Effects of omeprazole and gentamicin on the biochemical and histopathological alterations of the hypoxia/ reoxygenation induced intestinal injury in newborn rats.
We utilized a newborn rat model of hypoxia/reoxygenation (H/R) that resembles human necrotizing enterocolitis (NEC) to investigate the effects of omeprazole and/or gentamicin on the formation of free oxygen radicals (FOR) and bowel histopathology. For H/R, 1-day-old rats were placed into a chamber of 100% CO2 for 5 min, then they were reoxygenized for the next 5 min. The rats (n = 70) were divided into seven groups: group 1 (control), group 2 (H/R), group 3 (omeprazole), group 4 (H/R + omeprazole), group 5 (gentamicin), group 6 (H/R + gentamicin), group 7 (H/R + omeprazole + gentamicin). Gentamicin and/or omeprazole were given orally for 3 days, then all animals were killed; bowel specimens were harvested. Histopathologic injury scores (HIS) and malonyldialdehyde (MDA) and XO/(XO+XDH) rates (XO; xanthine oxidase, XDH; xanthine dehydrogenase) were measured, which reflect the FOR levels. In group 2, the HIS was significantly higher than groups 4 and 6. The mean MDA values in groups 1-7 were as follows: 54.16, 104.2, 56.85, 63.43, 62.31, 76.85, 79.13, respectively. The mean XO/(XO + XDH) levels were 0.306, 0.461, 0.286, 0.335, 0.323, 0.410, 0.375 from groups 1 -7, respectively. Group 2 rats had significantly more MDA and XO/(XO + XDH) rates versus other groups (P < 001). Histopathologic injury and biochemical results were significantly more severe in group 2 than in groups 4 and 6 (P < 001). There was no difference between groups 1 and 4 according to XO/(XO + XDH) rates. In newborn rats, H/R produces FOR, which cause serious intestinal damage. Omeprazole and/or gentamicin reduce biochemical and histopathologic bowel damage. This effect was more obvious in omeprazole treated rats. We think omeprazole may open new insights into the treatment of H/R related bowel injuries like NEC.
Biçakçi
Unal
U
Department of Pediatric Surgery, Ondokuz Mayis University, Kurupelit, 55139 Samsun, Turkey.
Tander
Burak
B
Aritürk
Ender
E
Aydin
Birsen Kiliçoğlu
BK
Aydin
Oğuz
O
Rizalar
Riza
R
Eren
Zafer
Z
Bernay
Ferit
F
D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000378:metabolism / Q000473:pathology*; D005609:Free Radicals / Q000032:analysis; D005839:Gentamicins / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology*; D008315:Malondialdehyde / Q000032:analysis; D009853:Omeprazole / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014968:Xanthine Dehydrogenase / Q000032:analysis; D014969:Xanthine Oxidase / Q000032:analysis
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D005609:Free Radicals; D005839:Gentamicins; D008315:Malondialdehyde; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D009853:Omeprazole