Palma J M, Garrido M, Rodríguez-García M I, del Río L A
Unidad de Bioquímica Vegetal, Estación Experimental del Zaidín, C.S.I.C., Granada, Spain.
Arch Biochem Biophys. 1991 May 15;287(1):68-74. doi: 10.1016/0003-9861(91)90389-z.
The existence of a relationship between clofibrate-induced peroxisome proliferation and oxidative stress mediated by activated oxygen species was studied in intact peroxisomes purified from Pisum sativum L. plants. Incubation of leaves with 1 mM clofibrate produced a remarkable increase in the peroxisomal activity of acyl-CoA oxidase and, to a lesser extent, of xanthine oxidase, whereas there was a nearly complete loss of catalase activity and a decrease in Mn-superoxide dismutase. Ultrastructural studies of intact leaves showed that clofibrate induced a five- and twofold proliferation of the peroxisomal and mitochondrial populations, respectively, in comparison with those in control leaves. Prolonged incubation with clofibrate produced considerable alterations in the ultrastructure of cells. In peroxisomal membranes, the NADH-induced generation of O2- radicals, as well as the lipid peroxidation of membranes, increased as a result of treatment of plants with clofibrate. In intact peroxisomes treated with this hypolipidemic drug, the H2O2 concentration was higher than in peroxisomes from control plants. These results demonstrate that clofibrate stimulates the production of activated oxygen species (O2- and H2O2) inside peroxisomes, as well as the lipid peroxidation of peroxisomal membranes. This effect is concomitant with a decrease of catalase and Mn-SOD activities, the main peroxisomal enzymatic defenses against H2O2 and O2-, and indicates that in the toxicity of clofibrate, at the level of peroxisomes, an oxidative stress mechanism mediated by activated oxygen species is involved.
在从豌豆植株中纯化得到的完整过氧化物酶体中，研究了氯贝丁酯诱导的过氧化物酶体增殖与活性氧介导的氧化应激之间的关系。用1 mM氯贝丁酯处理叶片后，酰基辅酶A氧化酶的过氧化物酶体活性显著增加，黄嘌呤氧化酶的活性也有一定程度的增加，而过氧化氢酶活性几乎完全丧失，锰超氧化物歧化酶活性降低。对完整叶片的超微结构研究表明，与对照叶片相比，氯贝丁酯分别使过氧化物酶体和线粒体数量增加了5倍和2倍。用氯贝丁酯长时间处理会导致细胞超微结构发生显著变化。在用氯贝丁酯处理植物后，过氧化物酶体膜中NADH诱导的O2-自由基生成以及膜的脂质过氧化作用均增加。在用这种降血脂药物处理的完整过氧化物酶体中，H2O2浓度高于对照植物的过氧化物酶体。这些结果表明，氯贝丁酯刺激过氧化物酶体内活性氧（O2-和H2O2）的产生以及过氧化物酶体膜的脂质过氧化。这种效应伴随着过氧化氢酶和锰超氧化物歧化酶活性的降低，而过氧化氢酶和锰超氧化物歧化酶是过氧化物酶体对抗H2O2和O2-的主要酶防御机制，这表明在氯贝丁酯的毒性作用中，在过氧化物酶体水平上，涉及由活性氧介导的氧化应激机制。
