Skip to main content
Log in

Dietary Flaxseed Oil Supplementation Mitigates the Effect of Lead on the Enzymes of Carbohydrate Metabolism, Brush Border Membrane, and Oxidative Stress in Rat Kidney Tissues

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Lead is a heavy metal widely distributed in the environment. Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic illnesses. Human and animal exposure demonstrates that lead is nephrotoxic. However, attempts to reduce lead-induced nephrotoxicity were not found suitable for clinical use. Recently, flaxseed oil (FXO), a rich source of ω-3 fatty acids and lignans, has been shown to prevent/reduce the progression of certain types of cardiovascular and renal disorders. In view of this, the present study investigates the protective effect of FXO on lead acetate (PbAc)-induced renal damage. Rats were pre-fed normal diet and the diet rich in FXO for 14 days, and then, four doses of lead acetate (25 mg/kg body weight) were administered intraperitoneally while still on diet. Various serum parameters, enzymes of carbohydrate metabolism, brush border membrane (BBM), and oxidative stress were analyzed in rat kidney. PbAc nephrotoxicity was characterized by increased serum creatinine and blood urea nitrogen. PbAc increased the activities of lactate dehydrogenase and NADP-malic enzyme, whereas it decreased malate and glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and BBM enzyme activities. PbAc caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation and decreased activities of superoxide dismutase, glutathione peroxidase, and catalase. In contrast, FXO alone enhanced the enzyme activities of carbohydrate metabolism, BBM, and antioxidant defense system. FXO feeding to PbAc-treated rats markedly enhanced resistance to PbAc-elicited deleterious effects. In conclusion, dietary FXO supplementation ameliorated PbAc-induced specific metabolic alterations and oxidative damage by empowering antioxidant defense mechanism and improving BBM integrity and energy metabolism.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Barbier O, Jacquillet G, Tauc M, Cougnan M, Poujeol P (2005) Effect of heavy metals on, and handling by kidney. Nephron Physiol 99:105–110

    Article  Google Scholar 

  2. Loghman-Adham M (1997) Renal effects of environmental and occupational lead exposure. Environ Health Perspect 105:928–939

    Article  PubMed  CAS  Google Scholar 

  3. Damek-Poprawa M, Sawicka-Kapusta K (2004) Histopathological changes in the liver, kidneys, and testes of bank voles environmentally exposed to heavy metal emissions from the steelworks and zinc smelter in Poland. Environ Res 96:72–78

    Article  PubMed  CAS  Google Scholar 

  4. Bressler J, Kim KA, Chakraborti T, Goldstein G (1999) Molecular mechanisms of lead neurotoxicity. Neurochem Res 24:595–600

    Article  PubMed  CAS  Google Scholar 

  5. Khalil-Manesh F, Gonick HC, Weiler EW, Prins B, Weber MA, Purdy RE (1993) Lead-induced hypertension: possible role of endothelial factors. Am J Hypertens 6:723–729

    PubMed  CAS  Google Scholar 

  6. Khalil-Manesh F, Gonick HC, Cohen AH (1992) Experimental model of lead nephropathy. I. Continuous high-dose lead injection. Kidney Int 41:1192–1203

    Article  PubMed  CAS  Google Scholar 

  7. Khalil-Manesh F, Gonick HC, Cohen A (1992) Experimental model of lead nephropathy. II. Effect of removal from lead exposure and chelation treatment with dimercaptosuccinic acid (DMSA). Environ Res 58:35–54

    Article  PubMed  CAS  Google Scholar 

  8. Fowler BA, Kimmel CA, Woods JS, Mc Connel EE, Grant LD (1980) Chronic low level lead toxicity in the rat: III. An integrated assessment of long term toxicity with special reference to the kidneys. Toxicol Appl Pharmacol 56:59–77

    Article  PubMed  CAS  Google Scholar 

  9. Goyer RA, Krall R (1969) Ultrastructural transformation in mitochondria isolated from kidneys of normal and lead-intoxicated rats. J Cell Biol 41:393–400

    Article  PubMed  CAS  Google Scholar 

  10. Goyer RA (1993) Lead toxicity: current concerns. Environ Health Perspect 100:177–187

    Article  PubMed  CAS  Google Scholar 

  11. Huguet JM, Braun JP, Burgat-Sacaze V, Bernard P, Rico AG (1982) Acute kidney disturbances by lead acetate in the rat. Toxicol Lett 10:395–398

    Article  PubMed  CAS  Google Scholar 

  12. Choie DD, Richter GW (1980) Effects of lead on the kidney. In: Singhal RL, Thomas JA (eds) Lead Toxicity. Urban and Schwarzenberg, Baltimore, pp 187–212

    Google Scholar 

  13. Abdel Moneim AE, DkhilMA A-QS (2011) The protective effect of flaxseed oil on lead acetate-induced renal toxicity in rats. J Hazard Mater 194:250–255

    Article  PubMed  CAS  Google Scholar 

  14. Hsu PC, Hsu CC, Liu MY, Chen LY, Guo YL (1998) Lead-induced changes in spermatozoa function and metabolism. Toxicology 55:45–64

    CAS  Google Scholar 

  15. Mishra M, Acharya UR (2004) Protective action of vitamins on the spermatogenesis in lead-treated Swiss mice. J Trace Elem Med Biol 18(2):173–178

