Effect of a new de-N-acetyl-lysoglycosphingolipid on chemically-induced inflammatory bowel disease: possible mechanism of action.
A new, orally active de-N-acetylated lysoglycosphingolipid (WILD20) was evaluated as antiinflammatory agent using a model of chemically-induced inflammatory bowel disease (IBD) in the rat to mimic human ulcerative colitis and Chron's disease. IBD was induced by hapten trinitrobenzenesulphonic acid (TNB). WILD20, orally administered as preventive or curative, was demonstrated to be efficacious at daily dosages of 0.1-1 mg/kg for 4-5 days. Damage scores, body weight, spleen weight, colonic tissular levels of LTB4, myeloperoxidase (MPO) and malondialdehyde (MDA) are influenced and brought into parameters of normality. Histological observation demonstrated quicker healing, better repair, reduced inflammation, and poor eosinophil degranulation. The mechanisms underlying WILD20 antiinflammatory effects were investigated: whereas WILD20 fails to show a direct effect on PKC, it reduces PKC translocation to the membrane; cellular PLA2 was consequently greatly reduced through this mechanism and thought to be responsible for WILD20 efficacy towards chemically-induced IBD.
Tubaro
E
E
Wellcome Italia Research Laboratories, Pomezia, Rome.
Santiangeli
C
C
Cavallo
G
G
Belogi
L
L
Guida
G
G
Croce
C
C
Modesti
A
A
D000818:Animals; D016718:Arachidonic Acid / Q000097:blood / Q000378:metabolism; D002240:Carbohydrate Sequence; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D005732:Gangliosides / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008969:Molecular Sequence Data; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects; D013582:Synovial Fluid / Q000187:drug effects / Q000201:enzymology; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
D005732:Gangliosides; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; C084337:WILD 20; D007975:Leukotriene B4; D016718:Arachidonic Acid; D008315:Malondialdehyde; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D010741:Phospholipases A; D054467:Phospholipases A2