Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.1.4 (xanthine dehydrogenase)
 1,236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Effects of omeprazole and gentamicin on the biochemical and histopathological alterations of the hypoxia/ reoxygenation induced intestinal injury in newborn rats. 1620 29

Proton pump inhibitors (PPIs) are widely used drugs that may increase the cardiovascular risk by mechanisms not entirely known. While PPIs increase asymmetric dimethylarginine (ADMA) levels and inhibit nitric oxide production, it is unknown whether impaired vascular redox biology resulting of increased xanthine oxidoreductase (XOR) activity mediates PPIs-induced endothelial dysfunction (ED). We examined whether increased XOR activity impairs vascular redox biology and causes ED in rats treated with omeprazole. We also examined whether omeprazole aggravates the ED found in hypertension. Treatment with omeprazole reduced endothelium-dependent aortic responses to acetylcholine without causing hypertension. However, omeprazole did not aggravate two-kidney, one-clip (2K1C) hypertension, nor hypertension-induced ED. Omeprazole and 2K1C increased vascular oxidative stress as assessed with dihydroethidium (DHE), which reacts with superoxide, and by the lucigenin chemiluminescence assay. The selective XOR inhibitor febuxostat blunted both effects induced by omeprazole. Treatment with omeprazole increased plasma ADMA concentrations, XOR activity and systemic markers of oxidative stress. Incubation of aortic rings with ADMA increased XOR activity, DHE fluorescence and lucigenin chemiluminescence signals, and febuxostat blunted these effects. Providing functional evidence that omeprazole causes ED by XOR-mediated mechanisms, we found that febuxostat blunted the ED caused by omeprazole treatment. This study shows that treatment with omeprazole impairs the vascular redox biology by XOR-mediated mechanisms leading to ED. While omeprazole did not further impair hypertension-induced ED, further studies in less severe animal models are warranted. Our findings may have major relevance, particularly to patients with cardiovascular diseases taking PPIs.
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PMID:Omeprazole impairs vascular redox biology and causes xanthine oxidoreductase-mediated endothelial dysfunction. 2752 59