Kostyuk V A, Potapovich A I, Speransky S D, Maslova G T
Laboratory of Bioenergetics, Byelorussian State University, Minsk, Belarus.
Free Radic Biol Med. 1996;21(4):487-93. doi: 10.1016/0891-5849(96)00117-7.
Exposure of macrophages to asbestos fibers resulted in enhancement of the production of oxygen radicals, determined by a lucigenin enhanced chemiluminescence (LEC) assay, a formation of thiobarbituric acid reactive substances (TBARS), a LDH release into the incubation mixture, and a rapid lysis of the cells. Rutin (Rut) and quercetin (Qr) were effective in inhibiting LEC, TBARS formation, and reducing peritoneal macrophages injury caused by asbestos. The concentrations pre-treatment of antioxidants that were required to prevent the injury of peritoneal macrophages caused by asbestos by 50% (IC50) were 90 microM and 290 microM for Qr and Rut, respectively. Both flavonoids were found to be oxidized during exposure of peritoneal macrophages to asbestos and the oxidation was SOD sensitive. The efficacy of flavonoids as antioxidant agents as well as superoxide ion scavengers was also evaluated using appropriate model systems, and both quercetin and rutin were found to be effective in scavenging O2.-. These findings indicate that flavonoids are able to prevent the respiratory burst in rat peritoneal macrophages exposed to asbestos at the stage of activated oxygen species generation, mainly as superoxide scavengers. On the basis of this study it was concluded that natural flavonoids quercetin and rutin would be promising drug candidates for a prophylactic asbestos-induced disease.
巨噬细胞暴露于石棉纤维会导致氧自由基生成增加，这通过光泽精增强化学发光（LEC）测定、硫代巴比妥酸反应性物质（TBARS）的形成、乳酸脱氢酶（LDH）释放到孵育混合物中以及细胞的快速裂解来确定。芦丁（Rut）和槲皮素（Qr）可有效抑制LEC、TBARS的形成，并减轻石棉引起的腹膜巨噬细胞损伤。预防石棉引起的腹膜巨噬细胞损伤50%（IC50）所需的抗氧化剂预处理浓度，槲皮素为90微摩尔，芦丁为290微摩尔。发现两种黄酮类化合物在腹膜巨噬细胞暴露于石棉期间均被氧化，且这种氧化对超氧化物歧化酶（SOD）敏感。还使用适当的模型系统评估了黄酮类化合物作为抗氧化剂以及超氧阴离子清除剂的功效，发现槲皮素和芦丁均能有效清除超氧阴离子（O2.-）。这些发现表明，黄酮类化合物能够在活性氧生成阶段防止暴露于石棉的大鼠腹膜巨噬细胞发生呼吸爆发，主要作为超氧化物清除剂。基于这项研究得出结论，天然黄酮类化合物槲皮素和芦丁有望成为预防石棉诱导疾病的候选药物。
