Skip to main content
SpringerLink
Log in

Oxidative stress parameters in blood, liver, and kidney of diabetic rats treated with curcumin and/or insulin

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

This study evaluated the effects of curcumin and/or insulin on antioxidant enzyme activity in blood, liver, and kidney, as well as on lipid peroxidation and delta aminolevulinic dehydratase (δ-ALA-D) activity, and a histopathological analysis of streptozotocin-induced diabetic rats. The animals were divided into six groups (n = 6): control/saline (C); control/curcumin (CCur); diabetic/saline (D); diabetic/insulin (DIns); diabetic/curcumin (DCur); and diabetic/insulin/curcumin (DInsCur). After 30 days of treatment with curcumin and/or insulin, the animals were sacrificed and the liver, kidney, and serum were used for experimental determinations. Results of histopathological analysis showed that the treatment with insulin ameliorate renal and hepatic lesions from both DIns and DInsCur groups. TBARS levels were significantly increased in serum, liver, and kidney in D group and the administration of curcumin and insulin prevented this increase in DIns and DCur groups. The activities of catalase (CAT), superoxide dismutase, and δ-ALA-D presented a significant decrease in the liver and kidney D group when compared to C group (P < 0.05). The animals treated with curcumin and insulin presented an increase of CAT activity, revealing a positive interaction between both substances. The treatments with curcumin or insulin prevented oxidative stress in blood, through modulation of enzymatic antioxidant defenses. These findings contributed to the comprehension that antioxidants from medicinal plants could be used as adjuvant in the treatment of this endocrinopathy and not as single therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Rahimi R, Nikfar S, Larijani B, Abdollahi M (2005) A review on the role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother 59:365–373

    Article  CAS  PubMed  Google Scholar 

  2. Robertson RP (2004) Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. J Biol Chem 279:42351–42354

    Article  CAS  PubMed  Google Scholar 

  3. Maritim AC, Sanders RA, Watkins JB 3rd (2003) Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 17:24–38

    Article  CAS  PubMed  Google Scholar 

  4. Wu KK and Huan Y (2008) Streptozotocin-induced diabetic models in mice and rats. Curr Protoc Pharmacol Chap 5, Unit 5. 47

  5. Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820

    Article  CAS  PubMed  Google Scholar 

  6. Ceriello A (2000) Oxidative stress and glycemic regulation. Metabolism 49:27–29

    Article  CAS  PubMed  Google Scholar 

  7. Maiese K, Morhan SD, Chong ZZ (2007) Oxidative stress biology and cell injury during type 1 and type 2 diabetes mellitus. Curr Neurovasc Res 4:63–71

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Daneman D (2006) Type 1 diabetes. Lancet 367:847–858

    Article  CAS  PubMed  Google Scholar 

  9. Osawa T, Kato Y (2005) Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia. Ann N Y Acad Sci 1043:440–451

    Article  CAS  PubMed  Google Scholar 

  10. Fernandez-Cuartero B, Rebollar JL, Batlle A, Enriquez de Salamanca R (1999) Delta aminolevulinate dehydratase (ALA-D) activity in human and experimental diabetes mellitus. Int J Biochem Cell Biol 31:479–488

    Article  CAS  PubMed  Google Scholar 

  11. Folmer V, Soares JC, Gabriel D, Rocha JB (2003) A high fat diet inhibits delta-aminolevulinate dehydratase and increases lipid peroxidation in mice (Mus musculus). J Nutr 133:2165–2170

    CAS  PubMed  Google Scholar 

  12. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247

    Article  CAS  PubMed  Google Scholar 

  13. Murugan P, Pari L (2007) Influence of tetrahydrocurcumin on erythrocyte membrane bound enzymes and antioxidant status in experimental type 2 diabetic rats. J Ethnopharmacol 113:479–486

    Article  CAS  PubMed  Google Scholar 

  14. Hassaninasab A, Hashimoto Y, Tomita-Yokotani K, Kobayashi M (2011) Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism. Proc Natl Acad Sci USA 108:6615–6620

    Article  CAS  PubMed  Google Scholar 

  15. Kuhad A, Chopra K (2007) Curcumin attenuates diabetic encephalopathy in rats: behavioral and biochemical evidences. Eur J Pharmacol 576:34–42

    Article  CAS  PubMed  Google Scholar 

  16. Jentzsch AM, Bachmann H, Furst P, Biesalski HK (1996) Improved analysis of malondialdehyde in human body fluids. Free Radic Biol Med 20:251–256

    Article  CAS  PubMed  Google Scholar 

  17. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  18. Nelson DP, Kiesow LA (1972) Enthalpy of decomposition of hydrogen peroxide by catalase at 25 degrees C (with molar extinction coefficients of H2O2 solutions in the UV). Anal Biochem 49:474–478

    Article  CAS  PubMed  Google Scholar 

  19. Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247:3170–3175

    CAS  PubMed  Google Scholar 

  20. McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244:6049–6055

    CAS  PubMed  Google Scholar 

  21. Sassa S (1982) Delta-aminolevulinic acid dehydratase assay. Enzyme 28:133–145

    CAS  PubMed  Google Scholar 

  22. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  23. Hatcher H, Planalp R, Cho J, Torti FM, Torti SV (2008) Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci 65:1631–1652

    Article  CAS  PubMed  Google Scholar 

  24. Babu PS, Srinivasan K (1995) Influence of dietary curcumin and cholesterol on the progression of experimentally induced diabetes in albino rat. Mol Cell Biochem 152:13–21

    CAS  PubMed  Google Scholar 

  25. DeWitt DE, Hirsch IB (2003) Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. JAMA 289:2254–2264

    Article  CAS  PubMed  Google Scholar 

  26. Harris EH (2005) Elevated liver function tests in type 2 diabetes. Clin Diabetes 23:115–119

    Article  Google Scholar 

  27. Schmatz R, Perreira LB, Stefanello N, Mazzanti C, Spanevello R, Gutierres J, Bagatini M, Martins CC, Abdalla FH, da Silva Daci, Serres J, Zanini D, Vieira JM, Cardoso AM, Schetinger MR, Morsch VM (2012) Effects of resveratrol on biomarkers of oxidative stress and on the activity of delta aminolevulinic acid dehydratase in liver and kidney of streptozotocin-induced diabetic rats. Biochimie 94:374–383

    Article  CAS  PubMed  Google Scholar 

  28. Jeschke MG, Rensing H, Klein D, Schubert T, Mautes AE, Bolder U, Croner RS (2005) Insulin prevents liver damage and preserves liver function in lipopolysaccharide-induced endotoxemic rats. J Hepatol 42:870–879

    Article  CAS  PubMed  Google Scholar 

  29. Hamden K, Boujbiha MA, Masmoudi H, Ayadi FM, Jamoussi K, Elfeki A (2009) Combined vitamins (C and E) and insulin improve oxidative stress and pancreatic and hepatic injury in alloxan diabetic rats. Biomed Pharmacother 63:95–99

    Article  CAS  PubMed  Google Scholar 

  30. Caballero F, Gerez E, Batlle A, Vazquez E (2000) Preventive aspirin treatment of streptozotocin induced diabetes: blockage of oxidative status and revertion of heme enzymes inhibition. Chem Biol Interact 126:215–225

    Article  CAS  PubMed  Google Scholar 

  31. Stark G (2005) Functional consequences of oxidative membrane damage. J Membr Biol 205:1–16

    Article  CAS  PubMed  Google Scholar 

  32. Santini SA, Marra G, Giardina B, Cotroneo P, Mordente A, Martorana GE, Manto A, Ghirlanda G (1997) Defective plasma antioxidant defenses and enhanced susceptibility to lipid peroxidation in uncomplicated IDDM. Diabetes 46:1853–1858

    Article  CAS  PubMed  Google Scholar 

  33. Gate L, Paul J, Ba GN, Tew KD, Tapiero H (1999) Oxidative stress induced in pathologies: the role of antioxidants. Biomed Pharmacother 53:169–180

    Article  CAS  PubMed  Google Scholar 

  34. Callahan HL, Crouch RK, James ER (1988) Helminth anti-oxidant enzymes: A protective mechanism against host oxidants? Parasitol Today 4:218–225

    Article  CAS  PubMed  Google Scholar 

  35. Turk HM, Sevinc A, Camci C, Cigli A, Buyukberber S, Savli H, Bayraktar N (2002) Plasma lipid peroxidation products and antioxidant enzyme activities in patients with type 2 diabetes mellitus. Acta Diabetol 39:117–122

    Article  CAS  PubMed  Google Scholar 

  36. Sharma S, Kulkarni SK, Chopra K (2006) Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats. Clin Exp Pharmacol Physiol 33:940–945

    Article  CAS  PubMed  Google Scholar 

  37. Aggarwal BB, Harikumar KB (2009) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 41:40–59

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Gupta SC, Prasad S, Kim JH, Patchva S, Webb LJ, Priyadarsini IK, Aggarwal BB (2011) Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep 28:1937–1955

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Han X, Xu B, Beevers CS, Odaka Y, Chen L, Liu L, Luo Y, Zhou H, Chen W, Shen T, Huang S (2012) Curcumin inhibits protein phosphatases 2A and 5, leading to activation of mitogen-activated protein kinases and death in tumor cells. Carcinogenesis 33:868–875

