, Volume 39, Issue 1, pp 357–365 | Cite as

Alpha-Lipoic Acid Attenuates Oxidative Damage in Organs After Sepsis

  • Fabricia Petronilho
  • Drielly Florentino
  • Lucinéia Gainski Danielski
  • Luiz Carlos Vieira
  • Maryane Modolon Martins
  • Andriele Vieira
  • Sandra Bonfante
  • Mariana Pereira Goldim
  • Francieli Vuolo
Original Article


Sepsis progression is linked with the imbalance between reactive oxygen species and antioxidant enzymes. Thus, the aim of this study was to evaluate the effect of alpha-lipoic acid (ALA), a powerful antioxidant, in organs of rats submitted to sepsis. Male Wistar rats were subjected to sepsis by cecal ligation puncture (CLP) and treated with ALA or vehicle. After CLP (12 and 24 h), the myeloperoxidase (MPO) activity, protein and lipid oxidative damage, and antioxidant enzymes in the liver, kidney, heart, and lung were evaluated. ALA was effective in reducing MPO activity, lipid peroxidation in the liver, and protein carbonylation only in the kidney in 12 h after CLP. In 12 h, SOD activity increased in the kidney and CAT activity in the liver and kidney with ALA treatment. Thus, ALA was able to reduce the inflammation and oxidative stress in the liver and kidney after sepsis in rats.


