Muñiz P, Valls V, Perez-Broseta C, Iradi A, Climent J V, Oliva M R, Sáez G T
Department of Biochemistry and Molecular Biology, University of Valencia, Spain.
Free Radic Biol Med. 1995 Apr;18(4):747-55. doi: 10.1016/0891-5849(94)00200-4.
The effect of rifamycin SV on the formation of 8-hydroxy-2'-deoxyguanosine (8-0HdG) has been investigated in vitro and in vivo. Oxidative modification of 2'-deoxyguanosine has been measured as an indication of DNA damage using high-performance liquid chromatography with electrochemical detection. Rifamycin SV in the presence of copper(II) ions induces the formation of 8-0HdG in calf thymus DNA. The effect is enhanced by increasing the antibiotic concentration and inhibited by catalase and hydroxyl radical (.0H) scavengers, such as thiourea and ethanol, in a rifamycin SV concentration-dependent manner. The reduced glutathione (GSH) inhibits DNA damage, and this effect is proportional to the final concentration of the tripeptide in the incubation medium. A significant increase in the formation of 8-0HdG and of malondialdehyde (MDA) in rat liver DNA was observed only in GSH-depleted animals after 5 days of rifamycin SV treatment. These results support the involvement of hydrogen peroxide (H2(0)2) and .0H in the mechanism of the oxidative modification of DNA achieved by rifamycin SV. The role of other reactive species and the antioxidant properties of GSH against oxidative damage is also discussed.
已在体外和体内研究了利福霉素SV对8-羟基-2'-脱氧鸟苷（8-OHdG）形成的影响。使用高效液相色谱-电化学检测法测定2'-脱氧鸟苷的氧化修饰，以此作为DNA损伤的指标。在铜（II）离子存在的情况下，利福霉素SV会诱导小牛胸腺DNA中8-OHdG的形成。通过增加抗生素浓度可增强这种效应，而过氧化氢酶和羟基自由基（·OH）清除剂（如硫脲和乙醇）则以利福霉素SV浓度依赖性方式抑制这种效应。还原型谷胱甘肽（GSH）可抑制DNA损伤，且这种效应与孵育培养基中三肽的终浓度成正比。仅在经利福霉素SV处理5天的GSH耗竭动物的大鼠肝脏DNA中，观察到8-OHdG和丙二醛（MDA）形成显著增加。这些结果支持过氧化氢（H₂O₂）和·OH参与利福霉素SV导致的DNA氧化修饰机制。还讨论了其他活性物质的作用以及GSH对氧化损伤的抗氧化特性。
