Huang S H, Leonard S, Shi X, Goins M R, Vallyathan V
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA.
Free Radic Biol Med. 1998 Mar 1;24(4):529-36. doi: 10.1016/s0891-5849(97)00285-2.
Lazaroids (21-amino steroids) are believed to be powerful scavengers of reactive oxygen species (ROS) and inhibitors of lipid peroxidation. Crystalline silica, a potent cytotoxic agent, causes pulmonary fibrosis in experimental animals and humans. ROS have been previously shown to be involved in crystalline silica-induced pulmonary injury and inflammation. In the present study, the reaction rate of lazaroid (U-75412E) with hydroxyl radical (.OH) generated by Fenton reaction (Fe(II) + H2O2 --> Fe(III) + OH- + .OH) was investigated using ESR spin-trapping competition reactions. The reaction rate constant was found to be 1.0 x 10(10) M(-1)s(-1), which was comparable with those of other efficient .OH radical scavengers. As indicators of crystalline silica-induced cytotoxicity and its protection by this antioxidant lazaroid (U-75412E) we measured lactate dehydrogenase, N-acetyl-beta-glucosaminidase, superoxide dismutase, glutathione peroxidase, and hydrogen peroxide released from rat alveolar macrophages. Lipid peroxidation, a prominent manifestation of .OH radical-induced cell injury, was also measured to evaluate the protective value of lazaroid. Alveolar macrophages treated with lazaroid (U-75412E) before crystalline silica exposure were protected against cell injury and lipid peroxidation as demonstrated by those indicators. Lazaroid (U-75412E) scavenges .OH radicals generated by crystalline silica-mediated reaction from H2O2 and inhibits lipid peroxidation in macrophages induced by these particles.
拉扎oids（21-氨基类固醇）被认为是活性氧（ROS）的强力清除剂和脂质过氧化的抑制剂。结晶二氧化硅是一种强效细胞毒性剂，可在实验动物和人类中引起肺纤维化。先前已表明ROS参与结晶二氧化硅诱导的肺损伤和炎症。在本研究中，使用电子自旋共振（ESR）自旋捕获竞争反应研究了拉扎oid（U-75412E）与芬顿反应（Fe（II）+ H2O2→Fe（III）+ OH- +·OH）产生的羟基自由基（·OH）的反应速率。发现反应速率常数为1.0×10（10）M（-1）s（-1），与其他高效·OH自由基清除剂的反应速率常数相当。作为结晶二氧化硅诱导的细胞毒性及其被这种抗氧化拉扎oid（U-75412E）保护的指标，我们测量了大鼠肺泡巨噬细胞释放的乳酸脱氢酶、N-乙酰-β-葡萄糖苷酶、超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢。脂质过氧化是·OH自由基诱导的细胞损伤的一个突出表现，也被测量以评估拉扎oid的保护价值。如这些指标所示，在暴露于结晶二氧化硅之前用拉扎oid（U-75412E）处理的肺泡巨噬细胞免受细胞损伤和脂质过氧化的影响。拉扎oid（U-75412E）清除由结晶二氧化硅介导的反应从H2O2产生的·OH自由基，并抑制这些颗粒诱导的巨噬细胞中的脂质过氧化。
