Cookies Notification

We use cookies to improve your website experience. To learn about our use of cookies and how you can manage your cookie settings, please see our Cookie Policy.
×

Alpha-lipoic acid: molecular mechanisms and therapeutic potential in diabetes

Publication: Canadian Journal of Physiology and Pharmacology
25 September 2015

Abstract

Diabetes is a chronic metabolic disease with a high prevalence worldwide. Diabetes and insulin resistance are associated with the development of cardiovascular and nervous diseases. The development of these disorders reflects complex pathological processes in which the oxidative stress caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) plays a pivotal role. It is widely accepted that diabetes impairs endothelial nitric oxide synthase (eNOS) activity and increases the production of ROS, thus resulting in diminished NO bioavailability and increased oxidative stress. Alpha-lipoic acid (LA) possesses beneficial effects both in the prevention and in the treatment of diabetes. LA is a potent antioxidant with insulin-mimetic and anti-inflammatory activity. LA in the diet is quickly absorbed, transported to the intracellular compartments, and reduced to dihydrolipoic acid (DHLA) under the action of enzymes. LA, which plays an essential role in mitochondrial bioenergetic reactions, has drawn considerable attention as an antioxidant for use in managing diabetic complications such as retinopathy, neuropathy and other vascular diseases.

Résumé

Le diabète est un désordre métabolique chronique avec une prévalence élevée à travers le monde. Cette pathologie et la résistance à l’insuline sont associées au développement d’atteintes cardiovasculaires et nerveuses. Le développement de ces atteintes reflète des processus pathologiques complexes mettant en jeu un stress oxydatif qui joue un rôle majeur en impliquant les espèces radicalaires oxygénées (ERO) et nitro-oxygénées (ERN). Il est généralement admis que le diabète modifie l’activité des oxyde nitrique synthases endothéliales (eNOS), conduisant à une diminution de la biodisponibilité du NO et une augmentation du stress oxydatif. L’acide alpha-lipoïque (AL) possède des effets bénéfiques dans la prévention et le traitement du diabète. AL est un antioxydant puissant pourvu d’activités insulino-mimétiques et anti-inflammatoires. AL présent dans la nourriture est rapidement absorbé, transporté dans les compartiments intracellulaires et réduit en acide dihydrolipoïque (ADHL) sous l’effet d’enzymes. AL qui joue un rôle essentiel dans les réactions bioénergétiques mitochondriales, suscite beaucoup d’attention comme antioxydant dans la prise en charge des complications liées au diabète telles que les rétinopathies, les neuropathies et les autres atteintes vasculaires.

Get full access to this article

View all available purchase options and get full access to this article.

References

Abbott K., Basta E., and Bakris G.L. 2004. Blood pressure control and nephroprotection in diabetes. J. Clin. Pharmacol. 44(4): 431–438.
Anuranjani and Bala M. 2014. Concerted action of Nrf2-ARE pathway, MRN complex, HMGB1 and inflammatory cytokines: implication in modification of radiation damage. Redox Biol. 2: 832–846.
Applegate M.A., Humphries K.M., and Szweda L.I. 2008. Reversible inhibition of alpha-ketoglutarate dehydrogenase by hydrogen peroxide: glutathionylation and protection of lipoic acid. Biochemistry, 47(1): 473–478.
Chan K.H., Ng M.K., and Stocker R. 2011. Haem oxygenase-1 and cardiovascular disease: mechanisms and therapeutic potential. Clin. Sci. (Lond.), 120(12): 493–504.
Chernyak B.V. and Bernardi P. 1996. The mitochondrial permeability transition pore is modulated by oxidative agents through both pyridine nucleotides and glutathione at two separate sites. Eur. J. Biochem. 238(3): 623–630.
Dinkova-Kostova A.T. and Talalay P. 2008. Direct and indirect antioxidant properties of inducers of cytoprotective proteins. Mol. Nutr. Food Res. 52(Suppl. 1): S128–S138.
El Midaoui A. and de Champlain J. 2002. Prevention of hypertension, insulin resistance, and oxidative stress by alpha-lipoic acid. Hypertension, 39(2): 303–307.
Fong D.S., Aiello L., Gardner T.W., King G.L., Blankenship G., Cavallerano J.D., et al; American Diabetes Association 2004. Retinopathy in diabetes. Diabetes Care, 27(Suppl. 1): S84–S87.
Fritz K.S. and Petersen D.R. 2013. An overview of the chemistry and biology of reactive aldehydes. Free Radic. Biol. Med. 59: 85–91.
Golbidi S., Badran M., and Laher I. 2011. Diabetes and alpha lipoic Acid. Front. Pharmacol. 2: 69.
Grassi D., Desideri G., Croce G., Tiberti S., Aggio A., and Ferri C. 2009. Flavonoids, vascular function and cardiovascular protection. Curr. Pharm. Des. 15(10): 1072–1084.
Gustafsson A.B. and Gottlieb R.A. 2008. Heart mitochondria: gates of life and death. Cardiovasc. Res. 77(2): 334–343.
Haritoglou C., Gerss J., Hammes H.P., Kampik A., and Ulbig M.W. RETIPON Study Group 2011. Alpha-lipoic acid for the prevention of diabetic macular edema. Ophthalmologica, 226(3): 127–137.
Heart Protection Study Collaborative Group 2002. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet, 360(9326): 23–33.
Hercberg S., Galan P., Preziosi P., Bertrais S., Mennen L., Malvy D., et al. 2004. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch. Intern. Med. 164(21): 2335–2342.
Javadov S. and Kuznetsov A. 2013. Mitochondrial permeability transition and cell death: the role of cyclophilin d. Front. Physiol. 4: 76.
Karim S., Adams D.H., and Lalor P.F. 2012. Hepatic expression and cellular distribution of the glucose transporter family. World J. Gastroenterol. 18(46): 6771–6781.
Khanna S., Roy S., Packer L., and Sen C.K. 1999. Cytokine-induced glucose uptake in skeletal muscle: redox regulation and the role of alpha-lipoic acid. Am. J. Physiol. 276(5): R1327–R1333.
Klein R. and Klein B.E. 1997. Diabetic eye disease. Lancet, 350(9072): 197–204.
Konrad D., Somwar R., Sweeney G., Yaworsky K., Hayashi M., Ramlal T., and Klip A. 2001. The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. Diabetes, 50(6): 1464–1471.
Koufaki, M. 2014. Therapeutic applications of lipoic acid: a patent review (2011–2014). Expert Opin. Ther. Pat. 24(9): 993–1005.
Lee W.J., Song K.H., Koh E.H., Won J.C., Kim H.S., Park H.S., et al. 2005. Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochem. Biophys. Res. Commun. 332(3): 885–891.
Lorgis L., Zeller M., Dentan G., Sicard P., Richard C., Buffet P., et al. 2010. The free oxygen radicals test (FORT) to assess circulating oxidative stress in patients with acute myocardial infarction. Atherosclerosis, 213(2): 616–621.
Lu S.C. 2013. Glutathione synthesis. Biochim. Biophys. Acta, 1830(5): 3143–3153.
Marangon K., Devaraj S., Tirosh O., Packer L., and Jialal I. 1999. Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress. Free Radic. Biol. Med. 27(9–10): 1114–1121.
Marso S.P. and Hiatt W.R. 2006. Peripheral arterial disease in patients with diabetes. J. Am. Coll. Cardiol. 47(5): 921–929.
May J.M., Qu Z.C., and Nelson D.J. 2007. Uptake and reduction of alpha-lipoic acid by human erythrocytes. Clin. Biochem. 40(15): 1135–1142.
McLain A.L., Szweda P.A., and Szweda L.I. 2011. Alpha-Ketoglutarate dehydrogenase: a mitochondrial redox sensor. Free Radic. Res. 45(1): 29–36.
Moini H., Packer L., and Saris N.E. 2002a. Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid. Toxicol. Appl. Pharmacol. 182(1): 84–90.
Moini H., Tirosh O., Park Y.C., Cho K.J., and Packer L. 2002b. R-alpha-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3T3-L1 adipocytes. Arch. Biochem. Biophys. 397(2): 384–391.
Morkunaite-Haimi S., Kruglov A.G., Teplova V.V., Stolze K., Gille L., Nohl H., and Saris N.E. 2003. Reactive oxygen species are involved in the stimulation of the mitochondrial permeability transition by dihydrolipoate. Biochem. Pharmacol. 65(1): 43–49.
Niki E. 2009. Lipid peroxidation: physiological levels and dual biological effects. Free Radic. Biol. Med. 47(5): 469–484.
Ogborne R.M., Rushworth S.A., and O’Connell M.A. 2005. Alpha-lipoic acid-induced heme oxygenase-1 expression is mediated by nuclear factor erythroid 2-related factor 2 and p38 mitogen-activated protein kinase in human monocytic cells. Arterioscler. Thromb. Vasc. Biol. 25(10): 2100–2105.
Ou P., Tritschler H.J., and Wolff S.P. 1995. Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant? Biochem. Pharmacol. 50(1): 123–126.
Packer L., Witt E.H., and Tritschler H.J. 1995. Alpha-Lipoic acid as a biological antioxidant. Free Radic. Biol. Med. 19(2): 227–250.
Packer L., Kraemer K., and Rimbach G. 2001. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition, 17(10): 888–895.
Petersen Shay K., Moreau R.F., Smith E.J., and Hagen T.M. 2008. Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity. IUBMB Life, 60(6): 362–367.
Richard J.L., Lavigne J.P., and Sotto A. 2012. Diabetes and foot infection: more than double trouble. Diabetes Metab. Res. Rev. 28(Suppl. 1): 46–53.
Rochette L., Tatou E., Maupoil V., Zeller M., Cottin Y., Jazayeri S., et al. 2011. Atrial and vascular oxidative stress in patients with heart failure. Cell. Physiol. Biochem. 27(5): 497–502.
Rochette L., Cottin Y., Zeller M., and Vergely C. 2013a. Carbon monoxide: mechanisms of action and potential clinical implications. Pharmacol. Ther. 137(2): 133–152.
Rochette L., Ghibu S., Richard C., Zeller M., Cottin Y., and Vergely C. 2013b. Direct and indirect antioxidant properties of alpha-lipoic acid and therapeutic potential. Mol. Nutr. Food Res. 57(1): 114–125.
Rochette L., Lorin J., Zeller M., Guilland J.C., Lorgis L., Cottin Y., and Vergely C. 2013c. Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: possible therapeutic targets? Pharmacol. Ther. 140(3): 239–257.
Rochette L., Zeller M., Cottin Y., and Vergely C. 2014. Diabetes, oxidative stress and therapeutic strategies. Biochim. Biophys. Acta, 1840(9): 2709–2729.
Schupke H., Hempel R., Peter G., Hermann R., Wessel K., Engel J., and Kronbach T. 2001. New metabolic pathways of alpha-lipoic acid. Drug Metab. Dispos. 29(6): 855–862.
Singh U. and Jialal I. 2008. Alpha-lipoic acid supplementation and diabetes. Nutr. Rev. 66(11): 646–657.
Streeper R.S., Henriksen E.J., Jacob S., Hokama J.Y., Fogt D.L., and Tritschler H.J. 1997. Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle. Am. J. Physiol. 273(1): E185–E191.
Suh J.H., Shenvi S.V., Dixon B.M., Liu H., Jaiswal A.K., Liu R.M., and Hagen T.M. 2004. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc. Natl. Acad. Sci. U.S.A. 101(10): 3381–3386.
Suh J.H., Moreau R., Heath S.H., and Hagen T.M. 2005. Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep. 10(1): 52–60.
Trujillo M. and Radi R. 2002. Peroxynitrite reaction with the reduced and the oxidized forms of lipoic acid: new insights into the reaction of peroxynitrite with thiols. Arch. Biochem. Biophys. 397(1): 91–98.
Valdecantos M.P., Perez-Matute P., Gonzalez-Muniesa P., Prieto-Hontoria P.L., Moreno-Aliaga M.J., and Martinez J.A. 2012. Lipoic acid administration prevents nonalcoholic steatosis linked to long-term high-fat feeding by modulating mitochondrial function. J. Nutr. Biochem. 23(12): 1676–1684.
Vasdev S., Gill V., Parai S., and Gadag V. 2005. Dietary lipoic acid supplementation attenuates hypertension in Dahl salt sensitive rats. Mol. Cell. Biochem. 275(1–2): 135–141.
Vergely C., Maupoil V., Benderitter M., and Rochette L. 1998. Influence of the severity of myocardial ischemia on the intensity of ascorbyl free radical release and on postischemic recovery during reperfusion. Free Radic. Biol. Med. 24(3): 470–479.
Vergely C., Perrin C., Laubriet A., Oudot A., Zeller M., Guilland J.C., and Rochette L. 2001. Postischemic myocardial recovery and oxidative stress status of vitamin C deficient rat hearts. Cardiovasc. Res. 51(1): 89–99.
Yaworsky K., Somwar R., Ramlal T., Tritschler H.J., and Klip A. 2000. Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by alpha-lipoic acid in 3T3-L1 adipocytes. Diabetologia, 43(3): 294–303.
Ying Z., Kampfrath T., Sun Q., Parthasarathy S., and Rajagopalan S. 2011. Evidence that alpha-lipoic acid inhibits NF-kappaB activation independent of its antioxidant function. Inflamm. Res. 60(3): 219–225.
Zhang D.D., Lo S.C., Cross J.V., Templeton D.J., and Hannink M. 2004. Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Mol. Cell. Biol. 24(24): 10941–10953.
Ziegler D. 2004. Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat. Endocrinol. 3(3): 173–189.
Ziegler D., Low P.A., Litchy W.J., Boulton A.J., Vinik A.I., Freeman R., et al. 2011. Efficacy and safety of antioxidant treatment with alpha-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care, 34(9): 2054–2060.
Zoratti M. and Szabo I. 1995. The mitochondrial permeability transition. Biochim. Biophys. Acta, 1241(2): 139–176.

Information & Authors

Information

Published In

cover image Canadian Journal of Physiology and Pharmacology
Canadian Journal of Physiology and Pharmacology
Volume 93Number 12December 2015
Pages: 1021 - 1027

History

Received: 13 September 2014
Accepted: 13 April 2015
Version of record online: 25 September 2015

Notes

This Invited Review is part of a Special Issue entitled “Pharmacology of vitamins and beyond. Part 2.”

Permissions

Request permissions for this article.

Key Words

  1. lipoic acid
  2. antioxidant
  3. diabetes
  4. metabolism
  5. prevention
  6. treatment

Mots-clés

  1. acide lipoïque
  2. antioxydant
  3. diabètes
  4. métabolisme
  5. prévention
  6. traitement

Authors

Affiliations

Luc Rochette
Laboratoire de Physiopathologie et Pharmacologies Cardio-Métaboliques (LPPCM), INSERM UMR866, Université de Bourgogne, Facultés de Médecine et de Pharmacie, 7 Boulevard Jeanne d’Arc, 21033 Dijon Cedex, France.
Steliana Ghibu [email protected]
Department of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, “UMF Iuliu Haţieganu”, 6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania.
Adriana Muresan
Department of Physiology, Faculty of Medicine, “UMF Iuliu Haţieganu” Cluj-Napoca, Romania.
Catherine Vergely
Laboratoire de Physiopathologie et Pharmacologies Cardio-Métaboliques (LPPCM), INSERM UMR866, Université de Bourgogne, Facultés de Médecine et de Pharmacie, 7 Boulevard Jeanne d’Arc, 21033 Dijon Cedex, France.

