PURPOSE: Parenteral administration of low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH) resulted effective in improving the symptoms of experimental colitis in rat. Today, there is little information about their activity by intracolonic instillation. The scope of this study was to evaluate the ability of CB-01-05 (a LMWH with a mean molecular weight of about 5,700), compared to a series of other LMWHs and to UFH, directly instilled into the distal colon of the rat, to ameliorate dinitrobenzene (DNB)-induced experimental colitis. METHOD: Adult male Wistar rats underwent colitis induction by intracolonic instillation of DNB. Starting 24 h after colitis induction, CB-01-05 (0.005-0.9 mg), other LMWHs (0.3-0.6 mg), and UFH (0.6 mg) were instilled, by rectal route, into the distal colon once a day for three consecutive days. On the day following the last administration, the animals were sacrificed and the distal colon was isolated, weighed, macroscopically examined, and processed for histology. Additional experiments in rat splenocytes, performed in order to elucidate the anti-inflammatory mechanisms of CB-01-05, were performed. RESULTS: Among the tested items, only CB-01-05 at doses ranging from 0.2 to 0.9 mg was significantly effective in reducing colon weight increase and in improving both the mucosal damaged area and the histological score. The other LMWHs resulted far less effective, showing decreasing activity closely related with the decrease of their molecular weight, thus demonstrating their biological nonequivalence. CB-01-05 resulted also more active than UFH. CB-01-05 was shown to interfere with cytokines production by rat splenocytes, mainly inhibiting interferon (IFN)-gamma expression. CONCLUSIONS: CB-01-05 instilled into the colon is well tolerated, has strong anti-inflammatory effect on DNB-induced colitis in rat, and is the most effective agent among other LMWHs and UFH. These results suggest that the anti-inflammatory activity of CB-01-05, together with its topical administration, could represent a new approach in the management of ulcerative colitis.
PURPOSE: Parenteral administration of low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH) resulted effective in improving the symptoms of experimental colitis in rat. Today, there is little information about their activity by intracolonic instillation. The scope of this study was to evaluate the ability of CB-01-05 (a LMWH with a mean molecular weight of about 5,700), compared to a series of other LMWHs and to UFH, directly instilled into the distal colon of the rat, to ameliorate dinitrobenzene (DNB)-induced experimental colitis. METHOD: Adult male Wistar rats underwent colitis induction by intracolonic instillation of DNB. Starting 24 h after colitis induction, CB-01-05 (0.005-0.9 mg), other LMWHs (0.3-0.6 mg), and UFH (0.6 mg) were instilled, by rectal route, into the distal colon once a day for three consecutive days. On the day following the last administration, the animals were sacrificed and the distal colon was isolated, weighed, macroscopically examined, and processed for histology. Additional experiments in rat splenocytes, performed in order to elucidate the anti-inflammatory mechanisms of CB-01-05, were performed. RESULTS: Among the tested items, only CB-01-05 at doses ranging from 0.2 to 0.9 mg was significantly effective in reducing colon weight increase and in improving both the mucosal damaged area and the histological score. The other LMWHs resulted far less effective, showing decreasing activity closely related with the decrease of their molecular weight, thus demonstrating their biological nonequivalence. CB-01-05 resulted also more active than UFH. CB-01-05 was shown to interfere with cytokines production by rat splenocytes, mainly inhibiting interferon (IFN)-gamma expression. CONCLUSIONS:CB-01-05 instilled into the colon is well tolerated, has strong anti-inflammatory effect on DNB-induced colitis in rat, and is the most effective agent among other LMWHs and UFH. These results suggest that the anti-inflammatory activity of CB-01-05, together with its topical administration, could represent a new approach in the management of ulcerative colitis.
Authors: I Dotan; A Hallak; N Arber; M Santo; A Alexandrowitz; Y Knaani; R Hershkoviz; E Brazowski; Z Halpern Journal: Dig Dis Sci Date: 2001-10 Impact factor: 3.199
Authors: L Cahalon; O Lider; H Schor; A Avron; D Gilat; R Hershkoviz; R Margalit; A Eshel; O Shoseyev; I R Cohen Journal: Int Immunol Date: 1997-10 Impact factor: 4.823
Authors: P Zezos; G Papaioannou; N Nikolaidis; K Patsiaoura; A Papageorgiou; T Vassiliadis; O Giouleme; N Evgenidis Journal: Aliment Pharmacol Ther Date: 2006-05-15 Impact factor: 8.171
Authors: M A de Bièvre; A A Vrij; E J Schoon; G Dijkstra; A E de Jong; A H Oberndorff-Klein Woolthuis; H C Hemker; R W Stockbrügger Journal: Inflamm Bowel Dis Date: 2007-06 Impact factor: 5.325
Authors: L A Dieleman; M J Palmen; H Akol; E Bloemena; A S Peña; S G Meuwissen; E P Van Rees Journal: Clin Exp Immunol Date: 1998-12 Impact factor: 4.330
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Authors: Katia Mangano; Franca Vergalito; Santa Mammana; Andrea Mariano; Rocco De Pasquale; Antonia Meloscia; Silvia Bartollino; Germano Guerra; Ferdinando Nicoletti; Roberto Di Marco Journal: Exp Ther Med Date: 2017-07-19 Impact factor: 2.447