Alpha-lipoic Acid Supplementation Research Articles

Influence of alpha lipoic acid on antioxidant status in D-galactosamine-induced hepatic injury

D-Galactosamine (GalN)-induced liver injury is associated with reactive oxygen species and oxidative stress. In the present study, we evaluated the effect of alpha lipoic acid (ALA) supplementation on acute GalN-induced oxidative liver injury. Hepatotoxicity induced by single intraperitoneal injection of GalN (500 mg/kg body wt) was evident from increase in lipid peroxidation and serum marker enzymes (asparate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase). The decreased activities of enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) as well as glutathione levels were the salient features observed in GalN-induced hepatotoxicity. Pretreatment with ALA (50 mg/kg body weight for 7 days) significantly precluded these changes and prevents the hepatic injury. Hence, this study clearly exemplified that ALA might be a suitable candidate against GalN-induced cellular abnormalities.

Retracted: Alpha-lipoic acid supplementation and diabetes

Diabetes is a common metabolic disorder that is usually accompanied by increased production of reactive oxygen species or by impaired antioxidant defenses. Importantly, oxidative stress is particularly relevant to the risk of cardiovascular disease. Alpha-lipoic acid (LA), a naturally occurring dithiol compound, has long been known as an essential cofactor for mitochondrial bioenergetic enzymes. LA is a very important micronutrient with diverse pharmacologic and antioxidant properties. Pharmacologically, LA improves glycemic control and polyneuropathies associated with diabetes mellitus; it also effectively mitigates toxicities associated with heavy metal poisoning. As an antioxidant, LA directly terminates free radicals, chelates transition metal ions, increases cytosolic glutathione and vitamin C levels, and prevents toxicities associated with their loss. These diverse actions suggest that LA acts by multiple mechanisms both physiologically and pharmacologically. Its biosynthesis decreases as people age and is reduced in people with compromised health, thus suggesting a possible therapeutic role for LA in such cases. Reviewed here is the known efficacy of LA with particular reference to types 1 and 2 diabetes. Particular attention is paid to the potential benefits of LA with respect to glycemic control, improved insulin sensitivity, oxidative stress, and neuropathy in diabetic patients. It appears that the major benefit of LA supplementation is in patients with diabetic neuropathy.

The Beneficial Effect of Coenzyme Q10 and Lipoic Acid on Obstructive Bladder Dysfunction in the Rabbit

Recent evidence indicates that ischemia and reperfusion are major etiological factors in the bladder dysfunction that occurs after partial bladder outlet obstruction. Coenzyme Q10 and alpha-lipoic acid are found naturally in mitochondria and act as potent antioxidants. We investigated the beneficial effects of coenzyme Q10 plus alpha-lipoic acid in a rabbit model of bladder outlet obstruction. Twenty male rabbits were divided into 5 groups. Group 1 served as control and group 2 received three weeks of coenzyme Q10 plus alpha-lipoic acid supplementation. Rabbits in group 3 underwent surgical partial bladder outlet obstruction for duration of four weeks and groups 4 and 5 were obstructed for seven weeks. In group 5, coenzyme Q10 plus alpha-lipoic acid supplementation was given following 4 weeks obstruction and continued till the end of the seven weeks. The contractile responses to various agents were determined. The protein nitration and carbonylation levels were studied by immunoblotting. Nerve function was determined by choline acetyltransferase activity and nerve density. The contractile responses to different forms of stimulations, including field stimulation, ATP, carbachol and KCl all showed decreases following 4 and 7 weeks obstruction. Treatment with coenzyme Q10 plus alpha-lipoic acid significantly restored contractile responses to all forms of stimulation. Treatment also had mitochondrial and neuronal effects and reduced protein nitration and carbonylation. Histologically there was less detrusor muscle hypertrophy. The current study clearly demonstrates that coenzyme Q10 and alpha-lipoic acid supplementation can improve bladder function after outlet obstruction.