sepsis alpha-lipoic acid organ failure oxidative damage 


  1. 1.
    Hotchkiss, R.S., and I.E. Karl. 2003. The pathophysiology and treatment of sepsis. The New England Journal of Medicine. 348: 138.CrossRefPubMedGoogle Scholar
  2. 2.
    Angus, D.C., W.T. Linde-Zwirble, J. Lidicker, G. Clermont, J. Carcillo, and M.R. Pinsky. 2001. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Critical Care Medicine 29: 1303–10.CrossRefPubMedGoogle Scholar
  3. 3.
    Marshall, J.C., D.J. Cook, N.V. Christou, G.R. Bernard, C.L. Sprung, and W.J. Sibbald. 1995. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Critical Care Medicine 23: 1638–52.CrossRefPubMedGoogle Scholar
  4. 4.
    Martin, G.S., D.M. Mannino, S. Eaton, and M. Moss. 2003. The epidemiology of sepsis in the United States from 1979 through 2000. The New England Journal of Medicine 348: 1546–54.CrossRefPubMedGoogle Scholar
  5. 5.
    Murugan, R., V. Karajala-Subramanyam, M. Lee, S. Yende, L. Kong, M. Carter, C.D. Angus, and J.A. Kellum. 2010. Acute kidney injury in non-severe pneumonia is associated with an increased immune response and lower survival. Kidney International 77: 527–35.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Romero-Bermejo, F.J., M. Ruiz-Bailen, J. Gil-Cebrian, and M.J. Huertos-Ranchal. 2011. Sepsis-induced cardiomyopathy. Current Cardiology Reviews 7: 163–183.PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Hochstadt, A., Y. Meroz, and G. Landesberg. 2011. Myocardial dysfunction in severe sepsis and septic shock: more questions than answers? Journal of cardiothoracic and vascular anesthesia 25: 526–35.CrossRefPubMedGoogle Scholar
  8. 8.
    Andrades, M.E., C. Ritter, and F. Dal-Pizzol. 2009. The role of free radicals in sepsis development. Frontiers in Bioscience 1: 277–87.Google Scholar
  9. 9.
    Barichello, T., J.J. Fortunato, A.M. Vitali, G. Feier, A. Reinke, J.C. Moreira, J. Quevedo, and F. Dal-Pizzol. 2006. Oxidative variables in the rat brain after sepsis induced by cecal ligation and perforation. Critical Care Medicine 34: 886–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Matsukawa, A., M.H. Kaplan, C.M. Hogaboam, N.W. Lukacs, and S.L. Kunkel. 2001. Pivotal role of signal transducer and activator of transcription (Stat)4 and Stat6 in the innate immune response during sepsis. Journal of experimental medicine 193: 679–688.PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Andrades, M., C. Ritter, M.R. de Oliveira, E.L. Streck, J.C.F. Moreira, and F. Dal-Pizzol. 2011. Antioxidant treatment reverses organ failure in rat model of sepsis: role of antioxidant enzymes imbalance, neutrophil infiltration, and oxidative stress. Journal of surgical research 167: e307–13.CrossRefPubMedGoogle Scholar
  12. 12.
    Goraca, A., H. Huk-Kolega, A. Piechota, P. Kleniewska, E. Ciejka, and B. Skibska. 2011. Lipoic acid—biological activity and therapeutic potential. Pharmacological Reports 63: 849–858.CrossRefPubMedGoogle Scholar
  13. 13.
    Abdel-Zaher, A.O., R.H. Abdel-Hady, M.M. Mahmoud, and M.M.Y. Farrag. 2008. The potential protective role of alpha-lipoic acid against acetaminophen-induced hepatic and renal damage. Toxicology 243: 261–270.CrossRefPubMedGoogle Scholar
  14. 14.
    Bilska, A., and L. Włodek. 2005. Lipoic acid—the drug of the future? Pharmacological Reports 57: 570–7.PubMedGoogle Scholar
  15. 15.
    Singh, U., and I. Jialal. 2008. Alpha-lipoic acid supplementation and diabetes. Nutrition Reviews 66: 646–657.PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Khabbazi, T., R. Mahdavi, J. Safa, and P. Pour-Abdollahi. 2012. Effects of alpha-lipoic acid supplementation on inflammation, oxidative stress, and serum lipid profile levels in patients with end-stage renal disease on hemodialysis. Journal of Renal Nutrition 22(2): 244–250.CrossRefPubMedGoogle Scholar
  17. 17.
    Kang, K.P., D.H. Kim, Y.J. Jung, A.S. Lee, S. Lee, S.Y. Lee, K.Y. Jang, M.J. Sung, S.K. Park, and W. Kim. 2009. Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation. Nephrology Dialysis Transplant 24: 3012–3020.CrossRefGoogle Scholar
  18. 18.
    Gianturco, V., A. Bellomo, E. D'Ottavio, V. Formosa, A. Iori, M. Mancinella, G. Troisi, and V. Marigliano. 2009. Impact of therapy with alpha-lipoic acid (ALA) on the oxidative stress in the controlled NIDDM: a possible preventive way against the organ dysfunction? Archives of Gerontorology and Geriatrics 49: 129–133.CrossRefGoogle Scholar
  19. 19.
    Wichterman, K.A., A.E. Baue, and I.H. Chaudry. 1980. Sepsis and septic shock—a review of laboratory models and a proposal. Journal of Surgical Research 29: 189–201.CrossRefPubMedGoogle Scholar
  20. 20.
    Fink, M.P., and S.O. Heard. 1990. Laboratory models of sepsis and septic shock. Journal of Surgical Research 49: 186–196.CrossRefPubMedGoogle Scholar
  21. 21.
    Li, G., L. Gao, J. Jia, X. Gong, B. Zang, and W. Chen. 2014. α-Lipoic acid prolongs survival and attenuates acute kidney injury in a rat model of sepsis. Clinical and Experimental Pharmacology and Physiology 41: 459–68.CrossRefPubMedGoogle Scholar
  22. 22.
    De Young, L.M., J.B. Kheifets, S.J. Ballaron, and J.M. Young. 1989. Edema and cell infiltration in the phorbol ester-treated mouse ear are temporally separate and can be differentially modulated by pharmacologic agents. Agents Action 26: 335–341.CrossRefGoogle Scholar
  23. 23.
    Esterbauer, H., and K.H. Cheeseman. 1990. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods in enzymology 186: 407–421.CrossRefPubMedGoogle Scholar
  24. 24.
