The effect of PARS inhibition on ileal histopathology, apoptosis and lipid peroxidation in LPS-induced obstructive jaundice.
In our experimental study, we investigated the protective effect of 3-aminobenzamide (3-AB), the poly (ADP-ribose) synthetase (PARS inhibitor), on the ileal histopathology and the apoptosis in lipopolysaccharide (LPS)-induced inflammation in rats with obstructive jaundice (OJ). We randomized 40 rats into five groups. Group 1: sham group; Group 2: OJ group; Group 3: OJ+LPS; Group 4: OJ+3-AB+LPS; Group 5: OJ+LPS+3-AB. At the fifth day; the rats were jaundiced. In Group 3; 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and then after 6h the rats were sacrificed. In Group 4; 10 mg kg(-1) 3-AB was administrated intraperitoneally at the fifth day and repeated daily for 3 days and at the eighth day, 10 mg kg(-1) LPS was injected intraperitoneally. In Group 5, 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and after 6h 10 mg kg(-1) 3-AB was administrated intraperitoneally and repeated daily for 3 days. At the eighth day, rats were sacrificed. Blood samples were taken for detection of serum MDA levels. Ileum samples were taken after relaparotomy for histopathological examination to evaluate the endotoxin-related intestinal injury and Caspase-3 apoptosis and for detection of tissue MDA and ATPase activities. There was marked destruction of villous and crypt epithelial cells and extensive apoptosis in Groups 3 and 5 in histopathological examination. In Group 4, the scores of intestinal mucosal damage and apoptotic cells were reduced significantly (P<0.05). On the other hand, the scores of intestinal mucosal damage and apoptotic cells were not improved in Group 5. After the administration of 3-AB (Group 4), serum and ileal MDA levels decreased, ileal ATPase increased as compared to Groups 1 and 2. Our study showed that 3-AB prevented the mucosal damage and apoptotic loss of intestinal epithelial cells significantly if it was administrated before LPS. However, 3-AB failed to prevent the mucosal damage and apoptotic loss of intestinal epithelial cells significantly if there was established endotoxemia in OJ.
Dirlik
Musa
M
Department of General Surgery, Faculty of Medicine, Mersin University Medical School, Zeytinlibahçe Caddesi, Eski Otogar Yani 33079, Mersin, Turkey. musa_dirlik@yahoo.com
Caglikulekci
Mehmet
M
Cinel
Ismail
I
Cinel
Leyla
L
Tamer
Lülüfer
L
Pata
Cengiz
C
Kanik
Arzu
A
Ocal
Koray
K
Ogetman
Zekai
Z
Aydin
Süha
S
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000209:etiology / Q000378:metabolism; D007082:Ileum / Q000187:drug effects* / Q000473:pathology; D007150:Immunohistochemistry; D041781:Jaundice, Obstructive / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D017208:Rats, Wistar
D001549:Benzamides; D008070:Lipopolysaccharides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D008315:Malondialdehyde; C025160:3-aminobenzamide; D000251:Adenosine Triphosphatases