Jotti A, Maiorino M, Paracchini L, Piccinini F, Ursini F
Institute of Applied Pharmacology, University of Milan, Italy.
Free Radic Biol Med. 1994 Feb;16(2):283-8. doi: 10.1016/0891-5849(94)90154-6.
The involvement of Se enzymes in the protection against the oxidative stress induced by adriamycin (ADR) in rat heart has been studied in animals fed for 10 weeks at three different levels of Se content (low = 0.02 ppm; normal = 0.5 ppm; high = 1.0 ppm) and receiving a weekly injection of 3 mg/kg ADR for 4 weeks. ECG (QaT duration) and contractility of isolated atria were measured. The high-Se diet showed a significant protection on both parameters. To assess the hypothesis that an increase of specific activity of antioxidant Se enzymes may account for the cardioprotective effect of selenium, glutathione peroxidase (GPX), and phospholipid hydroperoxide glutathione peroxidase (PHGPX) were tested. The assays were performed on ventricles isolated from treated rats. At the end of the experimental period, GPX (cytosolic enzyme) did not show any significant difference between controls and ADR-treated at any level of Se content, thus excluding its involvement in the cardioprotection observed in high-Se ADR-treated animals. PHGPX, which is present both in cytosol and in the cell membrane, showed a trend to increase its activity in the presence of ADR treatment only in the membrane fraction; however, the statistical significance was reached only in the low-Se group (+100%). This observation suggests that membrane PHGPX might be involved in the cellular mechanism of adaptation of the heart to the toxic effects of ADR; however, the behavior of these enzymes does not seem to account for the significant protection of selenium supplementation both on ECG and on contractile indices of ADR cardiotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了硒酶在大鼠心脏中对阿霉素（ADR）诱导的氧化应激的保护作用。将动物分为三组，分别饲喂含三种不同硒水平（低 = 0.02 ppm；正常 = 0.5 ppm；高 = 1.0 ppm）的饲料10周，并每周注射3 mg/kg ADR，持续4周。测量心电图（QaT间期）和离体心房的收缩性。高硒饮食对这两个参数均有显著保护作用。为了评估抗氧化硒酶比活性增加可能是硒心脏保护作用的原因这一假设，检测了谷胱甘肽过氧化物酶（GPX）和磷脂氢过氧化物谷胱甘肽过氧化物酶（PHGPX）。检测在从处理过的大鼠分离出的心室上进行。在实验期结束时，在任何硒含量水平下，GPX（胞质酶）在对照组和ADR处理组之间均未显示出显著差异，因此排除了其参与高硒ADR处理动物中观察到的心脏保护作用。PHGPX存在于胞质和细胞膜中，仅在膜部分中，ADR处理使其活性有增加的趋势；然而，仅在低硒组达到统计学显著性（增加100%）。这一观察结果表明，膜PHGPX可能参与心脏对ADR毒性作用的细胞适应机制；然而，这些酶的行为似乎并不能解释补充硒对ADR心脏毒性的心电图和收缩指标的显著保护作用。（摘要截断于250字）
