The role of recombinant human erythropoietin in lipid peroxidation and platelet-activating factor generation in a rat model of necrotizing enterocolitis.
In the present study we examined the effect of recombinant human erythropoietin (rhEPO) on intestinal malondialdehyde (MDA) as an index of lipid peroxidation, related to iron-catalysed free radical reaction and platelet-activating factor (PAF) synthesis in the experimental model of necrotizing enterocolitis (NEC). Three groups, each consisting of eight 1-day-old Wistar albino rat pups, were studied; Group 1, hypoxia-reoxygenation; Group 2, hypoxia-reoxygenation and rhEPO pretreatment; Group 3, control. rhEPO was given 750 U/kg/week by intraperitoneal injection three times a week for 2 weeks. On day 15th of life, hypoxia was induced by placing rat pups in a 100% CO2 chamber for 5 min. After hypoxia, the rat pups were reoxygenated for 10 min with 100% oxygen and returned to their mothers. All pups were killed at 4h following hypoxia-reoxygenation. The abdomen was opened and representative samples of injured areas were taken for histopathologic examination. MDA and PAF levels were determined in the intestine. Significantly increased intestinal MDA content was found in Group 1 rat pups compared to Group 2 and Group 3 pups (p < 0.001 and p < 0.001, respectively). However, PAF concentrations were highly elevated in the intestine of Group 1 and Group 2 pups (p>0.05) when compared to the intestine of Group 3 pups (p < 0.001 and p < 0.001, respectively). Histopathologic findings did not differ between Groups 1 and 2. The present study demonstrates that oxygen-derived free radicals and PAF are involved in the pathophysiological mechanism of the development of NEC. This study also shows that administration of rhEPO significantly decreases lipid peroxidation; however, PAF generation was not inhibited in hypoxia-induced bowel necrosis.
Akisu
M
M
Department of Pediatrics, Ege University Medical School, Izmir, Turkey. makisu@med.ege.edu.tr
Küllahçioğlu Girgin
F
F
Baka
M
M
Hüsseyinov
A
A
Kültürsay
N
N
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy* / Q000503:physiopathology*; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000187:drug effects* / Q000378:metabolism; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D004921:Erythropoietin; D008315:Malondialdehyde