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Protective effects of azelaic acid against high-fat diet-induced oxidative stress in liver, kidney and heart of C57BL/6J mice

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Abstract

Excess fat intake induces hyperinsulinaemia, increases nutrient uptake and lipid accumulation, amplifies ROS generation, establishes oxidative stress and morphological changes leading to tissue injury in the liver, kidney and heart of high-fat diet (HFD)-fed mice. The effect of azelaic acid (AzA), a C9 α,ω-dicarboxylic acid, against HFD-induced oxidative stress was investigated by assaying the activities and levels of antioxidants and oxidative stress markers in the liver, kidney and heart of C57BL/6J mice. Mice were segregated into two groups, one fed standard diet (NC) and the other fed high-fat diet (HFD) for 15 weeks. HFD-fed mice were subjected to intragastric administration of AzA (80 mg/kg BW)/RSG (10 mg/kg BW) during 11-15 weeks. Glucose, insulin, triglycerides, hepatic and nephritic markers were analysed in the plasma and the activity of enzymatic, non-enzymatic antioxidants and lipid peroxidation markers were examined in the plasma/erythrocytes, liver, kidney and heart of normal and experimental mice. We inferred significant decrease in enzymatic and non-enzymatic antioxidants along with significant increase in glucose, insulin, hepatic and nephritic markers, triglycerides and lipid peroxidation markers in HFD-fed mice. Administration of AzA could positively restore the levels of plasma glucose, insulin, triglycerides, hepatic and nephritic markers to near normal. AzA increased the levels of enzymatic and nonenzymatic antioxidants with significant reduction in the levels of lipid peroxidation markers. Histopathological examination of liver, kidney and heart substantiated these results. Hence, we put forward that AzA could counteract the potential injurious effects of HFD-induced oxidative stress in C57BL/6J mice.

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References

  1. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Nakajima Y, Nakayama O (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Investig 114:1752–1761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Buettner R, Scholmerich J, Bollheimer LC (2007) High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity 15:798–808

    Article  CAS  PubMed  Google Scholar 

  3. Mathur A, Marine M, Lu D, Swartz-Basile DA, Saxena R, Zyromski NJ, Pitt HA (2007) Nonalcoholic fatty pancreas disease. HPB (Oxford) 9:312–318

    Article  Google Scholar 

  4. Matsuzawa-Nagata N, Takamura T, Ando H, Nakamura S, Kurita S, Misu H (2008) Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity. Met Clin Exp 57:1071–1077

    Article  CAS  Google Scholar 

  5. Reaven G, Abbasi F, McLaughlin T (2004) Obesity, insulin resistance, and cardiovascular disease. Recent Prog Horm Res 59:207–223

    Article  CAS  PubMed  Google Scholar 

  6. Mohanty P, Ghanim H, Hamouda W, Aljada A, Garg R, Dandona P (2002) Both lipid and protein intakes stimulate increased generation of reactive oxygen species by polymorphonuclear leukocytes and mononuclear cells. Am J Clin Nutr 75:767–772

    CAS  PubMed  Google Scholar 

  7. Olusi SO (2002) Obesity is an independent risk factor for plasma lipid peroxidation and depletion of erythrocyte cytoprotecticve enzymes in humans. Int J Obes 26:1159–1164

    Article  CAS  Google Scholar 

  8. Fraulob JC, Diamantino RO, Fernandes-Santos C, Aguila MB, Mandarim-de-Lacerda CA (2010) A mouse model of metabolic syndrome: insulin resistance, fatty liver and non-alcoholic fatty pancreas disease (NAFPD) in C57BL/6 mice fed a high fat diet. J Clin Biochem Nutr 46:212–223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nissen SE, Wolski K (2010) Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med 26:1191–1201

    Google Scholar 

  10. Home PD, Pocock SJ, Beck-Nielsen H, Curtis PS, Gomis R, Hanefeld M, Jones NP, Komajda M, McMurray JJ (2009) Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, openlabel trial. Lancet 373:2125–2135

    Article  CAS  PubMed  Google Scholar 

  11. Anderson JW, Hanna TJ, Peng X, Kryscio RJ (2000) Whole grain foods and heart disease risk. J Am Coll Nutr 19:291S–299S

    Article  CAS  PubMed  Google Scholar 

  12. Montonen J, Knekt P, Jarvinen R, Aromaa A, Reunanen A (2007) Whole-grain and fiber intake and the incidence of type 2 diabetes. Am J Clin Nutr 77:622–629