Coenzyme Q(10) and alpha-lipoic acid supplementation in diabetic rats: Conduction velocity distributions

Diabetic neuropathies are a family of nerve disorders caused by diabetes. Patients with diabetes can develop nerve problems at any time, but the longer a person has diabetes the greater the risk. This study aims to investigate diabetes- and coenzyme Q(10) (CoQ(10)) or alpha-lipoic acid (ALA) supplementation-induced changes in the conduction velocity (CV) distributions of rat sciatic nerve fibers. Sciatic nerve compound action potentials (CAPs) were recorded by suction electrode and CV distributions by the collision technique. Diabetes resulted in a significant increase in time to peak, rheobase and chronaxie values of these CAP waveforms, whereas the maximum depolarization, area, kinetics and CVs of both fast and slow nerve fiber groups were found to be decreased. Coenzyme Q(10) (CoQ(10)) supplementation was found to have some positive effect on the diabetes-induced alterations. CoQ(10) supplementation induced positive changes mainly in the area and fall-down phase of the kinetics of CAP waveforms, as well as rheobase, chronaxie and speed of the intermediately conducting groups ( approximately or equal to 40 m/s). alpha-Lipoic acid (ALA) supplementation did not produce statistically significant effects. This study has shown for the first time that diabetes induces a shift of actively contributing nerve fibers toward slower CVs, and supplementation with CoQ(10) not only stopped this shift but also tended to restore velocities toward those of the age-matched control group. In addition to its effects on mitochondrial alterations, these positive effects of CoQ10 on diabetic neuropathy can be attributed to its antioxidant activity.

Coenzyme Q10 and alpha-lipoic acid supplementation in diabetic rats: Conduction velocity distributions

Coenzyme Q10 and alpha-lipoic acid supplementation in diabetic rats: Conduction velocity distributions

규칙적인 운동과 Alpha-Lipoic Acid 섭취가 중년 비만여성의 혈중 콜레스테롤 및 C-reactive Protein과 Homocystein의 변화에 미치는 영향

규칙적인 운동과 Alpha-Lipoic Acid 섭취가 중년 비만여성의 혈중 콜레스테롤 및 C-reactive Protein과 Homocystein의 변화에 미치는 영향

Effects of Alpha-Lipoic Acid Supplementation in Peripheral Arterial Disease: A Pilot Study

To examine whether 3 months of lipoic acid (LA) supplementation improved walking tolerance and delayed claudication pain onset in peripheral arterial disease (PAD). Randomized, double-blind, controlled study. General Clinical Research Center. Twenty-eight (28) participants (15 men, 13 women) with PAD (ankle brachial index range 0.9-0.4, mean age 73.2 +/- 1.6 years). LA (600 mg/day) or placebo for 3 months. Walking tolerance was assessed by 6-minute walk test distance, 4-meter walk time, initial claudication pain time (ICT) and distance (ICD), and peak claudication pain. Serum was assessed for inflammation (C-reactive protein [CRP]) and oxidative stress (lipid hydroperoxides) as potential mechanisms for changes in walking tolerance. ICT increased 34.4% and 15%, ICD was reduced by 40.5% and 18%, and peak claudication pain ratings were reduced by 93% and 7% in LA and placebo groups, respectively. Although the improvements in peak pain and ICT achieved significance within the LA group (both p<0.05), the interactions of group by time were not found to be significant (p>0.05). Oxidative stress and CRP measures were not different between groups by month 3 (p>0.05). There were no serious side-effects associated with the LA. LA may confer pain relief during exercise. However, longer and larger trials are warranted to determine long-term effects of LA alone or combined with other interventions on PAD symptoms.

