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Evaluation of prophylactic effects of omeprazole and/or vitamin E on the formation of free oxygen radicals (FOR) and bowel histopathology in the newborn rat model of hypoxia/reoxygenation (H/R) that resembles human necrotizing enterocolitis (NEC). Eighty newborn rats were randomly divided into eight groups. H/R was done using airtight chamber. Rats were exposed to 100% CO2 for 15 min followed by a reoxygenation for the next 15 min with 100% O2. Group 1 (n = 10) was the control group. Group 2 (n = 10) rats received vitamin E. In Group 3 (n = 10) omeprazole was administrated. Group 4 (n = 10) rats received omeprazole and vitamin E. Group 5 (n = 10) rats were subjected to H/R two times for 2 days and one time for 3 days. Group 6 (n = 10) received vitamin E in addition to H/R for 5 days and in Group 7 (n = 10) omeprazole in addition to H/R for 5 days. In Group 8 (n = 10), vitamin E and omeprazole and H/R were applied for 5 days. Rats were killed at the end of the each process and bowel specimens were harvested for histopathological and biochemical investigations. We administrated vitamin E intramuscularly 300 unit/kg per day and omeprazole orally 20 mg/kg per day. Malondialdehyde (MDA), xanthine oxidase (XO), xanthine dehydogenase (XDH) and XO/(XO + XDH) were measured. Vitamin E and/or omeprazole treated rats had significantly less XO% levels than H/R only group (0.36, 0.38 and 0.57, respectively). Similarly, the MDA levels were significantly lower in vitamin E and/or omeprazole received rats than H/R only rats (88.8, 97.9 and 122.6, respectively). All rats treated with omeprazole and/or vitamin E had better biochemical and histopathological levels compared to H/R rats (p < 0.05). Histopathological results show that Group 5 (H/R only) had significantly more intestinal damage when compared with Group 6 (vitamin E + H/R), Group 7 (omeprazole + R/H) and Group 8 (vitamin E + omeprazole + H/R) (p < 0.001). Grade 2 and 3 intestinal damages were only in Group 5 and there were no statistical difference between in Groups 6, 7 and 8 (p > 0.001). Omeprazole and/or vitamin E may protect the biochemical and histopathological intestinal damage of H/R injury in rats. These drugs may be beneficial in the prophylaxis of NEC in humans as well.

The aim of the study reported here was to evaluate the biochemical and histopathologic effects of omeprazole and vitamin E in rats with corrosive esophageal burns. A total of 144 Wistar Albino rats were divided into 12 experimental groups (12 rats per group) and used in an animal study. Group I rats were given a laparotomy and received no treatment (control group), while groups II, III and IV received a laparotomy and were treated with omeprazole, vitamin E or omeprazole/vitamin E, respectively. Groups V-XII rats received a laparotomy and were given a caustic acid burn through acid instillation (1 ml caustic 10% sulphuric acid; groups V-VIII) or alkali instillation (corrosive 10% sodium hydroxide solution; groups IX-XII) into the isolated esophageal segment via a 22-Fr cannula for 2 min. Each group of rats subjected to caustic burn received either no treatment (groups V and IX) or were treated with omeprazole, vitamin E or omeprazole/vitamin E, respectively (remaining six groups). Omeprazole (20 mg/kg) or vitamin E (10 mg/kg) was administered to the rats intraperitoneally or intramuscularly, respectively. Seventy-two rats (50% of each group, n = 6) were killed immediately after the experimental treatment (acute phase). The remaining rats were kept under standard conditions for 21 days (late phase) before being killed. The distal esophageal segments were harvested from all animal and used in histopathologic and biochemical analyses. Compared to the controls (no caustic burn), rats receiving only the acid or alkali installation (and no subsequent treatment) had the highest mean malondialdehyde (16.9 and 15.8 micromol MDA/g protein, respectively) and hydroxyproline (5.9 and 5.7; mg HP/g wet tissue) levels of all groups. In comparison, rats treated with acid + omeprazole and/or vitamin E had relatively lower MDA (12.9 and 11.6 micromol/g protein, respectively) and HP levels (4.3 and 4.08 mg/g wet tissue, respectively). Similarly, rats treated with alkali + omeprazole and/or vitamin E had low levels of MDA (13.9 and 11.7 micromol/g protein, respectively) and HP (4.3 and 4.4 mg/g wet tissue, respectively). The glutathione (GSH) levels of acid-only- or alkali-only-treated rats were lower than those found in omeprazole- and/or vitamin E-treated rats. Based on these results, we conclude that vitamin E and omeprazole affect the biochemical and histopathologic parameters in rats receiving corrosive esophageal burn from acid and alkali. The effect of both substances was slightly greater in the acid-treated groups.

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.