Inhibition of poly(ADP-ribose) polymerase attenuates lung tissue damage after hind limb ischemia-reperfusion in rats.

Abstract

The objective of this study was to investigate the effects of 3-aminobenzamide (3-AB) on tissue damage in lung after hind limb ischemia-reperfusion (I/R), by assessing blood biochemical assay and histopathological analysis. Thirty-five adult Wistar rats were divided into five groups. After application of anaesthesia both hind limbs were occluded with tourniquets. Following ischemia period for 60 min, the tourniquets were removed allowing reperfusion for 120 min. The IR group received 0.5 ml of saline while the IR+AB group received 3-AB (10 mgkg(-1) intraperitoneally). The IR+DMSO group was given 0.5 ml 10% DMSO 30 min before the removal of the tourniquets. The control group received 0.5 ml saline and the AB group received 0.5 ml 3-AB (10 mgkg(-1)) intraperitoneally. At the end of the reperfusion period, mid-line sternotomy was performed. Blood samples were taken with cardiac puncture. Bronchoalveolar lavage (BAL) of the left lung was performed with saline. Right lung was preserved for histopathological evaluation and biochemical examination. Lung tissue malondialdehyde (MDA) and 3-nitrotyrosine levels, myeloperoxidase and Na+/K+ ATP-ase activities, wet to dry weight ratios, and plasma and BAL fluid MDA levels were determined. Histopathological evaluation was performed, too. Hind limb IR caused significant increase in the lung tissue 3-NT to total tyrosine ratio (p = 0.014), wet to dry weight ratio (p = 0.000), MPO activity (p = 0.000), and MDA levels (p = 0.000). The animals treated with 3-AB showed a statistically significant decrease in these values (p < 0.05). Na+/K+ ATP-ase activity which was found to be decreased significantly with IR, returned to near normal levels with 3-AB treatment. Additionally, lung tissue injury in IR group characterized with moderate interstitial congestion and neutrophil infiltration, showed remarkable amelioration following 3-AB treatment. Our results strongly support the view that poly(ADP-ribose) polymerase (PARP) plays an important role in the inflammatory process in hind limb I/R-induced lung injury and as a PARP inhibitor, 3-AB seems to have a potential to treat this inflammatory injury.

• Authors: Oguz Koksel, Caglar Yildirim, Leyla Cinel, Lulufer Tamer, Ali Ozdulger, Mine Bastürk, Ulas Degirmenci, Arzu Kanik, Ismail Cinel
• Journal: Pharmacological research (Pharmacol Res) Vol. 51 Issue 5 Pg. 453-62 (May 2005) ISSN: 1043-6618 [Print] Netherlands
• PMID: 15749460 (Publication Type: Journal Article)

Chemical References

• Benzamides
• Enzyme Inhibitors
• Poly(ADP-ribose) Polymerase Inhibitors
• Reactive Nitrogen Species
• Reactive Oxygen Species
• benzamide
• 3-aminobenzamide

Topics

• Animals
• Benzamides (pharmacology)
• Cell Membrane (metabolism)
• Enzyme Inhibitors (pharmacology)
• Female
• Hindlimb (blood supply)
• Lipid Peroxidation
• Lung (drug effects, metabolism, pathology)
• Lung Diseases (etiology, metabolism, pathology)
• Neutrophils (pathology)
• Poly(ADP-ribose) Polymerase Inhibitors
• Pulmonary Edema (pathology)
• Rats
• Rats, Wistar
• Reactive Nitrogen Species (biosynthesis)
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (complications, pathology)