Poly (adp-ribose) synthetase inhibition reduces oxidative and nitrosative organ damage after thermal injury.
Poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme activated by DNA single-strand breakage, which can be triggered by reactive oxygen and nitrogen species. Activation of this enzyme depletes the intracellular concentration of energetic substrates such as nicotinamide adenine dinucleotide (NAD). Eventually, this process results in cell dysfunction and cell death. PARS inhibitors have successfully shown benefits in several experimental models of ischemia-reperfusion injury, inflammation, and sepsis. In our experimental study, we investigated the role of 3-aminobenzamide (3-AB), a nonspecific PARS inhibitor, in systemic organ damage after burn. Twenty-four Wistar rats were randomly divided into three groups. The sham group (n=8) was exposed to 21 degrees C water, and the burn group (n=8) and the burn-plus-3-AB group (n=8) were exposed to boiling water for 12 s to produce a full-thickness burn of 35-40% of total body surface area. In the burn-plus-3-AB group, 3-AB 10 mg/kg was given intraperitoneally 10 min before thermal injury. Twenty-four hours later, tissue samples were obtained for biochemical analysis from lung, intestine, and kidney. In the burn group, tissue malondialdehyde, myeloperoxidase, and 3-nitrotyrosine levels in all organs were significantly increased compared with the sham group (p<0.05). Pretreatment with 3-AB significantly reduced burn-induced organ damage (p<0.05). These data provide evidence of the relationship between the PARS pathway and lipid peroxidation in systemic organ damage after thermal injury.
Avlan
Dinçer
D
Department of Paediatric Surgery, Faculty of Medicine, Mersin University, Tip Fakültesi Hastanesi, Zeytinlibahçe C, 33070 Mersin, Turkey. dinceravlan@yahoo.com
Unlü
Ali
A
Ayaz
Lokman
L
Camdeviren
Handan
H
Nayci
Ali
A
Aksöyek
Selim
S
D000818:Animals; D001549:Benzamides / Q000627:therapeutic use*; D002056:Burns / Q000188:drug therapy / Q000503:physiopathology*; D015227:Lipid Peroxidation / Q000502:physiology; D008315:Malondialdehyde; D009195:Peroxidase / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D017208:Rats, Wistar
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D008315:Malondialdehyde; C025160:3-aminobenzamide; D009195:Peroxidase