Reduced activity of antioxidant enzymes underlies contrast media-induced renal injury in volume depletion.
Reduced activity of antioxidant enzymes underlies contrast media-induced renal injury in volume depletion.
复制标题
抗氧化酶活性降低是造影剂引起的血容量不足肾损伤的基础。
DOI：
10.1038/ki.1992.153
复制
发表时间：
1992
影响因子：
19.6
通讯作者：
Beckman,JK
中科院分区：
文献类型：
--
作者：
Yoshioka,T;Fogo,A;Beckman,JK
肾抗氧化酶活性降低是血容量不足时造影剂诱导的肾损伤的基础。氧化剂介导的肾损伤被认为是造影剂引起急性肾功能衰竭的重要机制。由于血容量不足已被认为是造影剂肾病的诱发因素，本研究旨在表征血容量不足期间氧化剂介导的肾损伤的宿主防御机制。比较了急性缺水（WD，72小时）和非缺水大鼠肾皮质抗氧化酶活性。WD大鼠的过氧化氢酶和超氧化物歧化酶活性降低（平均值分别为非WD的48%和60%）。在单独的WD大鼠组中，注射盐水或三种不同造影剂之一，即泛影葡胺/泛影酸钠（DTZ）、碘克酸葡胺/碘克酸钠（IXG）和碘海醇（IHX）。24小时后测量的GFR和肾血浆流速，在注射DTZ的WD大鼠中比注射盐水的WD大鼠低约50%。用IXG和IHX处理的WD大鼠具有与盐水处理的大鼠相似的GFR。在DTZ治疗的WD大鼠，特定产品的膜脂质过氧化，磷脂酰胆碱和磷脂酰乙醇胺氢过氧化物，测定荧光HPLC法，是两倍以上的生理盐水，IXG，或IHX治疗的WD大鼠。DTZ未引起非WD大鼠肾功能不全和脂质过氧化作用增强。因此，DTZ似乎只在WD大鼠中诱导氧化剂介导的损伤。用聚乙二醇偶联过氧化氢酶（1.4mg × 2d）预处理WD大鼠，其皮质过氧化氢酶活性仍保持在与非WD大鼠相似的水平。过氧化氢酶处理的WD大鼠没有出现肾功能损害和DTZ引起的脂质过氧化反应，而热灭活过氧化氢酶或低剂量过氧化氢酶（0.14 mg × 2天）不能预防DTZ引起的肾功能损害。因此，在容量不足，其中局部抗氧化剂水平被压抑，DTZ诱导氧化剂介导的长期肾功能不全和脂质过氧化。
Reduced activity of renal antioxidant enzymes underlies contrast media-induced renal injury in volume depletion. Oxidant-mediated renal injury has been suggested as an important mechanism of acute renal failure induced by contrast media. Since volume depletion has been recognized as a predisposing factor for contrast media nephropathy, the present study was designed to characterize host-defense mechanisms against oxidant-mediated renal injury during volume depletion. Antioxidant enzyme activities in renal cortex were compared between acutely water deprived (WD, 72 hours) and rion-WD rats. WD rats had reduced activities of catalase and superoxide dismutase activities (on average, 48% and 60% of values in non-WD, respectively). In separate groups of WD rats, saline or one of three different contrast media, namely diatrizoate meglumine/diatrizoate sodium (DTZ), ioxaglate meglumine/ioxaglate sodium (IXG), and iohexol (IHX) was injected. Both GFR and renal plasma flow rate, measured 24 hours later, was some 50% less in DTZ-injected than saline-injected WD rats. WD rats treated with IXG and IHX had similar GFR to saline-treated rats. In DTZ-treated WD rats, specific products of membrane lipid peroxidation, phosphatidylcholine and phosphatidylethanolamine hydroperoxide, determined by chemiluminescent HPLC, were more than two-fold higher than saline, IXG, or IHX-treated WD rats. DTZ did not induce renal dysfunction and enhance lipid peroxidation in non-WD rats. Therefore, DTZ appeared to induce oxidant-mediated injury only in WD rats. When WD rats were pretreated with polyethylene glycol-coupled catalase (1.4 mg × 2 days), rerial cortical catalase activity remained at a level similar to that of non-WD rats. Catalase-treated WD rats did not experience renal dysfunction and enhanced lipid peroxidation by DTZ, while heat-inactivated catalase or low dose catalase (0.14 mg × 2 days) failed to prevent DTZ-ihduced renal dysfunction. Thus, in volume depletion, in which local antioxidant levels are depressed, DTZ induced oxidant-mediated prolonged renal dysfunction and lipid peroxidation.