    Google Scholar 

  13. Munter JS, Hu FB, Spiegelman D, Franz M, Dam RMV (2007) Whole grain, bran and germ intake and risk of type 2 diabetes: a prospective cohort study and systematic review. PLoS Med 4:e261

    Article  PubMed  PubMed Central  Google Scholar 

  14. Mehmood S, Orhan I, Ahsan Z, Aslan S, Gulfraz M (2008) Fatty acid composition of seed oil of different Sorghum bicolor varieties. Food Chem 109:855–859

    Article  CAS  PubMed  Google Scholar 

  15. Marsden JR, Shuster S (1983) The effect of azelaic acid on acne. Br J Dermatol 109:723–725

    Article  CAS  PubMed  Google Scholar 

  16. Breathnach AS (1999) Azelaic acid: potential as a general antitumoural agent. Med Hypotheses 52:221–226

    Article  CAS  PubMed  Google Scholar 

  17. Charnock C, Brudeli B, Klaveness J (2004) Evaluation of the antibacterial efficacy of diesters of azelaic acid. Eur J Pharm Sci 21:589–596

    Article  CAS  PubMed  Google Scholar 

  18. Nguyen QH, Bui TP (1995) Azelaic acid: pharmacokinetic and pharmacodynamic properties and its therapeutic role in hyperpigmentary disorders and acne. Int J Dermatol 34:75–84

    Article  CAS  PubMed  Google Scholar 

  19. Mastrofrancesco A, Ottaviani M, Aspite N (2010) Azelaic acid modulates the inflammatory response in normal human keratinocytes through PPAR gamma activation. Exp Dermatol 19:813–820

    Article  CAS  PubMed  Google Scholar 

  20. Trinder P (1969) Determination of blood glucose using an oxidase peroxidase system with a non carcinogenic chromogen. J Clin Pathol 22:158–161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Burgi W, Briner M, Franken N, Kessler ACH (1998) One step sandwich enzyme immunoassay for insulin using monoclonal antibodies. Clin Biochem 213:11–314

    Google Scholar 

  22. Reitman S, Frankel S (1957) A colorimetric method for the determination of serum glutamate oxaloacetic and glutamate pyruvic transaminases. Am J Clin Pathol 28:56–63

    Article  CAS  PubMed  Google Scholar 

  23. Kind PR, King EJ (1954) Estimation of plasma phosphatase by determination of hydrolyzed phenol with amino-antipyrine. J Clin Pathol 7:322–326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Fawcett JK, Scott JE (1960) A rapid and precise method for the determination of urea. J Clin Path 3:156–159

    Article  Google Scholar 

  25. Caraway WT (1955) Determination of uric acid in serum by carbonate method. Am J Clin Path 25:840–845

    CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  29. Habig WH, Pabst MJ, Jakoby WBC (1974) Glutathione-S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249(22):7130–7139

    CAS  PubMed  Google Scholar 

  30. Pinto RE, Bartley W (1969) The effect of age and sex on glutathione reductase and glutathione peroxidase activities on aerobic glutathione oxidation in rat liver homogenate. Biochem J 12:109–115

    Article  Google Scholar 

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

    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. Baker H, Frank O, DeAngelis 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 

  34. 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 

  35. 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 

  36. Surwit RS, Feinglos MN, Rodin J (1995) Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice. Metabolism 44:645–651

    Article  CAS  PubMed  Google Scholar 

  37. Mei J, Yu S, Ahren B (2010) Study on administration of 1,5-anhydro-d-fructose in C57BL/6J mice challenged with high-fat diet. BMC Endocr Disord 10(17):1–5

    CAS  Google Scholar 

  38. Kim MR, Park Y, Albright KJ, Pariza MW (2002) Differential responses of hamsters and rats fed high-fat or low-fat diets supplemented with conjugated linoleic acid. Nutr Res 22:715–722

    Article  CAS  Google Scholar 

  39. Gallou-Kabani Vige A, Gross MS (2007) C57BL/6J and A/J mice fed a high fat diet delineate components of metabolic syndrome. Obesity 15:1996–2005

    Article  CAS  PubMed  Google Scholar 

  40. Vozarova B, Stefan N, Lindsay RS, Saremi A, Pratley RA, Bogardus C et al (2002) High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. Diabetes 51:1889–1895

    Article  CAS  PubMed  Google Scholar 

  41. Myers VC, Fine MS (1918) Comparative distribution of urea, creatinine, uric acid and sugar in the blood and spinal fluid. Am J Med Sci 76:239–244