Effect of Alpha-lipoic Acid Supplementation on Trace Element Levels in Serum and in Postmitotic Tissue in Aged Rats

Redistribution of redox-active divalent metal ions (e.g. copper, zinc, and iron) in postmitotic tissues of lipoic acid supplemented aging rats has been proposed to contribute to metal-catalyzed protein oxidation. DL-alpha lipoic acid (LA) (100 mg/kg body wt/day) was administered intraperitoneally to the Sprague-Dawley rats for 14 days. Serum copper levels lowered in the aged rats with LA supplementation compared to the rats without LA supplementation. On the other hand, serum zinc and iron levels increased in the aged rats with LA supplementation compared to the rats without LA supplementation. Copper levels of the postmitotic tissues were not changed in the aged rats with LA supplementation compared to the controls. The heart zinc levels detected in LA supplemented rats were significantly lower than controls. Similarly, the iron levels of the heart were found to be significantly lower in LA supplemented rats when compared to control rats. LA supplementation did not affect brain and muscle iron levels. The brain and muscle zinc levels remained the same in both group of rats. Based on the findings of our study, we have concluded that LA may exhibit prooxidant effect depending on the altered trace element homeostasis. Therefore, our results emphasize the importance of monitoring the dose of LA supplementation, duration of treatment and its potential harmful effects in the postmitotic tissues of aged rats.

Alpha-Lipoic Acid Modulates Heat Shock Factor-1 Expression in Streptozotocin-Induced Diabetic Rat Kidney

Increased oxidative stress and impaired heat shock protein (HSP) synthesis may contribute to diabetic nephropathy. The question of whether 8-week thiol antioxidant alpha-lipoic acid (LA) supplementation modulates HSP response and oxidative stress was studied in the kidney of streptozotocin-induced diabetic (SID) and nondiabetic rats. SID caused a histological mesangial expansion, tubular dilatation, and increased levels of transforming growth factor-beta (TGF-beta), a mediator of glomerulosclerosis. SID increased 4-hydroxynonenal (4-HNE) protein adduct formation, a marker of lipid peroxidation, and heme oxygenase-1 (HO-1), also a marker of oxidative stress. Moreover, SID increased the DNA-binding activity of heat shock factor-1 (HSF-1) and expression of heat shock protein 60 (HSP60). In contrast, LA supplementation partially reversed histological findings of glomerulosclerosis and decreased TGF-beta. LA also increased HSF-1 and decreased HO-1 protein expression, without affecting 4-HNE protein adduct levels. At the mRNA level, LA increased expression of HSF-1, HSP90, and glucose-regulated protein (GRP75) in both control and diabetic animals and HSP72 in SID rats. However, LA supplementation did not affect these HSPs at the protein level. These findings suggest that in addition to its antiglomerulosclerotic effects, LA can induce cytoprotective response in SID.

Efficacy and Safety of α-Lipoic Acid Supplementation in the Treatment of Symptomatic Diabetic Neuropathy

The purpose of this article is to review current evidence available for alpha-lipoic acid (ALA) and its ability to improve symptoms of peripheral diabetic neuropathy (PDN). This article searched MEDLINE from 1966 to November 2005 to identify clinical trials that supplemented ALA to individuals with type 1 or type 2 diabetes and positive sensory symptoms of PDN. Clinical trials to be included in this review met specific criteria of randomization, double masking, and placebo-controlled design. The search results produced 5 clinical trials that met the prerequisites for this review. ALA appears to improve neuropathic symptoms and deficits when administered via parenteral supplementation over a 3-week period. Oral treatment with ALA appears to have more conflicting data whether it improves sensory symptoms or just neuropathic deficits alone. An oral regimen of ALA and optimal length of treatment remains unclear. Both parenteral and up to a 2-year time period of oral supplementation of ALA appears to be safe without affecting glycemic control. Based on these results, ALA should be considered as a treatment option for patients with PDN. When discussing supplementation with patients, it is important to discuss potential side effects; vitamin, mineral, and drug interactions; and current evidence available regarding efficacy.

α-Lipoic acid attenuates x-irradiation-induced oxidative stress in mice

The development of nontoxic but effective radioprotectors is needed because of the increasing risk of human exposure to ionizing radiation. We have reported that alpha-lipoic acid confers considerable radio-protective effect in mouse tissues when given prior to x-irradiation. In the present study, alpha-lipoic acid supplementation prior to x-irradiation with 4 and 6 Gy significantly inhibited the radiation-induced decline in total antioxidant capacity (TAC) of plasma. Radiation-induced decline in non-protein sulfhydryl content (NPSH) of different tissues, namely, brain, liver, spleen, kidney, and testis, was also ameliorated significantly at both 4 and 6 Gy doses. Maximal augmentation of radiation-induced protein carbonyl content was observed in spleen followed by brain, kidney, testis, and liver. Maximal protection in terms of carbonyl content was observed in spleen (116%) at 6 Gy dose, and minimal protection was found in liver (22.94%) at 4 Gy dose. Maximal increase in MDA (malondialdehyde) content was observed in brain, followed by testis, spleen, kidney, and liver. Protection by alpha-lipoic acid pretreatment in terms of MDA content was maximal in brain (51.67%) and minimal in spleen. The findings support the idea that alpha-lipoic acid is a free-radical scavenger and a potent antioxidant.

Effect of dietary α-lipoic acid on growth, body composition, muscle pH, and AMP-activated protein kinase phosphorylation in mice1

The effects of alpha-lipoic acid (ALA) on the growth, body composition, postmortem AMP-activated protein kinase (AMPK) activation, and 24-h muscle pH were investigated. Thirty male C57BL/6J mice were fed diets containing 0, 0.5, or 1.0% ALA (DM basis). At the end of the 3-wk feeding trial, carcass weights decreased (P < 0.05) 14 and 30% for mice fed 0.5 and 1.0% ALA, respectively, compared with the 0% group, with decreases in BW as the levels of dietary ALA increased. This change in carcass weight occurred because carcass fat content for mice receiving 0.5 and 1.0% ALA was 7.32 and 8.09% lower (P < 0.05), respectively, than for the 0% ALA treatment, and because gonadal fat decreased (P < 0.05) 85% in mice fed 1.0% ALA compared with those fed 0% ALA. Dietary ALA caused a slight increase (P < 0.05) in carcass moisture content, with no (P = 0.07) effect on protein and ash content. Furthermore, ALA supplement decreased (P < 0.05) ADFI (DM basis) from 4.3 g/d for 0% ALA-fed mice to 3.4 g/d for 1.0% ALA-fed mice. At 20 min postmortem, pH was greater (P < 0.05) in muscle of mice fed 1.0% ALA than in muscle of mice fed 0% ALA. Ultimate (24-h) pH values differed (P < 0.05) among treatments, and mean values were 5.83, 6.08, and 6.29 for 0, 0.5, and 1.0% ALA, respectively. Phosphorylation of AMPK alpha subunit at Thr172, an indicator of AMPK activation, was decreased (P < 0.05) in muscle of ALA-treated mice at 20 min postmortem. Because AMPK has a crucial role in the control of glycolysis, the reduction in AMPK activation decreases glycolysis, and thereby increases the ultimate pH of postmortem muscle. In summary, dietary ALA supplement can decrease fat accumulation in mice, and because ALA increased muscle pH at 20 min and 24 h postmortem, these results suggest that dietary ALA supplementation might decrease carcass fatness and prevent the development of PSE pork and poultry. However, further research is required to test the effects of ALA in swine and poultry.

Effect of alpha-lipoic acid supplementation on markers of protein oxidation in post-mitotic tissues of ageing rat

