Giuffrida S, De Guidi G, Miano P, Sortino S, Condorelli G, Costanzo L L
Dipartimento di Scienze Chimiche, Università di Catania, Italy.
J Inorg Biochem. 1996 Sep;63(4):253-63. doi: 10.1016/0162-0134(95)00226-x.
The inhibitory effect of Cu2+, Mn2+, Co2+, and I- on naproxen-induced photohemolysis was investigated. In order to better understand this effect, these ions were also tested for lipid peroxidation and protein crosslinking, which are among the main processes involved in erythrocyte membrane damage. The overall results support the hypothesis that metal cations act via a redox scavenging of the radicals which are produced on the lipid component of the membrane. This process occurs through hydrogen abstraction operated by photogenerated naproxen radicals. Moreover, copper can also act as a superoxide anion scavenger: its decay is noxious in photohemolysis, whereas it is not in lipid peroxidation. Metal cations, besides, are not able to scavenge protein crosslinking. On the other hand, iodide is able to reduce both processes because it acts as a heavy atom, favoring intersystem crossing to the unreactive triplet state of the drug, thus reducing naproxen photolysis and, as a consequence, the amount of the damaging species produced. This mechanism was supported by luminescence experiments performed in the absence and in the presence of iodide.
研究了Cu2+、Mn2+、Co2+和I-对萘普生诱导的光溶血的抑制作用。为了更好地理解这种作用，还对这些离子进行了脂质过氧化和蛋白质交联测试，这是红细胞膜损伤的主要过程。总体结果支持这样的假设，即金属阳离子通过对膜脂质成分上产生的自由基进行氧化还原清除来发挥作用。这个过程是通过光生萘普生自由基进行的氢提取而发生的。此外，铜还可以作为超氧阴离子清除剂：其衰变在光溶血中是有害的，而在脂质过氧化中则不是。此外，金属阳离子无法清除蛋白质交联。另一方面，碘化物能够减少这两个过程，因为它作为重原子，有利于系间窜越到药物的非反应性三重态，从而减少萘普生的光解，进而减少产生的损伤性物质的量。在不存在和存在碘化物的情况下进行的发光实验支持了这一机制。
