Acta Biologica Hungarica

, Volume 66, Issue 3, pp 258–269 | Cite as

Antioxidative Effects of α-Lipoic Acid in the Brain, Liver and Kidneys in selected Mouse Organs Exposed to Zymosan

  • Zofia GocEmail author
  • Agnieszka Greń
  • Edyta Kapusta
  • Karol Dziubek
  • Waldemar Szaroma


This study investigated the role of exogenous α-lipoic acid (ALA) in the inflammation caused by zymosan application. Seventy-two adult male white mice were divided into twelve groups: three control groups, three Zymosan groups, three ALA groups and three groups being the combination of Zymosan and ALA. In the experimental groups, the animals were decapitated after 3, 6 and 24 hours after the injection. The activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined in the brain, liver and kidneys of the mice. After the injection of Zymosan, it was found that the activity of SOD, CAT and GSH-Px in the brain, liver and kidneys of mice was significantly lower in all time periods. The administration of ALA resulted in an opposite effect, namely, it increased the activity of the enzymes studied in the selected organs of mice. The Zymosan and ALA combination significantly inhibited the decrease in the activity of the enzymes compared with the values obtained in the groups of animals which received Zymosan only. The results of our study, using the Zymosan-induced inflammation, clearly indicate that ALA is an anti-inflammatory agent.


Superoxide dismutase glutathione peroxidase catalase a-lipoic acid Zymosan 



a-lipoic acid


analysis of variance


bovine serum albumin


body weight




dihydrolipoic acid


ethylenediaminetetra acetic acid disodium salt


reduced glutathione


glutathione peroxidase


hydrogen peroxide


hydroxyl radical


hypochlorous acid


intraperitoneal injection


dipotassium hydrogen phosphate


potassium dihydrogen phosphate


DL-a-lipoic acid


nitric oxide




polyunsaturated fatty acids


reactive nitrogen species


reactive oxygen species


singled oxygen


superoxide dis-mutase


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  1. 1.
    Aebi, H. E. (1984) Catalase. In: Bergmeyer, H. U. (ed.) Methods of Enzymatic Analysis. Vol. 3. Wiley, New York, pp. 273–286.Google Scholar
  2. 2.
    Akpinar, D., Yargiçoglu, P., Derin, N., Alicigüzel, Y., Agar, A. (2008) The effect of lipoic acid on antioxidant status and lipid peroxidation in rats exposed to chronic restraint stress. Physiol. Res. 57, 893–901.PubMedGoogle Scholar
  3. 3.
    Antczak, A., Nomak, D., Shariati, B., Król, M., Piasecka, G., Kurmanowska, Z. (1997) Increased hydrogen peroxide and thiobarbituric acid reactive products in expired breath condensate of asthmatic patients. Eur. Respir. J. 10, 1235–1241.PubMedGoogle Scholar
  4. 4.
    Biewenga, G. P., Haenen, G. R., Bast, A. (1997) The pharmacology of the antioxidant lipoic acid. Gen. Pharmacol. 29, 315–331.PubMedGoogle Scholar
  5. 5.
    Bradford, M. M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle for protein-dye binding. Anal Biochem. 72, 248–254.Google Scholar
  6. 6.
    Bustamante, J., Lodge, J. K., Marcocci, L., Tritschler, H. J., Packer, L., Rihn, B. H. (1998) Alphalipoic acid in liver metabolism and disease. Free Rad. Biol. Med. 24, 1023–1039.PubMedGoogle Scholar
  7. 7.
    Butterfield, A. D., Reed, T., Newman, S. F., Sultana, R. (2007) Roles of amyloid ß-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer’s disease and mild cognitive impairment. Free Rad. Biol. Med. 43, 658–677.PubMedGoogle Scholar
  8. 8.
    Chen, P., Ma, Q. G., Ji, C., Zhang, J. Y., Zhao, L. H., Zhang, Y., Jie, Y. (2011) Dietary lipoic acid influences antioxidant capability and oxidative status of broilers. Int. J. Mol. Sci. 12, 8476–8488.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Cho, Y. S., Lee, J., Lee, T. H., Lee, K. U., Park, J. Y., Moon, H. B. (2002) Alpha-lipoic acid inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma. J. Allergy Clin. Immunol. 114, 429–435.Google Scholar
  10. 10.
    Crowford, M. A. (1993) The role of essential fatty acids in neural development implications for prenatal nutrition. Am. J. Clin. Nutr. 57 (Suppl), 703–710.Google Scholar
  11. 11.
    Dimitrova, P., Gyurkovska, V., Shalova, I., Saso, L., Ivanovska, N. (2009) Inhibition of zymosaninduced kidney dysfunction by tyrphostin AG-490. J. Inflamm. (Lond.) 6: 13. doi: 10.1186/1476- 9255-6-13.Google Scholar
  12. 12.
    Dulundu, E., Ozel, Y., Topaloglu, U., Sehirli, O., Ercan, F., Gedik, N., Sener, G. (2007) Alpha-lipopic acid protects against hepatic ischemia-reperfusion injury in rats. Pharmacology 79, 163–170.PubMedGoogle Scholar
  13. 13.
    Emelyanov, A., Fedoseev, G., Abulimity, A., Rudinski, K., Fedoulov, A., Karabanov, A., Barnes, P. J. (2001) Elevated concentrations of exhaled hydrogen peroxide in asthmatic patients. Chest 120, 1136–1139.PubMedGoogle Scholar
  14. 14.
    Feng, B., Yan, X. F., Xue, J. L., Xu, L., Wang, H. (2013) The protective effects of alpha-lipoic acid on kidneys in type 2 diabetic goto-kakisaki rats via reducing oxidative stress. Int. J. Mol. Sci. 14, 6746–6756.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Foloyd, R. A., West, M., Hensley, K. (2001) Oxidative biochemical markers; clues to understanding aging in long-lived species. Exp. Gerontol. 36, 619–640.Google Scholar
  16. 16.
    Hagen, T. M., Ingersoll, R. T., Lykkesfeldt, J., Liu, J., Wehr, C. M., Vinarsky, V., Bartholomew, J. C., Ames, A. B. (1999) (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J. 13, 411–418.PubMedGoogle Scholar
  17. 17.
    Han, D., Sen, C. K., Roy, S., Kobayashi, M. S., Tritschler, H. J., Packer, L. (1997) Protection against glutamate-induced cytotoxicity in C6 glial cells by thiol antioxidants. Am. J. Physiol. 273, R1771–R1778.PubMedGoogle Scholar
  18. 18.
    Han, D., Tritschler, H. J., Packer, L. (1995) a-Lipoic acid increases intracellular glutathione in a human T-lymphocyte Jurkat cell line. Biochem. Biophys. Res. Commun. 207, 258–264.PubMedGoogle Scholar
  19. 19.
    Impellizzeri, D., Mazzon, E., Di Paola, R., Paterniti, I., Baramanti, P., Cuzzocrea, S. (2011) Effect of NADPH-oxidase inhibitors in the experimental model of zymosan-induced shock in mice. Free Radic. Res. 45, 820–834.PubMedGoogle Scholar
  20. 20.
    Jansen, M. J., Hendriks, T., Verhofstad, A. A., Lange, W., Geeraedts, L. M., Jr., Goris, R. J. (1997) Gradual development of organ damage in the murine zymosan-induced multiple organ dysfunction syndrome. Shock 8, 261–267.PubMedGoogle Scholar
  21. 21.
    Janssen-Heininger, Y. M., Mossman, B. T., Heintz, N. H., Forman, H. J., Kalyanaraman, B., Finkel, T., Stamler, J. S., Rhee, S. G., van der Vliet, A. (2008) Redox-based regulation of signal transduction: principles, pitfalls, and promises. Free Radic. Biol. Med. 45, 1–17.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Kagan, V. E., Shvedova, A., Serbinova, E., Khan, S., Swanson, C., Powell, R., Packer, L. (1992) Dihydrolipoic - a universal antioxidant both in the membrane and in the aqueous phase. Reduction of peroxyl, ascorbyl and chromanoxyl radicals. Biochem. Pharmacol. 44, 1637–1649.PubMedGoogle Scholar
  23. 23.
    Kitada, M., Kume, S., Imaizumi, N., Koya, D. (2011) Resveratrol improves oxidative stress and protects against diabetic nephropathy through normalization of Mn-SOD dysfunction in AMPK/SIRT1- independent pathway. Diabetes 60, 634–643.PubMedCentralGoogle Scholar
  24. 24.
    Kubo, K., Saito, M., Tadocoro, T., Maekawa, A. (1997) Changes in susceptibility of tissues to lipid peroxidation after ingestion of various levels of docosahexanoic acid and vitamin E. Br. J. Nutr. 78, 655–669.Google Scholar
  25. 25.
    Le Bras, M., Clément, M. V., Pervaiz, S., Brenner, C. (2005) Reactive oxygen species and the mitochondrial signaling pathway of cell death. Histol. Histopathol. 20, 205–219.Google Scholar
  26. 26.
    Li, C., Zhou, H. M. (2011) The role of manganese superoxide dismutase in inflammation defense. Enzyme Res. 2011, 387176. doi: 10.4061/2011/387176.PubMedCentralGoogle Scholar
  27. 27.
    Li, H., Gonnella, P., Safavi, F., Vessal, G., Nourbakhsh, B., Zhou, F., Zhang, G. X., Rostami, A. (2013) Low dose zymosan ameliorates both chronic and relapsing experimental autoimmune encephalomyelitis. J. Neuroimmunol. 254, 28–38.PubMedGoogle Scholar
  28. 28.
    Liang, H., Ran, Q., Jang, Y. C., Holstein, D., Lechleiter, J., McDonald-Marsh, T., Musatov, A., Song, W., Van Remmen, H., Richardson, A. (2009) Glutathione peroxidase 4 differentially regulates the release of apoptogenic proteins from mitochondria. Free Radic. Biol. Med. 47, 312–320.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Lück, H. (1962) Peroxidase. In: Bergmeyer, H. U. (ed.) Methoden der enzymatischen Analyse. Verlag Chemie GmbH, Weinheim, pp. 895–897.Google Scholar
  30. 30.
    Moini, H., Packer, L., Saris, N. E. (2002) Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid. Toxicol. Appl. Pharmacol. 182, 84–90.PubMedGoogle Scholar
  31. 31.
    Mruk, D. D., Silvestrini, B., Mo, M. Y., Cheng, C. Y. (2002) Antioxidant superoxide dismutase-a review: its function, regulation in the testis, and role in male fertility. Contraception 65, 305–311.PubMedGoogle Scholar
  32. 32.
    Odabasoglu, F., Halici, Z., Aygun, H., Halici, M., Atalay, F., Cakir, A., Cadirci, E., Bayir, Y., Suleyman, H. (2011) a-Lipoic acid has anti-inflammatory and anti-oxidative properties: an experimental study in rats with carrageenan-induced acute and cotton pellet-induced chronic inflammations. Br. J. Nutr. 105, 31–43.PubMedGoogle Scholar
  33. 33.
    Packer, L., Kraemer, K., Rimbach, G. (2001) Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 17, 888–895.PubMedGoogle Scholar
  34. 34.
    Pillai, C. K., Pillai, K. S. (2002) Antioxidants in health. Indian J. Physiol. Pharmacol. 46, 1–5.PubMedGoogle Scholar
  35. 35.
    Pini, M., Gove, M. E., Senello, J. A., van Baal, J. W. P. M., Chan, L., Fantuzzi, G. (2008) Role and regulation of adipokines during zymosan-induced peritoneal inflammation in mice. Endocrinology 149, 4080–4085.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Podda, M., Tritschler, H. J., Ulrich, H., Packer, L. (1994) Alpha-lipoic acid supplementation prevents symptoms of vitamin E deficiency. Biochem. Biophys. Res. Commun. 14, 98–104.Google Scholar
  37. 37.
    Rice-Evans, C. A., Diplock, A. T., Symons, M. C. R. (1991) Techniques in free radicals research. In: Burdon, R. H., van Knippenberg, P. H. (eds) Laboratory Techniques in Biochemistry and Molecular Biology. Elsevier, Amsterdam, London, New York, Tokyo.Google Scholar
  38. 38.
    Sahach, V. F., Kakhanovs’kyu, E. F., Horbovets, V. S. (2008) The mitochondrial permeability transition pore opening under oxidative stress in ischemia/reperfusion in the tissue of the lower extremities. Fiziol. Zh. 54, 47–51.PubMedGoogle Scholar
  39. 39.
    Santos, R. C., Moresco, R. N., Peña Rico, M. A., Susperregui, A. R., Rosa, J. L., Bartrons, R., Ventura, F., Mário, D. N., Alves, S. H., Tatsch, E., Kober, H., de Mello, R. O., Scherer, P., de Oliveira, J. R. (2012) Fructose-1, 6-bisphosphate protects against zymosan-induced acute lung injury in mice. Inflammation 35, 1198–1203.PubMedGoogle Scholar
  40. 40.
    Selvakumar, E., Prahalathan, C., Mythili, Y., Varalakshmi, P. (2005) Beneficial effects of DL-a-lipoic acid on cyclophosphamide-induced oxidative stress in mitochondrial fractions of rat testis. Chem. Biol. Interact. 152, 59–66.PubMedGoogle Scholar
  41. 41.
    Sen, C. K. (1997) Nutritional biochemistry of cellular glutathione. J. Nutr. Biochem. 8, 660–672.Google Scholar
  42. 42.
    Smith, A. R., Shenvi, S. V., Widlansky, M., Suh, J. H., Hagen, T. M. (2004) Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr. Med. Chem. 11, 1135–1146.PubMedGoogle Scholar
  43. 43.
    Szaroma, W., Dziubek, K. (2011) Changes in the amount of reduced glutathione and activity of antioxidant enzymes in chosen mouse organs influenced by zymosan and melatonin administration. Acta Biol. Hung. 62, 133–141.PubMedGoogle Scholar
  44. 44.
    Takenaka, M., Kanada, S., Hamazaki, T., Watanabe, S. (2005) Dietary supplementation with n-3 polyunsaturated fatty acids attenuates the depression of food-motivated behavior during zymosaninduced peritonitis. Biol. Pharm. Bull. 28, 1291–1293.PubMedGoogle Scholar
  45. 45.
    Zygmunt, M., Dudek, M., Bilska-Wilkosz, A., Bednarski, M., Mogilski, Sz., Knutelska, J., Sapa, J. (2013) Anti-inflammatory activity of lipoic acid in mice peritonitis model. Acta Pol. Pharm. 70, 899–904.Google Scholar

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© Akadémiai Kiadó, Budapest 2015

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Authors and Affiliations

  • Zofia Goc
    • 1
    Email author
  • Agnieszka Greń
    • 1
  • Edyta Kapusta
    • 1
  • Karol Dziubek
    • 1
  • Waldemar Szaroma
    • 1
  1. 1.Department of Animal Physiology and Toxicology, Institute of BiologyPedagogical University of CracowCracowPoland

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