In the present study, we investigated whether DL-alpha-lipoic acid (LA) supplementation could have prooxidant or antioxidant effects on oxidative protein damage parameters such as protein carbonyl (PCO), nitrotyrosine (NT), advanced oxidation protein products (AOPP), and protein thiol (P-SH), as well as oxidative stress parameters such as total thiol (T-SH), non-protein thiol (Np-SH), and lipid hydroperoxide (LHP) in the brain and the skeletal muscle tissue of aged rats. PCO, and NT levels were increased, AOPP and P-SH levels were not changed in the brain tissue of aged rats given LA supplementation. On the other hand, TSH, Np-SH, and LHP levels were decreased in the brain tissue of aged rats given LA supplementation. The levels of the same parameters were not significantly different in the skeletal muscle tissue of aged rats given LA supplementation. The increased levels of protein oxidation markers such as PCO, and NT in the brain tissue of LA-supplemented aged rats compared with non-supplemented aged rats may suggest that oxidative protein damage is increased in LA-supplemented aged rats. We assume that an explanation for our findings regarding LA supplementation on protein oxidation markers in the brain tissue of aged rats may be due to the prooxidant effects of LA. Depending on post-mitotic tissue type and dosage of LA, the prooxidant effects of LA supplementation, should be considered in future studies.

Creatine monohydrate supplemented in swine finishing diets and fresh pork quality: III. Evaluating the cumulative effect of creatine monohydrate and alpha-lipoic acid.

The objective of this study was to evaluate short-duration supplementation of alpha-lipoic acid (ALA) and creatine monohydrate (CMH) to improve fresh pork quality. Forty-eight commercial hybrid barrows were blocked by BW and randomly allotted to one of four treatments: 1) no CMH or ALA; 2) supplementation of 24 g of CMH(-1) x pig(-1) x d(-1); 3) supplementation of 600 mg ALA(-1) x pig(-1) x d(-1); or 4) combined CMH and ALA supplements. Twelve pigs per treatment were individually penned with ad libitum access to water and a finishing diet. Treatments were hand-fed to individual pigs daily (divided into three equal doses) for 5 d before slaughter at 113 kg BW in two separate groups of 24 pigs each. Intramuscular pH was recorded at 45 min postmortem and again at 24 h in the ham semimembranosus (SM) and the longissimus muscle (LM) between the 10th and 11th rib. A Meatcheck (SFK Technology, Peosta, IA) conductivity probe was inserted in the same anatomical locations as pH measurement, providing an index value (PY) from 0 to 100 (a higher index value indicates more intact muscle cells and higher water-holding capacity). Color (L, a, b values) measurements were obtained at 24 h postmortem on the ham gluteus medius (GM), SM, and LM. Two 2.54-cm-thick loin chops were removed from the loin for determination of Warner-Bratzler shear force and glycolytic potential. The intact SM and the posterior portion of the boneless loin were vacuum-packaged and stored for 7 d to determine purge loss. Creatine-supplemented pigs had a higher (P = 0.03) PY value in the SM (66.67) at 45 min postmortem than either ALA, singularly (63.50), or in the combined CMH/ALA (62.27) treatments. (A higher PY index indicates superior water-holding capacity.) Lipoic acid supplementation resulted in the highest pH at 45 min (P = 0.029). These results justify further evaluation of the potential positive influence of supplementing alpha-lipoic acid to improve pork quality.

Salt-induced hypertension in WKY rats: prevention by alpha-lipoic acid supplementation.

There is strong evidence that points to excess dietary salt as a major factor contributing to the development of hypertension. Salt sensitivity is associated with glucose intolerance and insulin resistance in both animal models and humans. In insulin resistance, impaired glucose metabolism leads to elevated endogenous aldehydes which bind to vascular calcium channels, increasing cytosolic [Ca2+]i and blood pressure. In an insulin resistant animal model of hypertension, spontaneously hypertensive rats (SHRs), dietary supplementation with lipoic acid lowers tissue aldehydes and plasma insulin levels and normalizes blood pressure. The objective of this study is to examine the effects of a high salt diet on tissue aldehydes, cytosolic [Ca2+]i and blood pressure in WKY rats and to investigate whether dietary supplementation with lipoic acid can prevent a salt induced increase in blood pressure. Starting at 7 weeks of age, WKY rats were divided into three groups of six animals each and treated for 10 weeks with diets as follows: WKY-normal salt (0.7% NaCl); WKY-high salt (8% NaCl); WKY-high salt + lipoic acid (8% NaCl diet + lipoic acid 500 mg/Kg feed). At completion, animals in the high salt group had elevated systolic blood pressure, platelet [Ca2+]i, and tissue aldehyde conjugates compared with the normal salt group and showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary alpha-lipoic acid supplementation in high salt-treated WKY rats normalized systolic blood pressure and cytosolic [Ca2+]i and aldehydes in liver and aorta. Kidney aldehydes and renal vascular changes were attenuated, but not normalized.

