title: Novel effects of ectoine, a bacteria-derived natural tetrahydropyrimidine, in experimental colitis.
abstract: Evidence suggests an important role of intestinal barrier dysfunction in the etiology of inflammatory bowel disease (IBD). Therefore stabilizing mucosal barrier function constitutes a new therapeutic approach in its management. Ectoine is a compatible solute produced by aerobic chemoheterotrophic and halophilic/halotolerant bacteria, where it acts as osmoprotectant and effective biomembrane stabilizer, protecting the producing cells from extreme environmental stress. Since this natural compound was also shown to prevent inflammatory responses associated with IBD, its potential usefulness was studied in a model of colitis. Groups of rats were treated orally with different doses of ectoine (30-300 mg/kg) or sulfasalazine (reference drug) daily for 11 days. On day 8 colitis was induced by intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid, when overt signs of lesions develop within the next 3 days. On day 12, blood was withdrawn from the retro-orbital plexus of the rats and the animals were sacrificed. The colon was excised and examined macroscopically and microscopically. Relevant parameters of oxidative stress and inflammation were measured in serum and colon homogenates. Induction of colitis led to marked weight loss, significant histopathological changes of the colon, and variable changes in levels of myeloperoxidase, reduced glutathione, malondialdehyde, and all inflammatory markers tested. Treatment with ectoine ameliorated the inflammatory changes in TNBS-induced colitis. This effect was associated with reduction in the levels of TNF-α, IL-1β, ICAM-1, PGE2 and LTB4. The findings suggest that intestinal barrier stabilizers from natural sources could offer new therapeutic measures for the management of IBD.
authors: Heliopolis University, Cairo, Egypt. heba.abdelaziz@gmail.com
authors: Heba
authors: H
authors: Abdel-Aziz
authors: Walaa
authors: W
authors: Wadie
authors: Dalaal M
authors: DM
authors: Abdallah
authors: Georg
authors: G
authors: Lentzen
authors: Mohamed T
authors: MT
authors: Khayyal
mesh_terms: D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012460:Sulfasalazine / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000599:Amino Acids, Diamino; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007975:Leukotriene B4; D012460:Sulfasalazine; D008315:Malondialdehyde; C045628:ectoine; D014302:Trinitrobenzenesulfonic Acid; D005978:Glutathione; D015232:Dinoprostone