Effects of esomeprazole magnesium on nonsteroidal anti-inflammatory drug gastropathy
Effects of esomeprazole magnesium on nonsteroidal anti-inflammatory drug gastropathy
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DOI：
10.1007/s10620-005-1283-z
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发表时间：
2005-01-01
影响因子：
3.1
通讯作者：
Opara, EC
中科院分区：
文献类型：
--
作者：
Koch, TR;Petro, A;Opara, EC
有人提出，非甾体类抗炎药引起的组织损伤与组织自由基产生增加和抗氧化剂消耗有关。我们已经证明，埃索美拉唑增加小鼠胃的总抗氧化能力，因此，假设埃索美拉唑的保护作用，在治疗过程中与非甾体抗炎药是与胃的抗氧化能力增加，减少组织自由基的产生。A/J小鼠通过每日管饲法接受四种治疗之一：溶剂中的盐水（对照）、吲哚美辛、埃索美拉唑或吲哚美辛和埃索美拉唑。10天后，处死所有小鼠，并使用经验证的测定法测量胃总抗氧化能力、脂质过氧化物水平和髓过氧化物酶活性。吲哚美辛治疗的小鼠出现体重减轻和黑便。接受吲哚美辛和埃索美拉唑的小鼠没有死亡，但接受吲哚美辛的小鼠死亡率为38%（chi（2），p = 0.05）。与埃索美拉唑和吲哚美辛治疗相比，接受吲哚美辛治疗的小鼠胃过氧化脂质水平增加（P = 0.03）。与接受吲哚美辛的小鼠相比，接受埃索美拉唑和吲哚美辛的小鼠胃总抗氧化能力有明显增加的趋势（P = 0.08）。胃髓过氧化物酶活性在四组之间没有差异。埃索美拉唑显着改善生存小鼠接受吲哚美辛，减少自由基的产生，估计过氧化脂质水平，并出现增加胃总抗氧化能力。埃索美拉唑治疗胃病的有益作用机制比以前认为的更复杂。
It has been proposed that tissue damage induced by nonsteroidal anti-inflammatory drugs is related to increased tissue free radical production with antioxidant depletion. We have shown that esomeprazole increases gastric total antioxidant capacity in mice and, therefore, hypothesized that the protective effect of esomeprazole during treatment with a nonsteroidal anti-inflammatory drug is related to increased gastric antioxidant capacity and decreased tissue free radical production. A/J mice received one of four treatments by daily gavage: saline in vehicle (control), indomethacin, esomeprazole, or indomethacin and esomeprazole. After 10 days, all mice were sacrificed and validated assays were used to measure gastric total antioxidant capacity, lipid peroxide levels, and myeloperoxidase activity. Indomethacin-treated mice developed weight loss and melena. No mice receiving indomethacin and esomeprazole died, but the death rate while receiving indomethacin was 38% (chi(2), p = 0.05). Gastric lipid peroxide levels increased in mice receiving indomethacin treatment compared to treatment with esomeprazole and indomethacin (P = 0.03). There was a strong trend (P = 0.08) toward increased gastric total antioxidant capacity in mice receiving esomeprazole and indomethacin compared to mice receiving indomethacin. Gastric myeloperoxidase activities were not different among the four groups. Esomeprazole significantly improved survival in mice that received indomethacin, reduced free radical production, as estimated by lipid peroxide levels, and appeared to increase gastric total antioxidant capacity. The mechanisms for the beneficial effects of esomeprazole in the treatment of gastropathy are more complex than previously thought.