Erdosteine and ebselen as useful agents in intestinal ischemia/reperfusion injury.
BACKGROUND
Reactive oxygen and nitrogen species generated during reperfusion of the tissue are characteristic of ischemia/reperfusion (I/R) injury. The purpose of the present study was to investigate whether erdosteine and ebselen, molecules with antioxidant properties and peroxynitrite scavenging capability, respectively, can reduce oxidative stress and histological damage in the rat small bowel subjected to mesenteric I/R injury.


METHODS
Forty Sprague-Dawley rats were divided into five groups equally: sham, I/R, I/R plus erdosteine, I/R plus ebselen, and I/R plus erdosteine and ebselen. Intestinal ischemia for 45 min and reperfusion for 3 d were carried out. Ileal specimens were obtained to determine the tissue levels of malondialdehide (MDA), protein carbonyl content (PCC), superoxide dismutase (SOD), glutathione peroxidase (GPx), nitrite/nitrate (NO(x)) level and histological changes.


RESULTS
Intestinal I/R resulted in increased tissue MDA, PCC, and NO(x) levels and decreased SOD and GPx activities. Both erdosteine and ebselen alone significantly decreased MDA, PCC, and NO(x) levels and increased antioxidant enzymes activities, but all values were different from control. These changes almost returned to control values in the group treated with erdostein and ebselen. Histopathologically, the intestinal injury in rats treated with erdosteine and ebselen as well as combination were less than I/R group.


CONCLUSIONS
Both erdosteine and ebselen were able to attenuate I/R injury of the intestine via inhibition of lipid peroxidation and protein oxidation, maintenance of antioxidant, and free radical scavenger properties. Nevertheless, combination treatment showed more promising results, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing intestinal I/R injury.
Tunc
Turan
T
Department of Pediatrics, Gulhane Military Medical Academy, Etlik, Ankara, Turkey.
Uysal
Bulent
B
Atabek
Cuneyt
C
Kesik
Vural
V
Caliskan
Bahadir
B
Oztas
Emin
E
Ersoz
Nail
N
Oter
Sukru
S
Guven
Ahmet
A
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001393:Azoles / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007421:Intestine, Small / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D054833:Isoindoles; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D023421:Models, Animal; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000502:physiology; D050050:Protein Carbonylation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D013864:Thioglycolates / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*
D000975:Antioxidants; D001393:Azoles; D015415:Biomarkers; D054833:Isoindoles; D009566:Nitrates; D009573:Nitrites; D016566:Organoselenium Compounds; D013864:Thioglycolates; D013876:Thiophenes; C042986:ebselen; D008315:Malondialdehyde; C048498:erdosteine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase