title: The renal toxicity of (R)-3-chlorolactate in the rat.
abstract: 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.
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D004231:Diuresis / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects; D006029:Glycosuria / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects*; D007773:Lactates / Q000633:toxicity*; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D051381:Rats
chemical_list: D007773:Lactates; C007000:3-chlorolactate; D000105:Acetyl Coenzyme A; D008291:Malate Dehydrogenase