Porter K E, Jones A R
Chem Biol Interact. 1987;62(2):157-66. doi: 10.1016/0009-2797(87)90087-1.
The renal toxicity of (R,S)-3-chlorolactate has been shown to be due to the (R)-isomer which, when administered to rats, induces diuresis and glucosuria. The metabolic activity of isolated tubule cells, prepared from rat kidney, was inhibited by (R)-3-chlorolactate and the action of the compound was localised as affecting mitochondrial metabolism. Studies with kidney mitochondria pin-pointed the site of action as being involved with the oxidative metabolism of malate but not the inhibition of mitochondrial malate dehydrogenase. The effects of oxalate, a metabolite of (R)-3-chlorolactate, and of (R,S)-3-chlorolactaldehyde on renal tubule cells was investigated. While some degrees of inhibition of metabolic activity were evident, these compounds were not responsible for the toxic effects produced by (R)-3-chlorolactate.
已表明（R,S）-3-氯乳酸的肾毒性归因于（R）-异构体，该异构体给大鼠给药时会诱导利尿和糖尿。从大鼠肾脏制备的分离肾小管细胞的代谢活性受到（R）-3-氯乳酸的抑制，且该化合物的作用定位于影响线粒体代谢。对肾线粒体的研究确定作用位点与苹果酸的氧化代谢有关，但与线粒体苹果酸脱氢酶的抑制无关。研究了（R）-3-氯乳酸的代谢产物草酸盐以及（R,S）-3-氯乙醛对肾小管细胞的影响。虽然代谢活性有一定程度的抑制，但这些化合物并非（R）-3-氯乳酸产生毒性作用的原因。