Effect of alpha-lipoic acid on lipid peroxidation and anti-oxidant enzyme activities in diabetic rats.

1. Oxidative damage has been suggested to be a contributory factor in the development and complications of diabetes. Recently, alpha-lipoic acid (ALA) has gained considerable interest as an anti-oxidant. Various studies have indicated the anti- oxidant effects of ALA and its reduced form dihydrolipoic acid. Therefore, it appears that these compounds have important therapeutic potential in conditions where oxidative stress is involved. The aim of the present study was to investigate the effect of ALA supplementation on lipid peroxidation and anti-oxidant enzyme activities in various tissues in diabetic rats. 2. Male Wistar rats were divided into three groups. Diabetes was induced by streptozotocin (STZ) injection in the two groups of rats to be supplemented and not to be supplemented with ALA. Another group of rats, which received saline injection, formed the control group. After 5 weeks of diabetes, rats were killed. In order to assess the redox status of various organs in the diabetic and control rats, thiobarbituric acid-reactive substances (TBARS) and glutathione (GSH) levels, as well as superoxide dismutase (SOD), glutathione peroxidase (G-Px) and glutathione reductase (G-Red) activities were determined in the liver, pancreas and kidney. 3. In both diabetic groups, TBARS levels and SOD activity were increased in the liver and pancreas, G-Px and G-Red activities were increased in the kidney and GSH levels were decreased in all organs compared with controls. In the ALA- supplemented group, TBARS levels were decreased, GSH levels were increased in the liver and pancreas, SOD activity was decreased in the liver, G-Px activity remained unchanged in all tissues and G-Red activity was increased in the pancreas compared with the diabetic group that did not receive ALA supplementation. 4. In conclusion, ALA supplementation has disparate effects on the redox status of different organs. These data are not sufficient for confirmation the beneficial effects of ALA supplementation on the redox status of various organs in diabetic rats.

Effect of alpha-lipoic acid supplementation on oxidative protein damage in the streptozotocin-diabetic rat.

An increase in oxidative stress may contribute to the development of oxidative protein damage in streptozotocin diabetic rats. In the present study, the influence of alpha-lipoic acid supplementation on plasma protein carbonyl, plasma thiol, and plasma lipid hydroperoxide levels was examined in order to characterize the relationship between the oxidative stress and the oxidative protein damage. Rats were randomly divided into three groups of equal body weight. Chronic hyperglycemia was induced by intravenous streptozotocin injection in both the group of male Wistar rats to be supplemented with alpha-lipoic acid and the group that was not to receive alpha-lipoic acid. Nondiabetic rats formed the control group and received a saline injection. In streptozotocin diabetic rats with and without alpha-lipoic acid supplementation, plasma carbonyl levels were significantly increased, while plasma thiol levels were significantly decreased compared with those of the control group. Plasma lipid hydroperoxide levels were significantly increased in diabetic rats without alpha-lipoic acid supplementation compared with those of the controls, but the lipid hydroperoxide levels in the alpha-lipoic acid supplemented group were no different from those of the controls. In streptozotocin-diabetic rats, oxidative stress was significantly decreased in the alpha-lipoic acid-supplemented group. The results of this study suggest that alpha-lipoic acid, by decreasing oxidative stress, may be effective in preventing oxidative protein damage, which may contribute to the development of diabetic complications.

Dietary alpha-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats.

