Skip to main content
SpringerLink
Log in

Attenuation of hyperglycemia-mediated oxidative stress by indole-3-carbinol and its metabolite 3, 3′- diindolylmethane in C57BL/6J mice

  • Original Paper
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

In this study, we have investigated the effect of the nutritive phytochemicals, indole-3-carbinol (I3C) and its metabolite, 3, 3′- diindolylmethane (DIM) on oxidative stress developed in type 2 diabetes mellitus (T2DM). This work was carried out in the genetically modified mouse (C57BL/6J mice) that closely simulated the metabolic abnormalities of the human disease after the administration of high fat diet (HFD). Glucose, insulin, hemoglobin (Hb), glycated hemoglobin (HbA1c), thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), conjugated dienes (CD), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), vitamin C, vitamin E, and reduced glutathione (GSH) levels were monitored in all the groups. Treatments positively modulate the glucose, insulin, and Hb and HbA1c levels in HFD mice. TBARS, LOOH, and CD were decreased in treatment groups when compared to the HFD group. Treatments increase SOD, CAT, GPx levels (erythrocyte, liver, kidney, and heart) and vitamin C, vitamin E, and GSH levels (plasma, liver, kidney, and heart) in diabetic mice. From the study, it was clear that the antioxidant-scavenging action were accelerated in mice treated with DIM than the I3C treatment group which was comparable with the standard drug metformin.

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

Similar content being viewed by others

References

  1. Aggarwal BB, Ichikawa H (2005) Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle 4:1201–1215

    Article  CAS  PubMed  Google Scholar 

  2. Arnao MB, Sanchez-Bravo J, Acosta M (1996) Indole-3-carbinol as a scavenger of free radicals. Biochem Mol Biol Int 39:1125–1134

    CAS  PubMed  Google Scholar 

  3. Baker H, Frank O, De Angelis B, Feingold S (1980) Plasma tocopherol in man at various times after ingesting free or acetylated tocopherol. Nutr Res 21:531–536

    CAS  Google Scholar 

  4. Biesalski HK, Vadivel V (2011) Contribution of phenolic compounds to the antioxidant potential and type II diabetes related enzyme inhibition properties of Pongamia pinnata L. Pierre seeds. Process Biochem 46:1973–1980

    Article  Google Scholar 

  5. Blum J, Fridovich I (1985) Inactivation of glutathione peroxidase by superoxide dismutase radical. Arch Biochem Biophys 240:500–508

    Article  CAS  PubMed  Google Scholar 

  6. Bonnefont-Rousselot D, Raji B, Walrand S, Gardes-Albert M, Jore D, Legrand A (2003) An intracellular modulation of free radical production could contribute to the beneficial effects of metformin towards oxidative stress. Metabolism 52:586–589

    Article  CAS  PubMed  Google Scholar 

  7. Burgi W, Briner M, Franken N, Kessler ACH (1988) One step sandwich enzyme immunoassay for insulin using monoclonal antibodies. Clin Biochem 21:311–314

    Article  CAS  PubMed  Google Scholar 

  8. Butterfeild JD, Mc Graw CP (1978) Free radical pathology. Stroke 9:443

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  10. Chang HP, Wang ML, Hsu CY, Liu ME, Chan MH, Chen YH (2011) Suppression of inflammation-associated factors by indole-3-carbinol in mice fed high-fat diets and in isolated, co-cultured macrophages and adipocytes. Int J Obes 3:1530–1538

    Article  Google Scholar 

  11. Chanwitheesuk A, Teerawutgulrag N, Rakariyatham (2005) Screening of antioxidant activity and antioxidant compounds of some edible plants of Thailand. Food Chem 92:491–497

    Article  CAS  Google Scholar 

  12. De Kruif CA, Marsman JW, Venekamp JC, Falke HE, Noordhoek J, Blaauboer BJ, Wortelboer HM (1991) Structure elucidation of acid reaction products of indole-3-carbinol: detection in vivo and enzyme induction in vitro. Chem Biol Interact 80:303–315

    Article  PubMed  Google Scholar 

  13. Drabkin DL, Austin JM (1932) Spectrophotometric constants for common haemoglobin derivatives in human, dog and rabbit blood. J Biol Chem 98:719–733

    CAS  Google Scholar 

  14. Dunn SE, Leblanc GA (1994) Hypocholesterolemic properties of plant indoles: inhibition of acyl-coa: cholesterol acyltransferase activity and reduction of serum LDL/VLDL cholesterol levels by glucobrassicin derivatives. Biochem Pharmacol 41:359–364

    Article  Google Scholar 

  15. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  PubMed  Google Scholar 

  16. Evans JL, Goldfine ID, Maddux BA, Grodsky GM (2002) Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 23:599–622

    Article  CAS  PubMed  Google Scholar 

  17. Geoffrey KM, Joan EK, Adele C, Andre GT (2007) Cruciferous indole-3-carbinol inhibits apolipoprotein B secretion in HepG2 cells1–3. J Nutr 137:2185–2189

    Google Scholar 

  18. Gregus Z, Fekete T, Halaszi E, Klaassen CD (1996) Lipoic acid impairs glycine conjugation of benzoic acid and renal excretion of benzoylglycine. Drug Metab Dispos 24:682–688

    CAS  PubMed  Google Scholar 

  19. Habig WH, Pabst MJ, Jakoby WBC (1974) Glutathione-S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    CAS  PubMed  Google Scholar 

  20. Jiang ZY, Hunt JV, Wolff SP (1992) Ferrous ion oxidation in the presence of xylenol orange for the detection of lipid hydroperoxides in low density lipoprotein. Anal Biochem 202:384–389

    Article  CAS  PubMed  Google Scholar 

  21. Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 21:130–132

    CAS  PubMed  Google Scholar 

  22. Kesavulu MM, Giri R, Kameswara Rao B, Apparao C (2000) Lipid peroxidation and antioxidant enzyme levels in type 2 diabetics with microvascular complications. Diabetes Metab 26:387–392

    CAS  PubMed  Google Scholar 

  23. Kim HW, Kim J, Kim J, Lee S, Choi BR, Han JS, Lee KW, Lee HJ (2014) 3,3′Diindolylmethane inhibits lipopolysaccharide-induced microglial hyperactivation and attenuates brain inflammation. Toxicol Sci 137:158–167

    Article  CAS  PubMed  Google Scholar 

  24. Kim YS, Milner JA (2005) Targets for indole-3-carbinol in cancer prevention. J Nutr Biochem 16:65–73

    Article  CAS  PubMed  Google Scholar 

  25. Lampe JW (1999) Health effects of vegetables and fruit: assessing mechanisms of action in human experimental studies. Am J Clin Nutr 70:475–490

    Google Scholar 

  26. Li W, Zhang M, Gu J, Meng ZJ, Zhao LC, Zheng YN, Chen L, Yang GL (2012) Hypoglycemic effect of protopanaxadiol-type ginsenosides and compound K on type 2 diabetes mice induced by high-fat diet combining with streptozotocin via suppression of hepatic gluconeogenesis. Fitoterapia 83:192–198

    Article  CAS  PubMed  Google Scholar 

  27. Lowry OH, Roseborough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin’s phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  28. Mark JA, Margaret MM, Richard V, Andreas G, William PS, Marion LW, Donald EM (2004) Physiological modeling of formulated and crystalline 3,3-diindolylmethane pharmacokinetics following oral administration in mice. Drug Metab Dispos 32:632–638

    Article  Google Scholar 

  29. Niehaus WG, Samuelsson B (1968) Formation of malondialdehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 6:126–130

    Article  CAS  PubMed  Google Scholar 

  30. Niskanen LK, Salonen JT, Nyssonen K, Uusitupa MIJ (1995) Plasma lipid peroxidation and hyperglycemia: a connection through hyperinsulinaemia? Diabet Med 12:802–808

    Article  CAS  PubMed  Google Scholar 

  31. Rao KS, Recknagel RO (1968) Early onset of lipoperoxidation in rat liver after carbon tetrachloride administration. Exp Mol Pathol 9:271–278

    Article  CAS  PubMed  Google Scholar 

  32. Roe JH, Kuether CA (1943) The determination of ascorbic acid in whole blood and urine through the 2, 4-dinitrophenylhydrazine derivative of dehydroascorbic acid. J Biol Chem 11:145–164

    Google Scholar 

  33. Rogan EG (2006) The natural chemopreventive compound indole-3-carbinol: state of the science. In Vivo 20:221–228

    CAS  PubMed  Google Scholar 

  34. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590

    Article  CAS  PubMed  Google Scholar 

  35. Sepkovic DW, Bradlow HL, Bell M (2001) Quantitative determination of 3,3 -diindolylmethane in urine of individuals receiving indole-3-carbinol. Nutr Cancer 41:57–63

    Article  CAS  PubMed  Google Scholar 

  36. Sharpe PC, Liu W-H, Yue KK, McMaster D, Catherwood MA, McGinty AM, Trimble ER (1998) Glucose induced oxidative stress in vascular contractile cells. Diabetes 47:801–809

    Article  CAS  PubMed  Google Scholar 

  37. Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394

    Article  CAS  PubMed  Google Scholar 

  38. Staub RE, Feng C, Onisko B, Bailey GS, Firestone GL, Bjeldanes LF (2002) Fate of indole-3-carbinol in cultured human breast tumor cells. Chem Res Toxicol 15:101–109

    Article  CAS  PubMed  Google Scholar 

  39. Sudhakar NS, Pattabiraman TN (1981) A new colorimetric method for the estimation of glycosylated haemoglobin. Clin Chim Acta 109:267–274

    Article  Google Scholar 

  40. Sundaresan A, Pugalendi KV (2012) Combined effect of ursolic acid and rosiglitazone on redox status in high fat diet induced C57BL/6J mice. J Pharm Res 5:2380–2384

    Google Scholar 

  41. Weng J-R, Tsai C-H, Kulp SK, Che C-S (2008) Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer Lett 262:153–163

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Zimmet P (2003) The burden of type 2 diabetes: are we doing enough? Diabetes Metab 29:9–18

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608002, Tamilnadu, India

    Poornima Jayakumar, Kodukkur Vishwanath Pugalendi & Mirunalini Sankaran

Authors
  1. Poornima Jayakumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kodukkur Vishwanath Pugalendi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mirunalini Sankaran
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mirunalini Sankaran.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jayakumar, P., Pugalendi, K.V. & Sankaran, M. Attenuation of hyperglycemia-mediated oxidative stress by indole-3-carbinol and its metabolite 3, 3′- diindolylmethane in C57BL/6J mice. J Physiol Biochem 70, 525–534 (2014). https://doi.org/10.1007/s13105-014-0332-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-014-0332-5

Keywords

Search

Navigation