    Article  CAS  PubMed  Google Scholar 

  40. Chen L, Xu B, Liu L, Luo Y, Yin J, Zhou H, Chen W, Shen T, Han X, Huang S (2010) Hydrogen peroxide inhibits mTOR signaling by activation of AMPKalpha leading to apoptosis of neuronal cells. Lab Invest 90:762–773

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Wiernsperger NF (2003) Oxidative stress as a therapeutic target in diabetes: revisiting the controversy. Diabetes Metab 29:579–585

    Article  CAS  PubMed  Google Scholar 

  42. Kade IJ, Borges VC, Savegnago L, Ibukun EO, Zeni G, Nogueira CW, Rocha JB (2009) Effect of oral administration of diphenyl diselenide on antioxidant status, and activity of delta aminolevulinic acid dehydratase and isoforms of lactate dehydrogenase, in streptozotocin-induced diabetic rats. Cell Biol Toxicol 25:415–424

    Article  CAS  PubMed  Google Scholar 

  43. Brito VB, Folmer V, Soares JC, Silveira ID, Rocha JB (2007) Long-term sucrose and glucose consumption decreases the delta-aminolevulinate dehydratase activity in mice. Nutrition 23:818–826

    Article  CAS  PubMed  Google Scholar 

  44. Souza JB, Rocha JB, Nogueira CW, Borges VC, Kaizer RR, Morsch VM, Dressler VL, Martins AF, Flores EM, Schetinger MR (2007) Delta-aminolevulinate dehydratase (delta-ALA-D) activity in diabetes and hypothyroidism. Clin Biochem 40:321–325

    Article  CAS  PubMed  Google Scholar 

  45. Garro JC, Polo CF, Cirigliano A, Rossetti MV, Wider EA (1990) Glucose effect on haem metabolism. Mol Aspects Med 11:28

    Google Scholar 

Download references

Acknowledgments

We thank Brazilian Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – CAPES for supported this work.

Ethical approval

The procedure was approved by the Animal Welfare Committee of UFSM, number 018/2012, in accordance to Brazilian laws and ethical principles published by the Colégio Brasileiro de Experimentação Animal (COBEA).

Author information

Authors and Affiliations

  1. Department of Small Animals, Hospital Veterinário, Universidade Federal de Santa Maria, Faixa de Camobi, Km 9, Avenida Roraima no 1000, Campus Universitário, Sala 103, Santa Maria, RS, 97105-900, Brazil

    Heloisa Einloft Palma, Marcos M. B. Corrêa, Verônica S. P. Castro, Andréia B. Pereira, Andressa Bueno, Debora Rosolen, Thaís R. Mann, Bianca S. de Cecco, Sonia T. A. Lopes & Cinthia M. A. Mazzanti

  2. Department of Chemistry, Universidade Federal de Santa Maria, Faixa de Camobi, Km 9, Avenida Roraima no 1000, Campus Universitário, Prédio 18, Santa Maria, RS, 97105-900, Brazil

    Patrícia Wolkmer, Roberta Schmatz, Gustavo R. Thomé, Luciane B. Pereira & Lizielle S. de Oliveira

  3. Department of Large Animals, Hospital Veterinário, Universidade Federal de Santa Maria, Faixa de Camobi, Km 9, Avenida Roraima no 1000, Campus Universitário, Sala 103, Santa Maria, RS, 97105-900, Brazil

    Miguel Gallio

  4. Department of Pathology, Universidade Federal de Santa Maria, Faixa de Camobi, Km 9, Avenida Roraima no 1000, Campus Universitário, Hospital Veterinário, Santa Maria, RS, 97105-900, Brazil

    Dominguita L. Graça

Authors
  1. Heloisa Einloft Palma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrícia Wolkmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miguel Gallio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marcos M. B. Corrêa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roberta Schmatz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gustavo R. Thomé
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Luciane B. Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Verônica S. P. Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andréia B. Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Andressa Bueno
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Lizielle S. de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Debora Rosolen
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Thaís R. Mann
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Bianca S. de Cecco
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Dominguita L. Graça
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Sonia T. A. Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Cinthia M. A. Mazzanti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Heloisa Einloft Palma or Cinthia M. A. Mazzanti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Palma, H.E., Wolkmer, P., Gallio, M. et al. Oxidative stress parameters in blood, liver, and kidney of diabetic rats treated with curcumin and/or insulin. Mol Cell Biochem 386, 199–210 (2014). https://doi.org/10.1007/s11010-013-1858-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1858-5

Keywords

Search

Navigation