Alterations in Salivary Antioxidants, Nitric Oxide, and Transforming Growth Factor‐β₁ in Relation to Disease Activity in Crohn's Disease Patients

Abstract

It has been postulated that oxidative stress, nitric oxide (NO), and transforming growth factor beta(1) (TGF- beta(1)) have major roles in the pathophysiology of Crohn's disease (CD). The aim of this study was to determine the salivary levels of total antioxidant capacity (TAC), specific antioxidants (i.e., uric acid, albumin, transferrin, and thiol molecules), lipid peroxidation (LPO), NO, and TGF- beta(1) in CD patients and control subjects and to also investigate their correlation with activity of the disease. Twenty-eight patients with confirmed diagnosis of CD were enrolled and whole saliva samples were obtained. Smokers, diabetics, those who suffered from periodontitis, and those who were consuming antioxidant supplements were excluded from the study. The Crohn's Disease Activity Index (CDAI) was used to determine the severity of the disease. Twenty healthy subjects were also recruited. In CD patients significant reductions in salivary levels of TAC (0.248 +/- 0.145 vs. 0.342 +/- 0.110 mmol/L), albumin (1.79 +/- 0.42 vs. 2.3 +/- 0.2 microg/mL), and uric acid (3.1 +/- 1.4 vs. 4.1 +/- 2.0 mg/dL) were found. TGF-beta(1) was significantly increased in CD patients compared to healthy subjects (3.02 +/- 1.54 vs. 2.36 +/- 0.52 ng/mL). A fourfold increase in NO levels (198.8 +/- 39.9 vs. 50.2 +/- 21.3 micromol/L) along with a fivefold increase in LPO concentration (0.146 +/- 0.064 vs. 0.027 +/- 0.019 micromol/L) was documented in CD patients in comparison to the control group. CDAI significantly correlated with the TAC, LPO, and the interaction between TAC and LPO (r(2) = 0.625, r(2) = 0.8, F-test's P < 0.00005). Saliva of CD patients exhibits an abnormal feature with respect to oxidative stress, NO, and TGF-beta(1). TAC and LPO modify the effect of each other in determination of CD severity, which underlines the importance of oxidative stress in the pathogenesis of CD.

Molecular evidences on the benefit of N-acetylcysteine in experimental colitis

“…Both neutrophils and macrophages recruited to the site of inflammation express iNOS and produce a large amount of NO [14,15]. The overproduction of NO seems to play a role in the pathogenesis of IBD [16][17][18]. Among different inflammatory mediators that have been implicated in IBD, tumor necrosis factor-alpha (TNF-α) is prominent.…”

Periodontal and inflammatory bowel diseases: Is there evidence for complex pathogenic interactions?

“…Szczeklik et al [49] have found higher salivary levels of IL-1β, IL-6, and TNF-α in patients with active CD than in patients with inactive disease and in controls. Interestingly, CD patients also presented significant reductions in total antioxidant capacity, and increased TGF-β(1), nitric oxide, and lipid peroxidation [50] ; UC patients presented higher TGF-β(1) and nitric oxide levels in comparison to the control group [52] . Decreased lysozyme and increased IgA and LL37 in saliva have also been reported in CD and UC patients [46] .…”

“…Increased levels of pro-inflammatory cytokines have been found in IBD patients, especially those with active disease [49,50] . Aleksandra Nielsen et al [51] have reported increased salivary levels of IL-6 in patients with CD and not in patients with UC, but only seven patients were analysed in the UC group.…”

Antioxidant status of the celiac mucosa: implications for disease pathogenesis

“…Various theories regarding the initiation of the inflammatory response in the intestinal mucosa have been proposed, but none of them is universally accepted (Hendrickson et al, 2002). Many studies have reported the increased concentrations of oxidized biomolecules and the decreased concentrations of various antioxidants in patients affected by IBD, not only in the intestinal mucosa, but also in other parts of the gastrointestinal tract, as well as in the blood and respiratory system (Rezaie et al 2006). It is known that oxidizing agents can induce clinical and histological alterations characteristic of IBD (Bilotta & Waye, 1989;Meyer et al 1981).…”