PMID- 18465235
OWN - NLM
STAT- MEDLINE
DCOM- 20090203
LR  - 20211020
IS  - 0163-2116 (Print)
IS  - 0163-2116 (Linking)
VI  - 53
IP  - 12
DP  - 2008 Dec
TI  - Efficacy of intracolonic administration of low-molecular-weight heparin CB-01-05, 
      compared to other low-molecular-weight heparins and unfractionated heparin, in 
      experimentally induced colitis in rat.
PG  - 3170-5
LID - 10.1007/s10620-008-0299-6 [doi]
AB  - 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.
FAU - Celasco, Giuseppe
AU  - Celasco G
AD  - Cosmo Research and Development Srl, Via C. Colombo 1, 20020, Lainate, MI, Italy. 
      giuseppe.celasco@cosmopharmaceuticals.com
FAU - Moro, Luigi
AU  - Moro L
FAU - Bozzella, Roberta
AU  - Bozzella R
FAU - Mangano, Katia
AU  - Mangano K
FAU - Quattrocchi, Cinzia
AU  - Quattrocchi C
FAU - Aiello, Caterina
AU  - Aiello C
FAU - Donia, Marco
AU  - Donia M
FAU - Fagone, Paolo
AU  - Fagone P
FAU - Di Marco, Roberto
AU  - Di Marco R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080509
PL  - United States
TA  - Dig Dis Sci
JT  - Digestive diseases and sciences
JID - 7902782
RN  - 0 (Dinitrobenzenes)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 82115-62-6 (Interferon-gamma)
RN  - M316WT19D8 (parnaparin)
SB  - IM
EIN - Dig Dis Sci. 2009 Jan;54(1):193-4
MH  - Administration, Rectal
MH  - Animals
MH  - Colitis/chemically induced/*drug therapy/pathology
MH  - Dinitrobenzenes
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Fibrinolytic Agents/*administration & dosage/pharmacology
MH  - Heparin, Low-Molecular-Weight/*administration & dosage/pharmacology/therapeutic 
      use
MH  - Interferon-gamma/metabolism
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Spleen/metabolism
EDAT- 2008/05/10 09:00
MHDA- 2009/02/04 09:00
CRDT- 2008/05/10 09:00
PHST- 2008/02/13 00:00 [received]
PHST- 2008/04/10 00:00 [accepted]
PHST- 2008/05/10 09:00 [pubmed]
PHST- 2009/02/04 09:00 [medline]
PHST- 2008/05/10 09:00 [entrez]
AID - 10.1007/s10620-008-0299-6 [doi]
PST - ppublish
SO  - Dig Dis Sci. 2008 Dec;53(12):3170-5. doi: 10.1007/s10620-008-0299-6. Epub 2008 
      May 9.