Protective effects of vitamin E and omeprazole on the hypoxia/reoxygenation induced intestinal injury in newborn rats

Abstract

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.

Medical ozone therapy reduces oxidative stress and intestinal damage in an experimental model of necrotizing enterocolitis in neonatal rats

“…In experimental models of NEC, administration of agents that either inhibits ROS production or acts as antioxidant has been shown to reduce tissue damage [2,3,7,8]. It was also reported that MDA increases and SOD decreases in intestinal tissue hypoxia/reoxygenation-induced intestinal injury in newborn rats [9,26,33], and our results are consistent with these previous works [4].…”

Omeprazole Attenuates Hyperoxic Lung Injury in Mice via Aryl Hydrocarbon Receptor Activation and Is Associated with Increased Expression of Cytochrome P4501A Enzymes

“…Thus, it is plausible that the antioxidant properties of omeprazole may be beneficial in other pathologic conditions associated with oxidative damage (Halliwell et al, 2000;Hanauer, 2006). Omeprazole has also been shown to protect against necrotizing enterocolitis in newborn rats subjected to hypoxia/reoxygenation (Cadir et al, 2008). All of these data show that omeprazole has antioxidant and anti-inflammatory properties.…”

The development of animal models for the study of necrotizing enterocolitis

“…roles of pro-inflammatory cytokines in the development of NEC (Seitz et al, 2005), the roles of enterocyte migration in the resolution of NEC (Cetin et al, 2004), and the protective effects of various agents including: maternal cortisol (Israel et al, 1990), intestinal trefoil factor (Guthmann and Kluthe, 2007;Shi et al, 2007), vitamin E (Cadir et al, 2008), captopril (Zani et al, 2008), polyunsaturated fatty acid supplementation , the inhibition of NF-κB (De Plaen et al, 2007), administration of pentoxifylline (Travadi et al, 2006), granulocyte colony stimulating factor (Canpolat et al, 2006), arginine (Shah and Shah, 2007) and anti-TNF-α (Halpern et al, 2006). Taken together, these studies illustrate the important role that the rat model has played in advancing our understanding of NEC pathogenesis and in devising novel therapeutic approaches for this disease.…”