Rauhala P, Khaldi A, Mohanakumar K P, Chiueh C C
Unit on Neurodegeneration and Neuroprotection, National Institute of Mental Health, Bethesda, MD 20892-1264, USA.
Free Radic Biol Med. 1998 May;24(7-8):1065-73. doi: 10.1016/s0891-5849(97)00386-9.
Sodium nitroprusside (disodium nitroferricyanide) has been suggested to cause cytotoxicity through either the release of cyanide and/or nitric oxide. The present study investigated a possible mechanism that after a brief release of nitric oxide, iron moiety of breakdown products of sodium nitroprusside could cause a long lasting oxidative stress, such as hydroxyl radical generation, lipid peroxidation and cytotoxicity. Intranigral administration of sodium nitroprusside (0-16.8 nmol) to rats induced an acute increase in lipid peroxidation in the substantia nigra and a chronic dopamine depletion in the caudate nucleus. Photodegraded (nitric oxide-exhausted) sodium nitroprusside, however, still produced lipid peroxidation and neurotoxicity in the midbrain. Moreover, non-iron containing nitric oxide-donor compounds, such as S-nitroso-N-acetylpenicillamine, did not cause oxidative brain injury in vivo suggesting that nitric oxide may not mediate neurotoxicity induced by sodium nitroprusside. Additional in vitro studies demonstrated that both freshly prepared (nitric oxide donor) and photodegraded (nitric oxide-exhausted) sodium nitroprusside generated hydroxyl radicals in the presence of ascorbate and also increased lipid peroxidation in brain homogenates. These pro-oxidative effects of sodium nitroprusside were blocked by nitric oxide, S-nitroso-N-acetylpenicillamine, oxyhemoglobin, and deferoxamine (iron chelator). The present results suggest that iron moiety, rather than nitric oxide, may mediate the pro-oxidative properties of sodium nitroprusside. With this new information in mind, the misuse of sodium nitroprusside as a selective nitric oxide donor in both basic and clinical uses should be urgently addressed.
有人提出硝普钠（二氰合铁（II）酸钠）通过释放氰化物和/或一氧化氮导致细胞毒性。本研究调查了一种可能的机制，即在一氧化氮短暂释放后，硝普钠分解产物的铁部分可能导致持久的氧化应激，如羟基自由基生成、脂质过氧化和细胞毒性。向大鼠黑质内注射硝普钠（0 - 16.8纳摩尔）可导致黑质脂质过氧化急性增加以及尾状核慢性多巴胺耗竭。然而，光降解（一氧化氮耗尽）的硝普钠仍能在中脑产生脂质过氧化和神经毒性。此外，不含铁的一氧化氮供体化合物，如S - 亚硝基 - N - 乙酰青霉胺，在体内不会引起氧化性脑损伤，这表明一氧化氮可能不会介导硝普钠诱导的神经毒性。额外的体外研究表明，新鲜制备的（一氧化氮供体）和光降解的（一氧化氮耗尽）硝普钠在抗坏血酸存在下均能产生羟基自由基，并且还会增加脑匀浆中的脂质过氧化。硝普钠的这些促氧化作用被一氧化氮、S - 亚硝基 - N - 乙酰青霉胺、氧合血红蛋白和去铁胺（铁螯合剂）所阻断。目前的结果表明，介导硝普钠促氧化特性的可能是铁部分，而非一氧化氮。鉴于这一新信息，应紧急解决在基础和临床应用中滥用硝普钠作为选择性一氧化氮供体的问题。
