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Issue 1091 coverSignal Transduction Pathways, Part B: Stress Signaling and Transcriptional Control Volume 1091 published December 2006
Ann. N.Y. Acad. Sci. 1091: 110–122 (2006). doi: 10.1196/annals.1378.060
Copyright © 2006 by the New York Academy of Sciences
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Part I. Oxidative Stress

Alterations in Salivary Antioxidants, Nitric Oxide, and Transforming Growth Factor-beta1 in Relation to Disease Activity in Crohn's Disease Patients

ALI REZAIEa, FAKHTEH GHORBANIa, AZADEH ESHGHTORKa, MOHAMMAD J. ZAMANIa, GHOLAMREZA DEHGHANa, BARDIA TAGHAVIa, SHEKOUFEH NIKFARa, AZADEH MOHAMMADIRADa, NASSER E. DARYANIb AND MOHAMMAD ABDOLLAHIa

a Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran 14155-6451, Iran b Department of Gastrointestinal Diseases, Faculty of Medicine, Tehran University of Medical Sciences, Tehran 14155-6451, Iran

Key Words: salivary antioxidants • nitric oxide • transforming growth factor • disease activity index • Crohn's disease • inflammatory bowel disease • saliva • ulcerative colitis

Address for correspondence: Prof. Mohammad Abdollahi, Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14155-6451, Iran. Voice/fax: +98-21-66959104.  e-mail: mohammad.abdollahi{at}utoronto.ca

It has been postulated that oxidative stress, nitric oxide (NO), and transforming growth factor beta1 (TGF- beta1) 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- beta1 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 µg/mL), and uric acid (3.1 ± 1.4 vs. 4.1 ± 2.0 mg/dL) were found. TGF-beta1 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 µmol/L) along with a fivefold increase in LPO concentration (0.146 ± 0.064 vs. 0.027 ± 0.019 µmol/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 (r2 = 0.625, r2 = 0.8, F-test's P < 0.00005). Saliva of CD patients exhibits an abnormal feature with respect to oxidative stress, NO, and TGF-beta1. 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.






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