Effects of lexipafant (BB-882), a platelet activating factor receptor antagonist, on liver damage due to bile duct ligation in rats.
OBJECTIVE
Extrahepatic cholestasis is one of the main factors causing liver fibrosis. In this study, we aimed to evaluate the effects of lexipafant (BB-882), a platelet activating factor receptor antagonist, on liver damage in rats with bile duct ligation.


METHODS
A total of 30 male Sprague-Dawley rats weighing 160-190 g were used in this study. Group 1 (Sham-control, n = 10) rats were undergone laparotomy alone and bile duct was just dissected from the surrounding tissue. Group 2 rats (BDL/Untreated, n = 10) were subjected to bile duct ligation and no drug was applied. Group 3 rats (BDL/BB-882, n = 10) received a daily dose of BB-882 intraperitoneally for 14 days after BDL. At the end of the two-week period, biochemical and histological evaluation was processed.


RESULTS
The mean serum bilirubin and liver enzymes level significantly decreased, and Superoxide dismutase, catalase and glutathione peroxidase values were significantly increased in BDL/BB-882 group when compared to BDL/Untreated group. The histopathological score was significantly less in the BDL/BB-882 group compared to the BDL/Untreated rats. In the BDL/BB-882 group was observed less fibrosis and neutrophil infiltration


CONCLUSIONS
These results suggest that BB-882 (lexipafant) may reduce the severity of the inflammatory response to liver injury produced by bile duct ligation in rats.
Oztürk
Hulya
H
Diyarbakir Children Hospital, Department of Pediatric Surgery, Diyarbakir, Turkey.
Oztürk
Hayrettin
H
Dokucu
Ali Ihsan
AI
Otcu
Selcuk
S
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002374:Catalase / Q000097:blood; D001651:Cholestasis, Extrahepatic / Q000150:complications* / Q000201:enzymology / Q000601:surgery*; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000097:blood; D007093:Imidazoles / Q000494:pharmacology*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008026:Ligation / Q000009:adverse effects; D008103:Liver Cirrhosis / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D013482:Superoxide Dismutase / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
C094498:BB 882; D007093:Imidazoles; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D007930:Leucine; C103289:lexipafant; D001663:Bilirubin