Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Thioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial

Abstract

Peripheral neuropathies, characterized by altered nociceptive and muscular functions, are related to oxidative stress. Thioctic acid is a natural antioxidant existing as two optical isomers, but most clinically used as racemic mixture. The present study investigated the central nervous system’s changes which followed loose-ligation-derived compression of sciatic nerve, the putative neuroprotective role of thioctic acid and the pain-alleviating effect on low-back pain suffering patients. Loose ligation of the right sciatic nerve was performed in spontaneously hypertensive rats (SHR), a model of increased oxidative stress, and in normotensive Wistar-Kyoto rats (WKY). Animals with sciatic nerve ligation were left untreated or were treated intraperitoneally for 15 days with 250 μmol·kg−1·die−1 of (+/−)-thioctic acid; 125 μmol·kg−1·die−1 of (+/−)-thioctic acid; 125 μmol·kg−1·die−1 of (+)-thioctic acid lysine salt; 125 μmol·kg−1·die−1 of (−)-thioctic acid; 300 μmol·kg−1·die−1 pregabalin. Control SHR and WKY rats received the same amounts of vehicle. The clinical trial NESTIORADE (Sensory-Motor Neuropathies of the Sciatic Nerve: Comparative evaluation of the effect of racemic and dextro-rotatory forms of thioctic acid) examined 100 patients (49 males and 51 females aged 53 ± 11 years) dividing them into two equal-numbered groups, each treated daily for 60 days with 600 mg of (+/−)-thioctic acid or (+)-thioctic acid, respectively. The trial was registered prior to patient enrollment at EudraCT website (OSSC Number: 2011-000964-81). In the preclinical study, (+)-thioctic acid was more active than (+/−)- or (−)-enantiomers in relieving pain and protecting peripheral nerve as well as in reducing oxidative stress and astrogliosis in the spinal cord. Main findings of NESTIORADE clinical trial showed a greater influence on painful symptomatology, a quicker recovery and a better impact on quality of life of (+)-thioctic acid vs. (+/−)-thioctic acid. These data may have a pharmacological and pharmacoeconomical relevance and suggest that thioctic acid, above all (+)-enantiomer, could be considered for treatment of low-back pain involving neuropathy.

Antioxidant Properties of Alpha-Lipoic (Thioctic) Acid Treatment on Renal and Heart Parenchyma in a Rat Model of Hypertension

“…Compounds were solubilized in NaOHsupplemented physiologic solution and buffered to 7.4 pH by adding HCl. Different racemic and lipoic acid salt compounds were solubilized in saline [25] and SHR rats were treated once a day for 30 days with an i.p. injection of 250 µmol/kg/day of (+/-)-ALA (n = 6); 125 µmol/kg/day of (+/-)-ALA (n = 6); 125 µmol/kg/day of (+)-ALA (n = 6) and 125 µmol/kg/day of (-)-ALA (n = 6).…”

“…4354-MC-050) diluted 1:250. This mouse monoclonal antibody specifically binds to 8-oxo-dG within DNA, as detailed [25]. The product of the immune reaction was then revealed by exposing slides with anti-mouse biotinylated polyclonal antibody (Merck-Millipore, Burlington, MA, USA, Cat.…”

“…In SHR, we already assessed the neuroprotective activity of ALA in central nervous system lesions consequent to peripheral nerve injury [24]. Recently, data from the spinal cord could explain the protection of ALA on the brain [25]. Finally, the use of ALA for therapeutic purposes was reviewed by [26].…”

Efficacy of the R(+)-enantiomer of alpha-lipoic acid in clinical practice

“…Огляд літератури /Literature Review/ попереку [3]. До дослідження було залучено 100 пацієнтів з радикулопатією нижніх кінцівок (однобічною або двобічною), яких було розподілено на дві групи по 50 осіб у кожній.…”

R- Is Superior to S-Form of α-Lipoic Acid in Anti-Inflammatory and Antioxidant Effects in Laying Hens

“…In a dose/response curve model of R-LA and S-LA in the working rat heart during reoxygenation, the R-enantiomer was found to be more superior in the enhancement of the aortic flow [ 19 ]. Moreover, in a model of sciatic nerve injury in hypertensive rats, R-LA was more active than S-LA in terms of analgesic and neuroprotective efficacy [ 20 , 21 ]. This may be related to the better recognized dextrorotatory enantiomer by enzymes, as it was found that the maximum plasma concentration (Cmax) is approximately 40–50% higher with R-LA than with S-LA at the same dose [ 11 ].…”