Lipoic acid, treatment

At autopsy, multiple areas of necrosis are found in the grey matter of the central part of the brain and in the spinal cord [141]. Leigh compared these changes to Wernicke s encephalopathy, though with a different distribution. This suggested either thiamine deficiency or inability to utilize thiamine normally, but treatment with thiamine or thiamine pyrophosphate has no effect on the course of the disease [142]. Lipoic acid, like thiamine pyrophosphate involved in the oxidative decarboxylation of pyruvic acid, has been given to some patients [137] the concentration of pyruvic acid in the blood fell and clinical improvement was claimed. Others have tried lipoic acid treatment with less success—the pyruvic acid content of the blood fell, but there was no effect on the clinical course of the disease [136]. It is now known that the enzymes dec2irboxylating pyruvic acid are normal and that the metabolic error results from a lack of pyruvate carboxylase. 

As in the case of other cardiovascular diseases, the possibility of antioxidant treatment of diabetes mellitus has been studied in both animal models and diabetic patients. The treatment of streptozotocin-induced diabetic rats with a-lipoic acid reduced superoxide production by aorta and superoxide and peroxynitrite formation by arterioles providing circulation to the region of the sciatic nerve, suppressed lipid peroxidation in serum, and improved lens glutathione level [131]. In contrast, hydroxyethyl starch desferrioxamine had no effect on the markers of oxidative stress in diabetic rats. Lipoic acid also suppressed hyperglycemia and mitochondrial superoxide generation in hearts of glucose-treated rats [132],... 

Radiation is one of the most important known environmental stimuli of cancer development. This environmental factor becomes especially dangerous for humans living in the areas affected by irradiation from nuclear accidents. Earlier we found that the administration of a mixture of vitamin E and a-lipoic acid to children living in the area of Chernobyl nuclear accident significantly and synergistically suppressed leukocyte oxygen radical overproduction [211]. Thus a-lipoic acid and a-lipoic acid + vitamin E supplements may be of interest as antioxidant preventive agents for the treatment of radiation-induced cancer development. 

Treatment is largely symptomatic, and the prognosis ranges from dismal to guarded. Thiamine, lipoic acid, ketogenic diet and physostigmine have been tried in different concentrations and doses with equivocal results. Some patients with periodic ataxia resulting from PDHC deficiency may respond to acetazolamide. 

An interesting synthetic approach to thietanes is the selective desulfurization of cyclic disulfides.The treatment of dithiolanes with a diethyl-aminophosphine results in a ring contraction to thietanes, (Eq. 19). This has been demonstrated with a-lipoic acid, a coenzyme with a dithiolane structure involved in the biological oxidation of pyruvic acid. The reaction is proposed to be initiated by the electrophilic attack of the phosphorus on the ring sulfur atom, resulting in the formation of an acyclic internal phosphonium salt, which by subsequent elimination of a phosphine sulfide, closes to the four-membered ring. °... 

Biotin (68) is an essential growth factor for many microorganisms, but biotin deficiency is not normally found in man, except perhaps in infants. Its only therapeutic use is in the treatment of seborrhoeic dermatitis of infancy, but it has been tried for the treatment of some forms of baldness. Another heterocyclic sulfur compound, lipoic acid (69), serves as a prosthetic group in several enzymes but it has not been associated with any deficiency disease and has no therapeutic use. 

Holmquist L., Stuchbury G., Berbaum K., Muscat S., Young S., Hager K., Engel J., and Munch G. (2007). Lipoic acid as a novel treatment for Alzheimer s disease and related dementias. Pharmacol. Ther. 113 154-164. 

Numerous linkers have been developed with the aim of immobilizing substrates on a solid support. Commercially available (+)-a-lipoic acid has been employed as a novel, chemically stable linker for the immobilization of ketones. The utility of this thioacetal-based linker in solid-phase synthesis has been demonstrated by the synthesis of several 4-acetylbiphenyls by means of the Suzuki reaction. The products were readily cleaved from the solid support by treatment with [bis(trifluoroacetoxy)iodo]benzene [PhI(OCOCF3)2] [107]. 

The involvement of oxidative stress in AD has opened a new door for potential therapeutic targets. In this regard, several antioxidants are currently in clinical trials such as Idebenone, a-Lipoic acid, acetyl-L-carnitine (ALC), vitamin E, vitamin C, flavonoids, P-carotene, gingko biloba, and metal-chelating agents. Idebenone is a metabolic antioxidant and is normally synthesized as part of the mitochondrial oxidative phosphorylation system. Improvements in clinical status after treatment with idebenone have been shown in a dose-dependent manner compared to placebo and tacrine (Thai et al., 2003). 

Ester and amide derivatives of lipoic acid (i.e., 360 and 361) are capable of increasing the rate of glucose transport in myotubes in culture in the absence or presence of insulin <2004BMC1183>. Due to the improved lipid solubility, these compounds surpass the potency of LA, which is used as an auxiliary drug for the treatment of diabetes, by a few orders of magnitude. 

Alkyl lithium reagents, Grignard reagents, and cyanide ion attack 1,2-dithiolanes at a sulfur atom <84JCS(Pi)523, 88CL1339>. For example, lipoic acid (13) forms the acyclic product (96) on sequential treatment with methyl lithium and acetic anhydride. Dithiolanium salts are also attacked by alkenes, with ring expansion <82JA3231>. 

K. Hager A. Marahrens M. Kenklies P. Riederer G. Munch, Alpha-lipoic acid as a new treatment option for Alzheimer type dementia. Arch. Geron. Geri. 2001, 32, 275-282. 

Sulfur-containing compounds such as alpha-lipoic acid, methylsulfonylmethane, glutathione, N-acetylcysteine and cysteine are effective against oxidative stress and cell damage caused by free radicals (Bray and Taylor 1993, Pollack et al. 1996). Alpha-lipoic acid increases the antioxidant potency of further antioxidants such as vitamins E and C (Kagan et al. 1992). The course of acute pancreatitis is dramatically impaired in cases of very low antioxidant status. Whereas the sulfur antagonist selenium reduced remarkably the death rate (Kulinski et al. 1995), methionine was also used successfully in the treatment of this disease (Uden et al. 1990). 

Tankova T, Chemikova S, Koev D. Treatment for diabetic mononeuropathy with alfa-lipoic acid. Int J Clin Pract 2005 59(6) 645-650. 

PDH deficiency results in raised blood concentrations of pyruvate, lactate and alanine. Some patients respond to supplementation with lipoic acid or thiamin (coenzymes for PDH). Treatment with a low carbohydrate, ketogenic diet has been advocated but with limited success. (The ketone bodies readily cross the blood-brain barrier and their catabolism produces acetyl CoA independently of PDH.)... 

Combined treatment with D,L-a-lipoic acid and meso-2,3-dimercaptosuccinic acid reversed the decreases in the activities of renal y-glutamyl transferase (EC 2.3.2.2) and N-acetyl P-D-glucosaminidase (EC 3.2.1.17) evident in rats after the administration of lead citrate in drinking water for 5 weeks (Sivaprasad et al. 2002). 

One hour of pre-incubation with dihydrolipoic acid (1 iM), but not with a-hpoic acid (1 jiM), reduced damage of neurones from chick embryo telencephalon caused by 1 mM sodium cyanide or iron ions (Muller and Krieglstein 1995). a-Lipoic acid (1 (xM) reduced cyanide-induced neuronal damage when added 24 h before hypoxia, and pre-treatment with a-hpoic acid for >24h enhanced this neuroprotective effect. Both the R- and... 

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