title: The role of poly(ADP-ribose) synthetase inhibition on the intestinal mucosal barrier after thermal injury.
abstract: Oxidative and nitrosative stressor agents can trigger DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) synthetase (PARS). Activation of the enzyme depletes the intracellular concentration of energetic substrates such as nicotinamide adenine dinucleotide (NAD). This process can result in cell dysfunction and cell death. PARS inhibitors have been successfully used in ischemia-reperfusion injury, inflammation and sepsis in several experimental models. In our experimental study, we investigated the role of 3-aminobeanzamide (3-AB), a non-specific PARS inhibitor, on the intestinal mucosal barrier after burn injury. Twenty-four Wistar rats were randomly divided into three groups. The sham group (n = 8) was exposed to 21 degrees C water while the burn group (n = 8) and the burn + 3-AB group (n = 9) were exposed to boiling water for 12s to produce a full thickness burn in 35-40% of total body surface area. In the burn + 3-AB group, 10mg/kg of 3-AB was given intraperitoneally 10min before thermal injury. Twenty-four hours later, tissue samples from mesenteric lymph nodes (MLN), spleen and liver were obtained under sterile conditions for microbiological analysis and ileum samples were obtained for biochemical and histopathological analysis. In burn group, the incidence of bacteria isolated from MLN and spleen was significantly higher than other groups (P < 0.05). 3-AB pre-treatment prevented burn induced bacterial translocation and it significantly reduced burn induced intestinal injury. Tissue malondialdehyde and 3-nitrotyrozine levels were found significantly lower than that of the burn group. These data suggest that the relationship between PARS pathway and lipid peroxidation in intestinal tissue and PARS has a role in intestinal injury caused by thermal injury.
authors.affiliation: Department of Pediatric Surgery, Faculty of Medicine, Mersin University, Tip Fakültesi Hastanesi, Zeytinlibahçe C, 33070 Mersin, Turkey. dinceravlan@yahoo.com
authors.forename: Dinçer
authors.initials: D
authors.lastname: Avlan
authors.forename: Hakan
authors.initials: H
authors.lastname: Taşkinlar
authors.forename: Ali
authors.initials: A
authors.lastname: Unlü
authors.forename: Candan
authors.initials: C
authors.lastname: Oztürk
authors.forename: Leyla
authors.initials: L
authors.lastname: Cinel
authors.forename: Ali
authors.initials: A
authors.lastname: Nayci
authors.forename: Ismail
authors.initials: I
authors.lastname: Cinel
authors.forename: Selim
authors.initials: S
authors.lastname: Aksöyek
mesh_terms: D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D002056:Burns / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000382:microbiology; D008198:Lymph Nodes / Q000382:microbiology; D008315:Malondialdehyde / Q000032:analysis; D008643:Mesentery / Q000382:microbiology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000382:microbiology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; C025160:3-aminobenzamide