Metrics & Citations

Metrics

Other Metrics

Citations

Cite As

Export Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

Cited by

1. Parallelism and non-parallelism in diabetic nephropathy and diabetic retinopathy
2. Vitamin E/Coenzyme Q-Dependent “Free Radical Reductases”: Redox Regulators in Ferroptosis
3. Diyabet Tedavisinde Antioksidan Etki: Alfa Lipoik Asit
4. Alpha-lipoic acid for diabetic peripheral neuropathy
5. Homeostasis and dyshomeostasis of the retina
6. Antioxidant and Anti-inflammatory Effects of α-Lipoic Acid on Lipopolysaccharide-induced Oxidative Stress in Rat Kidney
7. Effectiveness of alpha-lipoic acid in patients with neuropathic pain associated with type I and type II diabetes mellitus: A systematic review and meta-analysis
8. Effect of alpha-lipoic acid and caffeine-loaded chitosan nanoparticles on obesity and its complications in liver and kidney in rats
9. Alpha-lipoic acid supplementation affects serum lipids in a dose and duration-dependent manner in different health status
10. Recent Advances in Electrochemical Sensors for Sulfur-Containing Antioxidants
11. Alpha-lipoic acid modulates the diabetes mellitus-mediated neuropathic pain via inhibition of the TRPV1 channel, apoptosis, and oxidative stress in rats
12. Low concentrations of α-lipoic acid reduce palmitic acid-induced alterations in murine hypertrophic adipocytes
13. Food Antioxidants and Their Interaction with Human Proteins
14. Untargeted Metabolomics by Ultra-High-Performance Liquid Chromatography Coupled with Electrospray Ionization-Quadrupole-Time of Flight-Mass Spectrometry Analysis Identifies a Specific Metabolomic Profile in Patients with Early Chronic Kidney Disease
15. Renal-Protective Roles of Lipoic Acid in Kidney Disease
16. Alleviative effects of α‐lipoic acid on muscle atrophy via the modulation of TNF ‐α/ JNK and PI3K / AKT pathways in high‐fat diet and streptozotocin‐induced type 2 diabetic rats
17. Metabolic Mechanisms in Diabetic Neuropathy
18. Alpha-Lipoic Acid as an Antioxidant Strategy for Managing Neuropathic Pain
19. RETRACTED ARTICLE: Alpha-Lipoic Acid Protects Against Doxorubicin-Induced Cardiotoxicity by Regulating Pyruvate Dehydrogenase Kinase 4
20. Protective Effects of Alpha-Lipoic Acid against 5-Fluorouracil-Induced Gastrointestinal Mucositis in Rats
21. α-lipoic acid ameliorates inflammation state and oxidative stress by reducing the content of bioactive lipid derivatives in the left ventricle of rats fed a high-fat diet
22. Potential diabetic cardiomyopathy therapies targeting pyroptosis: A mini review
23. α-Lipoic Acid Protects against Cyclosporine A-Induced Hepatic Toxicity in Rats: Effect on Oxidative Stress, Inflammation, and Apoptosis
24. R- Is Superior to S-Form of α-Lipoic Acid in Anti-Inflammatory and Antioxidant Effects in Laying Hens
25. Strategic application of liposomal system to R-α-lipoic acid for the improvement of nutraceutical properties
26. Alpha-lipoic acid potentiates the anti-arrhythmic effects of ischemic postconditioning in the setting of cardiac ischemia/reperfusion injury in diabetic rats
27. Efficacy and safety of the combined metabolic medication, containing inosine, nicotinamide, riboflavin and succinic acid, for the treatment of diabetic neuropathy: a multicenter randomized, double-blind, placebo-controlled parallel group clinical trial (CYLINDER)
28. Sphingolipid metabolism plays a key role in diabetic peripheral neuropathy
29. Treatment for Diabetic Peripheral Neuropathy: What have we Learned from Animal Models?
30. Stress degradation studies and development of validated stability indicating densitometric method for estimation of alpha lipoic acid in bulk and capsule dosage form
31. Alpha lipoic acid decreases neuronal damage on brain tissue of STZ-induced diabetic rats
32. Encapsulation of Alpha-Lipoic Acid in Functional Hybrid Liposomes: Promising Tool for the Reduction of Cisplatin-Induced Ototoxicity
33. α-Lipoic Acid Strengthens the Antioxidant Barrier and Reduces Oxidative, Nitrosative, and Glycative Damage, as well as Inhibits Inflammation and Apoptosis in the Hypothalamus but Not in the Cerebral Cortex of Insulin-Resistant Rats
34. Diabetic neuropathy in combination with deficiency state
35. Recent Insights into the Nutritional Antioxidant Therapy in Prevention and Treatment of Diabetic Vascular Complications: A Comprehensive Review
36. Exercise Performance Upregulatory Effect of R-α-Lipoic Acid with γ-Cyclodextrin
37. Recent developments of neuroprotective agents for degenerative retinal disorders
38. α-Lipoic Acid Reduces Ceramide Synthesis and Neuroinflammation in the Hypothalamus of Insulin-Resistant Rats, While in the Cerebral Cortex Diminishes the β-Amyloid Accumulation
39. Therapeutic applications of low-molecular-weight thiols and selenocompounds
40. Efficiency of “Neo inulin” in the complex treatment of patients with type 2 diabetes
41. Epigenetic modifying potential of Lipoic acid: Implications in curing diabetes
42. Effect of alpha-lipoic acid on oxidative stress parameters: A systematic review and meta-analysis
43. Safety and efficacy of alpha-lipoic acid oral supplementation in the reduction of pain with unknown etiology: A monocentric, randomized, double-blind, placebo-controlled clinical trial
44. Boron-based hybrids as novel scaffolds for the development of drugs with neuroprotective properties
45. The Role of Alpha-lipoic Acid Supplementation in the Prevention of Diabetes Complications: A Comprehensive Review of Clinical Trials
46. Effects of Lipoic Acid on Ischemia-Reperfusion Injury
47. Alpha-lipoic acid attenuates silica-induced pulmonary fibrosis by improving mitochondrial function via AMPK/PGC1α pathway activation in C57BL/6J mice
48. Mechanics Insights of Alpha-Lipoic Acid against Cardiovascular Diseases during COVID-19 Infection
49. Sodium R-lipoate and enzymatically-modified isoquercitrin suppressed IgE-independent anaphylactic reactions and stress-induced gastric ulceration in mice
50. Antioxidant Properties of Alpha-Lipoic (Thioctic) Acid Treatment on Renal and Heart Parenchyma in a Rat Model of Hypertension
51. Synthesis and study of new indoline spiropyran and its derivative with α-lipoic acid exhibiting low cytotoxicity
52. Nanoparticles of lipoic acid esters: preparation and antioxidant effect
53. The role of biofactors in the prevention and treatment of age‐related diseases
54. The role of alpha lipoic acid in female and male infertility: a systematic review
55. Hyperosmolarity Triggers the Warburg Effect in Chinese Hamster Ovary Cells and Reveals a Reduced Mitochondria Horsepower
56. Alpha lipoic acid improves heat stress-induced reduction of serum oestradiol and progesterone levels by affecting oxidative and endoplasmic reticulum stress in hens
57. The mechanism and prevention of mitochondrial injury after exercise
58. An updated systematic review and dose-response meta-analysis of the effects of α-lipoic acid supplementation on glycemic markers in adults
59. Antioxidants with hepatoprotective activity
60. Novel molecular hybrids of indoline spiropyrans and α-lipoic acid as potential photopharmacological agents: Synthesis, structure, photochromic and biological properties
61. Oxidative stress mitigation by antioxidants - An overview on their chemistry and influences on health status
62. Are Reactive Sulfur Species the New Reactive Oxygen Species?
63. Chapter 51: Natural Products
64. Alpha-lipoic acid improves sperm motility in infertile men after varicocelectomy: a triple-blind randomized controlled trial
65. Alpha‐lipoic acid: A possible pharmacological agent for treating dry eye disease and retinopathy in diabetes
66. Protective Effects of a Discontinuous Treatment with Alpha-Lipoic Acid in Obesity-Related Heart Failure with Preserved Ejection Fraction, in Rats
