Reversal of Selective Toxicity of (-)-α-Lipoic Acid by Thiamine in Thiamine-deficient Rats
Abstract
INTRAPERITONEAL injection of (+/-)-α-lipoic acid has been reported to be toxic to thiamine-deficient rats1. Development of the toxic effect was prevented by simultaneous injection of 100 µg of thiamine hydrochloride. It was also noticed that (+/-)-α-lipoic acid, unlike neopyrithiamine, had no effect on thiamine excretion. The toxicity of (+/-)-α-lipoic acid to thiamine-deficient rats therefore could not be related to the depletion of the thiamine reserves present in the organs of thiamine-deficient animals. Obviously, the results obtained from the use of the racemic form of lipoic acid could not reveal whether both or one of the isomers had been responsible for the toxic effects in the deficient animals. In order to clarify the relative toxicity of the isomers of lipoic acid in thiamine-deficient rats, the experiments were repeated with the natural and unnatural isomers of α-lipoic acid. The preparation of pure (+)-α-lipoic acid was accomplished from (+)-6,8-dichlorooctanoic acid (-)-ephedrine salt2. However, the (-)-α-lipoic acid was found to be contaminated with 15-20 per cent of the dextro-rotatory enantiomorph2. Therefore, the pure (-)-α-lipoic acid was synthesized from the purified (-)-6,8-dichlorooctanoic acid (+)-ephedrine salt. This was obtained after converting a sample of (-)-6,8-dichlorooctanoic acid (-)-ephedrine salt into the (+)-ephedrine salt. (The (-)-6,8-dichlorooctanoic acid (-)-ephedrine salt was generously supplied by Dr. W. J. Wayne of Du Pont.)
- Publication:
-
Nature
- Pub Date:
- July 1965
- DOI:
- 10.1038/207535a0
- Bibcode:
- 1965Natur.207..535G