation of mucosal pro- and active MMP-2 and pro-MMP-9 in the intestine of dogs with CE compared to healthy dogs. The results provide supporting evidence for the possible involvement of MMP-2 and -9 in the pathogenesis of canine CE.

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Section: Discussionsupporting

confidence: 56%

Identification of matrix metalloproteinase-2 and -9 activities within the intestinal mucosa of dogs with chronic enteropathies

et al. 2018

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“…In a DSS-induced rat model of colitis, a positive correlation of disease activity index with the degree of histopathological damage and increased levels of MMP-9 and myeloperoxidase/MPO was shown (Oliveira et al, 2014). In previous studies it was shown that homocysteine levels were increased in plasma and mucosal tissue from CD patients (Kallel et al, 2011).…”

Section: Involvement Of Mmps and Timps In Animal Models Of Colitismentioning

confidence: 90%

The molecular biology of matrix metalloproteinases and tissue inhibitors of metalloproteinases in inflammatory bowel diseases

Bruyn¹,

Vandooren

Ugarte-Berzal

et al. 2016

Critical Reviews in Biochemistry and Molecular Biology

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Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be predominant proteases and protease inhibitors involved in the pathogenesis of inflammatory bowel diseases (IBD) through their ability to remodel the extracellular matrix (ECM) in response to inflammatory stimuli and by their immunomodulating effects. An imbalance between MMPs and TIMPs has been linked with acute and chronic inflammation and aberrant tissue remodeling, as seen in IBD. Moreover, recurrent phases of tissue destruction and subsequent tissue repair can cause serious complications in IBD patients such as fistulas and fibrosis. The aims of this review are (i) to summarize current literature on genetic association, mRNA, and protein expression studies with regard to MMPs and TIMPs in IBD patients and various animal models, including those with transgenic and knockout mice; (ii) to compare biochemical and molecular biological data in humans with those obtained in animal model studies and (iii) to critically evaluate and translate how this knowledge may be used in practical terms to understand better the pathophysiology and mechanisms operating in IBD and to apply this for improvement of clinical outcomes at diagnostic, prognostic and therapeutic levels.

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“…Rectal bleeding may be due to multifocal areas of erosions and ulcerations. Also, diarrhea could be due to hyperosmolarity in the colonic lumen and/or increased intestinal cell permeability caused by DSS . Hesperidin treatment ameliorated body weight loss, colonic weight/length ratio, and DAI, which may be attributed to its anti‐inflammatory effects and its ability to restore metabolism and cellular biosynthesis .…”

Section: Discussionmentioning

confidence: 99%

Hesperidin modulates dextran sulfate sodium‐induced ulcerative colitis in rats: Targeting sphingosine kinase‐1‐ sphingosine 1 phosphate signaling pathway, mitochondrial biogenesis, inflammation, and apoptosis

Shafik

Gaber

Mohamed

et al. 2019

J Biochem & Molecular Tox

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Ulcerative colitis (UC) is a chronic gastrointestinal disorder interfering with life quality. A total of 60 male Wistar rats were divided into four equal groups: Control (group I), hesperidin only (group II), UC untreated (group III), and UC treated with hesperidin (group IV). Hesperidin had modulatory effects on UC pathogenesis, which might be through alleviating colonic sphingosine phosphate phosphatase 2 messenger RNA expression and sphingosine kinase-1 levels, thus suppressing the subsequent downstream inflammatory and apoptotic cascades represented by decreased macrophage inflammatory protein-1α and enhancement of B-cell lymphoma 2 immunohistochemistry expression. Also, it improved mitochondrial biogenesis by increasing the peroxisome proliferator-activated receptor-gammacoactivator 1-α level. It successfully restored redox potential as evidenced by marked alleviations of the nitric oxide and peroxynitrite levels, increasing total antioxidant capacity, and activating the superoxide dismutase enzyme. Also, hesperidin alleviated the UC disease activity index and improved the histopathological picture. These findings may offer a new therapeutic strategy for UC treatment. K E Y W O R D S hesperidin, macrophage inflammatory protein-1 alpha, peroxisome proliferator-activated receptor-gamma-coactivator 1-α, sphingosine kinase, ulcerative colitis

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Positive Correlation Between Disease Activity Index and Matrix Metalloproteinases Activity in a Rat Model of Colitis

Cited by 17 publications

References 29 publications

Identification of matrix metalloproteinase-2 and -9 activities within the intestinal mucosa of dogs with chronic enteropathies

Identification of matrix metalloproteinase-2 and -9 activities within the intestinal mucosa of dogs with chronic enteropathies

The molecular biology of matrix metalloproteinases and tissue inhibitors of metalloproteinases in inflammatory bowel diseases

Hesperidin modulates dextran sulfate sodium‐induced ulcerative colitis in rats: Targeting sphingosine kinase‐1‐ sphingosine 1 phosphate signaling pathway, mitochondrial biogenesis, inflammation, and apoptosis

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