The role of poly(ADP-ribose) synthetase inhibition in preventing endotoxemia-induced intestinal epithelial apoptosis.
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 180-220g 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<0.05). The increased iNOS expression observed in the LPS group was also prevented by 3-AB. Compared with the endotoxemic group, ileal epithelial columnar cells from LPS+3-AB group had a dense Bcl-2 staining which was almost identical with control. In conclusion, 3-AB decreases LPS-induced apoptosis in ileum by preventing LPS-induced depletion of Bcl-2 and blocking iNOS gene. Modification of Bcl-2 expression by PARS inhibitors should further be investigated as a new therapeutic alternatives in septic states.
Cinel
Ismail
I
Department of Anesthesiology and Reanimation, Mersin University Faculty of Medicine, Adnan Menderes Bulvari, Marina Sitesi, C Blok, No: 4, Mersin, Turkey. cinelismail@yahoo.com
Buyukafsar
Kanso
K
Cinel
Leyla
L
Polat
Ayşe
A
Atici
Sebnem
S
Tamer
Lulufer
L
Oral
Ugur
U
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001549:Benzamides / Q000494:pharmacology*; D019446:Endotoxemia / Q000503:physiopathology*; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D004927:Escherichia coli Infections / Q000503:physiopathology*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D001549:Benzamides; D008070:Lipopolysaccharides; D009566:Nitrates; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; C025160:3-aminobenzamide; D019001:Nitric Oxide Synthase