    Google Scholar 

  42. Moron MS, Dipierre JW, Mannervik B (1979) Levels of glutathione reductase and glutathione-S-transferase activities in rat lung and liver. Biochim Biophys Acta 582(1):67–68

    Article  CAS  PubMed  Google Scholar 

  43. Halliwell B, Gutteridge JMC (1990) Role of free radicals and catalytic metal ions in human disease. Methods Enzymol 186:1–85

    Article  CAS  PubMed  Google Scholar 

  44. Ingold KU, Webb AC, Witter D, Burton GW, Metcalf TA, Muller DP (1987) Vitamin E remains the major lipid soluble, chain breaking antioxidant in human plasma even in individuals suffering from severe vitamin E deficiency. Arch Biochem Biophys 259(1):224–225

    Article  CAS  PubMed  Google Scholar 

  45. Packer L, Tritschler HJ, Wessel K (1997) Neuroprotection by metabolic antioxidant alpha lipoic acid. Free Radic Biol Med 22(1–2):359–378

    Article  CAS  PubMed  Google Scholar 

  46. Freisleben HJ, Packer L (1993) Free-radical scavenging activities, interactions and recycling of antioxidants. Biochem Soc Trans 21(2):325–330

    Article  CAS  PubMed  Google Scholar 

  47. Hayes JD, Flanagan JU, Jowsey IR (2005) Glutathione transferases. Annu Rev Pharmacol Toxicol 45:51–88

    Article  CAS  PubMed  Google Scholar 

  48. Cathcart RF (1985) Vitamin C: the nontoxic, nonrate-limited, antioxidant free radical scavenger. Med Hypotheses 18(1):61–77

    Article  CAS  PubMed  Google Scholar 

  49. Godin DV, Wohaieb SA, Garnett ME, Goumeniouk AD (1988) Antioxidant enzyme alterations in experimental and clinical diabetes. Mol Cell Biochem 84:223–231

    Article  CAS  PubMed  Google Scholar 

  50. Baynes JW (1991) Perspectives in diabetes: role of oxidative stress in development of complications in diabetes. Diabetes 40:405–412

    Article  CAS  PubMed  Google Scholar 

  51. Rizvi SI, Maurya PK (2007) Markers of oxidative stress in erythrocytes during aging in humans. Ann N Y Acad Sci 1100:373–382

    Article  CAS  PubMed  Google Scholar 

  52. Haggai MC, Nieto N (2005) A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. FASEB J 19:136–138

    Google Scholar 

  53. Agarwal R, Vasavada N, Sachs NG, Chase S (2004) Oxidative stress and renal injury with intravenous iron in patients with chronic kidney disease. Kidney Int 65:2279–2289

    Article  CAS  PubMed  Google Scholar 

  54. Kume S, Uzu T, Araki S, Sugimoto T, Isshiki K, Kanasaki M (2007) Role of altered renal lipid metabolism in the development of renal injury induced by a high-fat diet. J Am Soc Nephrol 18:2715–2723

    Article  CAS  PubMed  Google Scholar 

  55. Bournoville ML, Conti M, Bazin R, Michel O, Bariéty J, Chevalier J (1999) Oxidative stress occurs in absence of hyperglycaemia and inflammation in the onset of kidney lesions in normotensive obese rats. Nephrol Dial Transpl 15(4):467–476

    Google Scholar 

  56. Vincent HK, Powers SK, Dirks AJ, Scarpace P (2001) Mechanism for obesity induced increase in myocardial lipid peroxidation. Int J Obes 25:378–388

    Article  CAS  Google Scholar 

  57. Esterbauer H, Gebicki J, Puhl H, Jurgens G (1992) The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radical Biol Med 13:341–390

    Article  CAS  Google Scholar 

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Acknowledgments

The author(s) sincerely thank Indian Council of Medical Research, India for providing financial support for this research project, in the form of Senior Research Fellowship (ICMR-SRF), to Mrs. Shanmugam Muthulakshmi.

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The authors declared no conflict of interest.

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  1. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar, 608 002, Tamil Nadu, India

    Shanmugam Muthulakshmi & Ramalingam Saravanan

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  1. Shanmugam Muthulakshmi
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  2. Ramalingam Saravanan
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Correspondence to Ramalingam Saravanan.

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Muthulakshmi, S., Saravanan, R. Protective effects of azelaic acid against high-fat diet-induced oxidative stress in liver, kidney and heart of C57BL/6J mice. Mol Cell Biochem 377, 23–33 (2013). https://doi.org/10.1007/s11010-013-1566-1

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