    Levine, R.L., D. Garland, and C.N. Oliver. 1990. Determination of carbonyl content in oxidatively modified proteins. Methods in Enzymology 186: 464–478.CrossRefPubMedGoogle Scholar
  25. 25.
    Bannister, J.V., and L. Calabrese. 1987. Assays for superoxide dismutase. Methods of Biochemical Analysis 32: 279–312.CrossRefPubMedGoogle Scholar
  26. 26.
    Aebi, H. 1984. Catalase in vitro. Methods in Enzymology 105: 121–6.CrossRefPubMedGoogle Scholar
  27. 27.
    Lowry, O.H., N.J. Rosebrough, A.L. Farr, and R.J. Randall. 1951. Protein measurement with the Folin phenol reagent. The Journal of Biological Chemistry 193: 265–275.PubMedGoogle Scholar
  28. 28.
    Craciun, F.L., E.R. Schuller, and D.G. Remick. 2010. Early enhanced local neutrophil recruitment in peritonitis-induced sepsis improves bacterial clearance and survival. Journal of Immunology 185: 6930–8.CrossRefGoogle Scholar
  29. 29.
    Osuchowski, M.F., F. Craciun, K.M. Weixelbaumer, E.R. Duffy, and D.G. Remick. 2012. Sepsis chronically in MARS: systemic cytokine responses are always mixed regardless of the outcome, magnitude, or phase of sepsis. Journal of Immunology 189: 4648–4656.CrossRefGoogle Scholar
  30. 30.
    Oberholzer, A., C. Oberholzer, and L.L. Moldawer. 2001. Sepsis syndromes: understanding the role of innate and acquired immunity. Shock 16: 83–96.CrossRefPubMedGoogle Scholar
  31. 31.
    Yang, S., C.S. Chung, A. Ayala, I.H. Chaudry, and P. Wang. 2002. Differential alterations in cardiovascular responses during the progression of polymicrobial sepsis in the mouse. Shock 17: 55–60.CrossRefPubMedGoogle Scholar
  32. 32.
    Oberholzer, C., A. Oberholzer, M. Clare-Salzler, and L.L. Moldawer. 2001. Apoptosis in sepsis: a new target for therapeutic exploration. The FASEB Journal 15: 879–892.CrossRefPubMedGoogle Scholar
  33. 33.
    Hattori, Y., K. Takano, H. Teramae, S. Yamamoto, H. Yokoo, and N. Matsuda. 2010. Insights into sepsis therapeutic design based on the apoptotic death pathway. Journal of Pharmacological Sciences 114: 354–365.CrossRefPubMedGoogle Scholar
  34. 34.
    Olguner, C.G., U. Koca, E. Altekin, B.U. Ergür, S. Duru, P. Girgin, A. Taşdöğen, K. Gündüz, S. Güzeldağ, M. Akkuş M, et al. 2013. Ischemic preconditioning attenuates lipid peroxidation and apoptosis in the cecal ligation and puncture model of sepsis. Experimental and Therapeutic Medicine 5: 1581–1588.PubMedCentralPubMedGoogle Scholar
  35. 35.
    Tsai, K.L., H.J. Liang, Z.D. Yang, S.I. Lue, S.L. Yang, and C. Hsu. 2014. Early inactivation of PKCε associates with late mitochondrial translocation of Bad and apoptosis in ventricle of septic rat. Journal of surgical research 186: 278–286.CrossRefPubMedGoogle Scholar
  36. 36.
    Alvarez, S., and P.A. Evelson. 2007. Nitric oxide and oxygen metabolism in inflammatory conditions: sepsis and exposition to polluted ambients. Frontiers in Bioscience 12: 964–974.CrossRefPubMedGoogle Scholar
  37. 37.
    Wang, P., and I.H. Chaudry. 1996. Mechanism of hepatocellular dysfunction during hyperdynamic sepsis. American Journal of Physiology 270: R927–938.PubMedGoogle Scholar
  38. 38.
    Suh, S.H., K.E. Lee, I.J. Kim, O. Kim, C.S. Kim, J.S. Choi, H.I. Choi, E.H. Bae, S.K. Ma, J.U. Lee, et al. 2014. Alpha-lipoic acid attenuates lipopolysaccharide-induced kidney injury. Clinical and Experimental Nephrology 19: 82–91.CrossRefPubMedGoogle Scholar
  39. 39.
    Vanasco, V., M.C. Cimolai, P. Evelson, and S. Alvarez. 2008. The oxidative stress and the mitochondrial dysfunction caused by endotoxemia are prevented by alpha-lipoic acid. Free Radical Research 42: 815–823.CrossRefPubMedGoogle Scholar
  40. 40.
    Cimolai, M.C., V. Vanasco, T. Marchini, N.D. Magnani, P. Evelson, and S. Alvarez. 2014. α-Lipoic acid protects kidney from oxidative stress and mitochondrial dysfunction associated to inflammatory conditions. Food & Function 5: 3143–50.CrossRefGoogle Scholar
  41. 41.
    Safa, J., M.R. Ardalan, M. Rezazadehsaatlou, M. Mesgari, R. Mahdavi, and M.P. Jadid. 2014. Effects of alpha lipoic acid supplementation on serum levels of IL-8 and TNF-α in patient with ESRD undergoing hemodialysis. International Urology and Nephrology 46: 1633–8.CrossRefPubMedGoogle Scholar
  42. 42.
    Halliwell, B., and J.M.C. Gutteridge. 1999. Free radicals in biology and medicine. Oxford: Oxford Science.Google Scholar
  43. 43.
    Arivazhagan, P., and C. Panneerselvam. 2000. Effect of DL-alphalipoic acid on neural antioxidants in aged rats. Pharmacological Research 42: 219–222.CrossRefPubMedGoogle Scholar
  44. 44.
    Gasic-Milenkovic, J., C. Loske, and G. Munch. 2003. Advanced glycation end products cause lipid peroxidation in the human neuronal cell line SH-SY5Y. Journal of Alzheimer's Disease 5: 25–30.PubMedGoogle Scholar
  45. 45.
    Packer, L., E.H. Witt, and H.J. Tritschler. 1995. Alpha-lipoic acid as a biological antioxidant. Free Radical Biology & Medicine 19: 227–250.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Fabricia Petronilho
    • 1
  • Drielly Florentino
    • 1
  • Lucinéia Gainski Danielski
    • 1
  • Luiz Carlos Vieira
    • 1
  • Maryane Modolon Martins
    • 1
  • Andriele Vieira
    • 1
  • Sandra Bonfante
    • 1
  • Mariana Pereira Goldim
    • 1
  • Francieli Vuolo
    • 2
  1. 1.Clinical and Experimental Pathophysiology Laboratory—FICEXP, Graduate Program in Health SciencesUniversity of South Santa CatarinaTubarãoBrazil
  2. 2.Experimental Pathophysiology Laboratory—FISIOPAT, Graduate Program in Health SciencesUniversity of Southern of Santa CatarinaCriciumaBrazil

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