THE ROLE OF POLY(ADP-RIBOSE) SYNTHETASE INHIBITION IN PREVENTING ENDOTOXEMIA-INDUCED INTESTINAL EPITHELIAL APOPTOSIS

• Published in: Pharmacological research 2002-08, Vol.46 (2), p.119-127
• Main Authors: CINEL, ISMAIL, BUYUKAFSAR, KANSU, CINEL, LEYLA, POLAT, AYŞE, ATICI, ŞEBNEM, TAMER, LULUFER, ORAL, UGUR
• Format: Article
• Language: English
• Subjects: 3-aminobenzamide; Animals; apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Bcl-2; Benzamides - pharmacology; endotoxemia; Endotoxemia - physiopathology; Epithelium - drug effects; Epithelium - enzymology; Epithelium - physiopathology; Escherichia coli Infections - physiopathology; Immunohistochemistry; Intestinal Mucosa - drug effects; Intestinal Mucosa - enzymology; Intestinal Mucosa - physiology; Lipopolysaccharides - toxicity; Male; Nitrates - blood; nitric oxide; Nitric Oxide Synthase - antagonists & inhibitors; PARS inhibition; Poly(ADP-ribose) Polymerase Inhibitors; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Rats; Rats, Wistar
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/S1043-6618(02)00075-0

In this lipopolysaccharide (LPS)-induced endotoxemia model, the effects of 3-aminobenzamide (3-AB), a poly(ADP-ribose) synthetase (PARS) inhibitor, on ileal apoptosis were evaluated by light microscopy and M30 cell death staining. Moreover, the relationship between Bcl-2, iNOS expression, and serum nitrate (NO 3 −) levels were investigated. Thirty-two male Wistar rats, weighing 180–220 g were randomly divided into four groups. The group I (control; n=8) received saline and group II (sepsis; n=8) received 10 mg kg −1 LPS intraperitoneally. 3-AB was given to the group IV (S+3-AB; n=8) 20 min before giving LPS and to the group III (C+3-AB; n=8) 20 min before giving saline. Six hours later, blood and ileum samples were taken. Endotoxemic group exhibited significant apoptosis in intestinal epithelial cells and the immunohistochemical examination with M30 was demonstrated that the 3-AB reduced the LPS-induced intestinal apoptosis. Serum NO 3 − level was increased in endotoxemic group, whereas the elevation of NO 3 − level was prevented in LPS+3-AB group ( P