Valeri F, Boess F, Wolf A, Göldlin C, Boelsterli U A
Institute of Toxicology, ETH, Schwerzenbach, Switzerland.
Free Radic Biol Med. 1997;22(1-2):257-68. doi: 10.1016/s0891-5849(96)00331-0.
To further investigate the mechanism by which fructose affords protection against oxidative cell injury, cultured rat hepatocytes were exposed to cocaine (300 microM) or nitrofurantoin (400 microM). Both drugs elicited massively increased lactate dehydrogenase release. The addition of the ketohexoses D-fructose (metabolized via glycolysis) or D-tagatose (poor glycolytic substrate) significantly attenuated cocaine- and nitrofurantoin-induced cell injury, although both fructose and tagatose caused a rapid depletion of ATP and compromised the cellular energy charge. Furthermore, fructose, tagatose, and sorbose all inhibited in a concentration-dependent manner (0-16 mM) luminolenhanced chemiluminescence (CL) in cell homogenates, indicating that these compounds inhibit the iron-dependent reactive oxygen species (ROS)-mediated peroxidation of luminol. Indeed, both Fe2+ and Fe3+ further increased cocaine-stimulated CL, which was markedly quenched following addition of the ketohexoses. The iron-independent formation of superoxide anion radicals (acetylated cytochrome c reduction) induced by the prooxidant drugs remained unaffected by fructose or tagatose. The iron-chelator deferoxamine similarly protected against prooxidant-induced cell injury. In contrast, the nonchelating aldohexoses D-glucose and D-galactose did not inhibit luminol CL nor did they protect against oxidative cell injury. These data indicate that ketohexoses can effectively protect against prooxidant-induced cell injury, independent of their glycolytic metabolism, by suppressing the iron-catalyzed formation of ROS.
为了进一步研究果糖对细胞氧化损伤提供保护作用的机制，将培养的大鼠肝细胞暴露于可卡因（300微摩尔）或呋喃妥因（400微摩尔）中。两种药物均引起乳酸脱氢酶释放大量增加。添加己酮糖D-果糖（通过糖酵解代谢）或D-塔格糖（不良糖酵解底物）可显著减轻可卡因和呋喃妥因诱导的细胞损伤，尽管果糖和塔格糖都会导致ATP迅速消耗并损害细胞能量状态。此外，果糖、塔格糖和山梨糖均以浓度依赖性方式（0-16毫摩尔）抑制细胞匀浆中鲁米诺增强的化学发光（CL），表明这些化合物抑制铁依赖性活性氧（ROS）介导的鲁米诺过氧化反应。事实上，Fe2+和Fe3+都会进一步增加可卡因刺激的CL，添加己酮糖后CL明显减弱。由促氧化剂药物诱导的超氧阴离子自由基的非铁依赖性形成（乙酰化细胞色素c还原）不受果糖或塔格糖的影响。铁螯合剂去铁胺同样能保护细胞免受促氧化剂诱导的损伤。相比之下，非螯合的醛糖D-葡萄糖和D-半乳糖既不抑制鲁米诺CL，也不能保护细胞免受氧化损伤。这些数据表明，己酮糖可以通过抑制铁催化的ROS形成，有效地保护细胞免受促氧化剂诱导的损伤，而与它们的糖酵解代谢无关。