67. Estimation of Lipoyllysine Content in Meat and Its Antioxidative Capacity
68. Lipoic acid rejuvenates aged intestinal stem cells by preventing age‐associated endosome reduction
69. Diabetes and calcification: The potential role of anti-diabetic drugs on vascular calcification regression
70. Adrenomedullin expression in aortic artery wall of diabetic rats given alpha lipoic acid
71. Management of Diabetes and Nutritional Supplements
72. Alpha-lipoic acid inhibits proliferation and migration of human vascular endothelial cells through downregulating HSPA12B/VEGF signaling axis
73. Alpha‐lipoic acid inhibits lung cancer growth via mTOR‐mediated autophagy inhibition
74. The effects of alpha lipoic acid on muscle strength recovery after a single and a short-term chronic supplementation - a study in healthy well-trained individuals after intensive resistance and endurance training
75. Protective effect of alpha-lipoic acid and omega-3 fatty acids against cyclophosphamide-induced ovarian toxicity in rats
76.
77. Diabetes Mellitus Types I and II
78. Polycystic Ovary Syndrome (PCOS)
79. Dual Character of Reactive Oxygen, Nitrogen, and Halogen Species: Endogenous Sources, Interconversions and Neutralization
80. Are the beneficial effects of ‘antioxidant’ lipoic acid mediated through metabolism of reactive sulfur species?
81. Assessment of the efficacy of α-lipoic acid in treatment of diabetes mellitus patients with erectile dysfunction
82. Impact of Alpha-Lipoic Acid Chronic Discontinuous Treatment in Cardiometabolic Disorders and Oxidative Stress Induced by Fructose Intake in Rats
83. Biomarkers of response to alpha-lipoic acid ± palmitoiletanolamide treatment in patients with diabetes and symptoms of peripheral neuropathy
84. The Effects of a Novel Series of KTTKS Analogues on Cytotoxicity and Proteolytic Activity
85. Effect of alpha-lipoic acid at the combination with mefenamic acid in girls with primary dysmenorrhea: randomized, double-blind, placebo-controlled clinical trial
86. Effect of Curcumin and α-Lipoic Acid in Attenuating Weight Gain and Adiposity
87. Oxidative Stress as the Main Target in Diabetic Retinopathy Pathophysiology
88. Alpha lipoic acid and metformin alleviates experimentally induced insulin resistance and cognitive deficit by modulation of TLR2 signalling
89. Insights on the Use of α-Lipoic Acid for Therapeutic Purposes
90. The first method for determination of lipoyllysine in human urine after oral lipoic acid supplementation
91. Neurological complications of diabetes mellitus
92. Insights on alpha lipoic and dihydrolipoic acids as promising scavengers of oxidative stress and possible chelators in mercury toxicology
93. Alpha Lipoic Acid Improves Endothelial Function and Oxidative Stress in Mice Exposed to Chronic Intermittent Hypoxia
94. Alpha lipoic acid protects against dexamethasone-induced metabolic abnormalities via APPL1 and PGC-1 α up regulation
95. Elevation of the adiponectin/leptin ratio in women with gestational diabetes mellitus after supplementation with alpha-lipoic acid
96. Impaired HPA axis function in diabetes involves adrenal apoptosis and phagocytosis
97. Effect of alpha-lipoic acid supplementation on lipid profile: A systematic review and meta-analysis of controlled clinical trials
98. Progesterone, Lipoic Acid, and Sulforaphane as Promising Antioxidants for Retinal Diseases: A Review
99. Untargeted metabolomic analysis in non-fasted diabetic dogs by UHPLC–HRMS
100. Multilayered Interplay Between Fructose and Salt in Development of Hypertension
101. Reduction in maternal serum values of glucose and gamma‐glutamyltransferase after supplementation with alpha‐lipoic acid in women with gestational diabetes mellitus
102. DIABETIC NEUROPATHY: MOLECULAR MECHANISMS OF DEVELOPMENT AND POSSIBILITIES FOR PATHOGENETIC THERAPY
103. Chemical Protectors against the Toxic Effects of Paracetamol (Acetaminophen) and Its Meta Analogue: Preventing Protein Arylation
104. Regulation of aging and oxidative stress pathways in aged pancreatic islets using alpha-lipoic acid
105. Antibodies to post-translationally modified mitochondrial peptide PDC-E2(167–184) in type 1 diabetes
106. Poly(ADP-ribose) polymerase-2 is a lipid-modulated modulator of muscular lipid homeostasis
107. Alpha-Lipoic Acid improves the testicular dysfunction in rats induced by varicocele
108. The Potential Role of Fatty Acids in Treating Diabetic Neuropathy
109. Comparison of peripheral nerve protection between insulin-based glucose control and alpha lipoic acid (ALA) in the streptozotocin (STZ)-induced diabetic rat
110. A New Approach to Treating Neurodegenerative Otologic Disorders
111. ROS and RNS signalling: adaptive redox switches through oxidative/nitrosative protein modifications
112. Effect of Alpha-Lipoic Acid on Clinical and Neurophysiologic Recovery of Carpal Tunnel Syndrome: A Double-Blind, Randomized Clinical Trial
113. Alpha-lipoic acid for diabetic peripheral neuropathy
114. Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems
115. Insulin autoimmune syndrome in an Argentine woman taking α-lipoic acid: A case report and review of the literature
116. Chapter 51: Natural Products
117. In Vivo Roles of Fatty Acid Biosynthesis Enzymes in Biosynthesis of Biotin and α-Lipoic Acid in Corynebacterium glutamicum
118. Nutraceutical Effects on Glucose and Lipid Metabolism in Patients with Impaired Fasting Glucose: A Pilot, Double-Blind, Placebo-Controlled, Randomized Clinical Trial on a Combined Product
119. Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications
120. Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model
121. Diabetic nephropathy: New insights into established therapeutic paradigms and novel molecular targets
122. Physiology and role of irisin in glucose homeostasis
123. Encapsulation of the Antioxidant R-(+)-α-Lipoic Acid in Permethylated α- and β-Cyclodextrins: Thermal and X-ray Structural Characterization of the 1:1 Inclusion Complexes
124. Chronic treatment of (R)‐ α ‐lipoic acid reduces blood glucose and lipid levels in high‐fat diet and low‐dose streptozotocin‐induced metabolic syndrome and type 2 diabetes in Sprague‐Dawley rats
125. Regeneration of glutathione by α-lipoic acid via Nrf2/ARE signaling pathway alleviates cadmium-induced HepG2 cell toxicity
126. Epigenetic Treatment of Persistent Viral Infections
127. Overproduction of α-Lipoic Acid by Gene Manipulated Escherichia coli
128. Effect of dietary oxidized tyrosine products on insulin secretion via the oxidative stress-induced mitochondria damage in mice pancreas
129. α-Lipoic acid as the main pharmacological drug for in- and outpatient treatment of diabetic polyneuropathy
130. Lipoic acid protects gastric mucosa from ethanol-induced injury in rat through a mechanism involving aldehyde dehydrogenase 2 activation
131. Microbiota and Neurological Disorders: A Gut Feeling
132. A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients
133. Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases
134. Type 1 5′-deiodinase activity is inhibited by oxidative stress and restored by alpha-lipoic acid in HepG2 cells

View Options

Get Access

Login options

Check if you access through your login credentials or your institution to get full access on this article.

Subscribe

Click on the button below to subscribe to Canadian Journal of Physiology and Pharmacology

Purchase options

Purchase this article to get full access to it.

Restore your content access

Enter your email address to restore your content access:

Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

View options

PDF

View PDF

Full Text

View Full Text

Media

Media

Other

Tables

Share Options

Share

Share the article link

Share on social media