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The effect of PARS inhibition on ileal histopathology, apoptosis and lipid peroxidation in LPS-induced obstructive jaundice.

Abstract
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.
AuthorsMusa Dirlik, Mehmet Caglikulekci, Ismail Cinel, Leyla Cinel, Lülüfer Tamer, Cengiz Pata, Arzu Kanik, Koray Ocal, Zekai Ogetman, Süha Aydin
JournalPharmacological research (Pharmacol Res) Vol. 48 Issue 2 Pg. 139-49 (Aug 2003) ISSN: 1043-6618 [Print] Netherlands
PMID12798666 (Publication Type: Journal Article)
Chemical References
  • Benzamides
  • Lipopolysaccharides
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Malondialdehyde
  • 3-aminobenzamide
  • Adenosine Triphosphatases
Topics
  • Adenosine Triphosphatases (metabolism)
  • Analysis of Variance
  • Animals
  • Apoptosis (drug effects)
  • Benzamides (pharmacology, therapeutic use)
  • Disease Models, Animal
  • Endotoxemia (etiology, metabolism)
  • Ileum (drug effects, pathology)
  • Immunohistochemistry
  • Jaundice, Obstructive (chemically induced, complications, drug therapy, pathology)
  • Lipid Peroxidation (drug effects)
  • Lipopolysaccharides
  • Male
  • Malondialdehyde (analysis, blood)
  • Oxidative Stress (drug effects)
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Rats
  • Rats, Wistar

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