Melatonin and 1400 W ameliorate both intestinal and remote organ injury following mesenteric ischemia/reperfusion.
OBJECTIVE
Acute intestinal ischemia reperfusion (I/R) injury affects not only the intestines but also remote organs due to pro-inflammatory and tissue injurious factors. Thus, we aimed to investigate the roles of melatonin (a powerful antioxidant) and 1400W (a strong inhibitor of inducible nitric oxide) in a rat intestinal I/R injury model, since oxidative and nitrosative injury are believed to be the major causes.


METHODS
A total of 56 Wistar albino rats were used, with seven rats in each group. After I/R induction in the intestines by clamping/unclamping the superior mesenteric artery, we measured malondialdehyde, superoxide dismutase, glutathione peroxidase, nitric oxide, and 3-nitrotyrosine levels in lung, kidney, and liver tissues (to evaluate remote organ injury) as well as in the intestines. Study groups received melatonin, 1400W or both to examine the roles of these molecules in the pathogenesis of injury following I/R.


RESULTS
Melatonin and 1400W had an ameliorating effect on both oxidative and nitrosative stress in the intestine and the lung against mesenteric I/R injury in rats. Moreover, each of these two agents had an inhibitory effect on oxidative injury and histopathological changes in the intestine and the lung. Furthermore, the combination of both agents (melatonin and 1400W) was more effective than either of the agents alone (P < 0.05).


CONCLUSIONS
Melatonin and 1400W, either alone or in combination, were efficient in ameliorating experimental I/R injury of the intestines.
Kesik
Vural
V
Department of Pediatrics, Gulhane Military Medical Academy, Etlik, Ankara, Turkey.
Guven
Ahmet
A
Vurucu
Sabahattin
S
Tunc
Turan
T
Uysal
Bulent
B
Gundogdu
Gokhan
G
Oztas
Emin
E
Korkmaz
Ahmet
A
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D008641:Mesenteric Vascular Occlusion / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D015996:Survival Rate; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
D000578:Amidines; D000975:Antioxidants; D001596:Benzylamines; D004791:Enzyme Inhibitors; C104820:N-(3-(aminomethyl)benzyl)acetamidine; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase; D008550:Melatonin; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat