Kilic F, Handelman G J, Serbinova E, Packer L, Trevithick J R
Dept. of Biochemistry, University of Western Ontario, London, Canada.
Biochem Mol Biol Int. 1995 Oct;37(2):361-70.
The effect of R, S, and racemic forms of a-lipoic acid was tested on the formation of opacity in normal rat lenses incubated with 55.6 mM glucose, as a model for in vivo diabetic cataractogenesis. Control lenses, incubated 8 days with 5.56 mM glucose, did not develop opacities. Formation of lens opacities in vitro was correlated with lactate dehydrogenase (LDH) leakage into the incubation medium. Opacity formation and LDH leakage, resulting from incubation in medium containing 55.6 mM glucose to model diabetes, were both suppressed by the addition of 1 mM R-lipoic acid. Addition of 1 mM racemic lipoic acid reduces these damaging effects to the lens by one-half, while S-lipoic acid potentiated LDH leakage, consistent with the hypothesis that R-lipoic acid is the active form. Although HPLC analysis demonstrated that both stereoisomers of lipoic acid were reduced to dihydrolipoate at comparable rates by the intact lens, the mitochondrial lipoamide dehydrogenase system is highly specific for reduction of exogenous R-lipoic to dihydrolipoic acid. Therefore, stereospecific protection against this opacity is consistent with specific reduction of R-lipoic acid in mitochondria of the vulnerable cells at the lens equator where the first globular degeneration is seen in glucose cataract.
以55.6 mM葡萄糖孵育正常大鼠晶状体形成混浊作为体内糖尿病性白内障发生的模型，测试了R型、S型和消旋型α-硫辛酸的作用。用5.56 mM葡萄糖孵育8天的对照晶状体未出现混浊。体外晶状体混浊的形成与乳酸脱氢酶（LDH）泄漏到孵育培养基中有关。在含55.6 mM葡萄糖的培养基中孵育以模拟糖尿病，由此导致的混浊形成和LDH泄漏均被添加1 mM R-硫辛酸所抑制。添加1 mM消旋硫辛酸可将这些对晶状体的损伤作用降低一半，而S-硫辛酸则增强了LDH泄漏，这与R-硫辛酸是活性形式的假设一致。尽管高效液相色谱分析表明，硫辛酸的两种立体异构体在完整晶状体中以相当的速率被还原为二氢硫辛酸，但线粒体硫辛酰胺脱氢酶系统对外源性R-硫辛酸还原为二氢硫辛酸具有高度特异性。因此，对这种混浊的立体特异性保护与在晶状体赤道部易损细胞的线粒体中R-硫辛酸的特异性还原一致，在葡萄糖性白内障中首先出现球状变性的部位就在晶状体赤道部。