In spontaneously hypertensive rats (SHRs), excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound, N-acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The aim of the present study was to investigate whether a dietary supplementation of an endogenous fatty acid, alpha-lipoic acid, another thiol compound that is known to increase tissue cysteine and glutathione, can lower blood pressure and normalize associated biochemical and histopathological changes in SHRs. Starting at 12 weeks of age, animals were divided into three groups of six animals each. Animals in the Wistar- Kyoto (WKY) rat control group and the SHR control group were given a normal diet, and the SHR-lipoic acid group was given a diet supplemented with lipoic acid (500 mg/kg feed) for the next 9 weeks. After 9 weeks, systolic blood pressure, platelet [Ca2+]i, plasma insulin and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls as compared with WKY rat controls and the SHR lipoic acid group. SHR controls also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary alpha-lipoic acid supplementation in SHRs lowered the systolic blood pressure, cytosolic [Ca2+]i, blood glucose and insulin levels, and tissue aldehyde conjugates, and attenuated adverse renal vascular changes.

Alpha-lipoic acid: effect on glucose uptake, sorbitol pathway, and energy metabolism in experimental diabetic neuropathy.

The peripheral nerve of experimental diabetic neuropathy (EDN) is reported to be ischemic and hypoxic, with an increased dependence on anaerobic metabolism, requiring increased energy substrate stores. When glucose stores become reduced, fiber degeneration has been reported. We evaluated glucose uptake, nerve energy metabolism, the polyol pathway, and protein kinase C (PKC) activity in EDN induced by streptozotocin. Control and diabetic rats received lipoic acid (0, 10, 25, 50, 100 mg/kg). Duration of diabetes was 1 month, and alpha-lipoic acid was administered intraperitoneally 5 times per week for the final week of the experiment. Nerve glucose uptake was reduced to 60, s 37, and 30% of control values in the sciatic nerve, L5 dorsal root ganglion, and superior cervical ganglion (SCG), respectively, in rats with EDN. Alpha-lipoic acid supplementation had no effect on glucose uptake in normal nerves at any dose, but reversed the deficit in EDN, with a threshold between 10 and 25 mg/kg. Endoneurial glucose, fructose, sorbitol, and myo-inositol were measured in sciatic nerve. Alpha-lipoic acid had no significant effect on either energy metabolism or polyol pathway of normal nerves. In EDN, endoneurial glucose, fructose, and sorbitol were significantly increased, while myo-inositol was significantly reduced. Alpha-lipoic acid had a biphasic effect: it dose-dependently increased fructose, glucose, and sorbitol, peaking at 25 mg/kg, and then fell beyond that dose, and it dose-dependently increased myo-inositol. Sciatic nerve cytosolic PKC was increased in EDN. ATP, creatine phosphate, and lactate were measured in sciatic nerve and SCG. Alpha-lipoic acid prevented the reduction in SCG creatine phosphate. We conclude that glucose uptake is reduced in EDN and that this deficit is dose-dependently reversed by alpha-lipoic acid, a change associated with an improvement in peripheral nerve function.

Alpha-lipoic acid supplementation: tissue glutathione homeostasis at rest and after exercise.

Antioxidant nutrients have demonstrated potential in protecting against exercise-induced oxidative stress. alpha-Lipoic acid (LA) is a proglutathione dietary supplement that is known to strengthen the antioxidant network. We studied the effect of intragastric LA supplementation (150 mg/kg, 8 wk) on tissue LA levels, glutathione metabolism, and lipid peroxidation in rats at rest and after exhaustive treadmill exercise. LA supplementation increased the level of free LA in the red gastrocnemius muscle and increased total glutathione levels in the liver and blood. The exercise-induced decrease in heart glutathione S-transferase activity was prevented by LA supplementation. Exhaustive exercise significantly increased thiobarbituric acid-reactive substance levels in the liver and red gastrocnemius muscle. LA supplementation protected against oxidative lipid damage in the heart, liver, and red gastrocnemius muscle. This study reports that orally supplemented LA is able to favorably influence tissue antioxidant defenses and counteract lipid peroxidation at rest and in response to exercise.