    Article  PubMed  CAS  Google Scholar 

  16. Flora SJS, Mittal M, Mehta A (2008) Heavy metal induced oxidative stress and its possible reversal by chelation therapy. Indian J Med Res 128:501–523

    PubMed  CAS  Google Scholar 

  17. Nocentini S, Guggiari M, Rouillard D, Surgis S (2001) Exacerbating effect of vitamin E supplementation on DNA damage induced in cultured human normal fibroblasts by UVA radiation. Photochem Photobiol 73:370–377

    Article  PubMed  CAS  Google Scholar 

  18. Simopoulos AP (1999) Essential fatty acids in health and chronic disease. Am J Clin Nutr 70:560S–569S

    PubMed  CAS  Google Scholar 

  19. Lin X, Gingrich JR, Bao W, Li J, Haroon ZA, Demark-Wahnefried W (2002) Effect of flaxseed supplementation on prostatic carcinoma in transgenic mice. Urology 60:919–924

    Article  PubMed  Google Scholar 

  20. Newairy AS, Abdou HM (2009) Protective role of flax lignans against lead acetate induced oxidative damage and hyperlipidemia in rats. Food Chem Toxicol 47(4):813–818

    Article  PubMed  CAS  Google Scholar 

  21. Larsson S, Kumlin M, Ingelman-Sundberg M, Wolk A (2004) Dietary long chain n-3 fatty acids for the prevention of cancer. Am J Clin Nutr 79:935–945

    PubMed  CAS  Google Scholar 

  22. Williams DS, Verghese M, Walker LT, Boateng J, Shackelford LA, Guyton M, Jones J, Khatiwada J, Chawan CB (2008) Chemopreventive effects of flaxseed oil and flaxseed meal on azoxymethane-induced colon tumors in Fisher 344 Male rats. Int J Cancer 2:28–40

    Google Scholar 

  23. Sinclair AJ, Attar-Bashi NM, Li D (2000) What is the role of α-linolenic acid for mammals? Lipids 37:1113–1123

    Article  Google Scholar 

  24. Burdge GC, Calder PC (2005) Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults. Reprod Nutr Dev 45:581–589

    Article  PubMed  CAS  Google Scholar 

  25. Valsta LM, Salminen I, Aro A, Mutanen M (1996) Alpha-linolenic acid in rapeseed oil partly compensates for the effect of fish restriction on plasma long chain n-3 fatty acids. Eur J Clin Nutr 50:229–235

    PubMed  CAS  Google Scholar 

  26. Kitts D, Yuan Y, Wijewichreme A, Thompson L (1999) Antioxidant activity of the flaxseed lignan secoisoiciresnol diglycoside and its mammalian lignan metabolites enterodiol and enterolactone. Mol Cell Biochem 202:91–100

    Article  PubMed  CAS  Google Scholar 

  27. Abdel-Moneim AE, Dkhil MA, Al-Quraishy S (2010) The redox status in rats treated with flaxseed oil and lead-induced hepatotoxicity. Biol Trace Elem Res 143(1):457–467

    Article  PubMed  Google Scholar 

  28. Khundmiri SJ, Asghar M, Banday AA, Khan F, Salim S, Levi M, Yusufi ANK (2005) Effect of reperfusion on sodium dependent phosphate transport in renal brush border membranes. Biochim Biophys Acta 1716:19–28

    Article  PubMed  CAS  Google Scholar 

  29. Khundmiri SJ, Asghar M, Khan F, Salim S, Yusufi ANK (2004) Effect of ischemia and reperfusion on enzymes of carbohydrate metabolism in rat kidney. J Nephrol 17:1–7

    Google Scholar 

  30. Crane RK, Sols A (1953) The association of particulate fractions of brain and other tissue homogenates. J Biol Chem 203:273–292

    PubMed  CAS  Google Scholar 

  31. Nelson NA (1944) Photometric adaptation of the Somogyi method for the determination of glucose. J Biol Chem 153:375–381

    CAS  Google Scholar 

  32. Farooq N, Yusufi ANK, Mahmood R (2004) Effect of fasting on enzymes of carbohydrate metabolism and brush border membrane in rat intestine. Nutr Res 24:407–416

    Article  CAS  Google Scholar 

  33. Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autooxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474

    Article  PubMed  CAS  Google Scholar 

  34. Giri U, Iqbal M, Athar M (1996) Porphyrin mediated photosensitization has a weak tumor promoting activity in mouse skin: possible role of in-situ generated reactive oxygen species. Carcinogenesis 17:2023–2028

    Article  PubMed  CAS  Google Scholar 

  35. Flohe L, Gunzler W (1984) Assays of glutathione peroxidase. In: Colowick SP, Kaplan NO (eds) Methods Enzymology. Academic Press, New York, pp 114–121

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  37. Sedlak J, Lindsay RH (1968) Estimation of total protein bound and non protein bound SH groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205

    Article  PubMed  CAS  Google Scholar 

  38. Oliveira H, Spano M, Santos C, Mdel P (2009) Lead chloride affects sperm motility and acrosome reaction in mice. Cell Biolo Toxicol 25:341–353

    Article  CAS  Google Scholar 

  39. Sharma A, Sharma V, Kansal L (2010) Amelioration of lead-induced hepatotoxicity by Allium sativum extracts in Swiss albino mice. Libyan J Med. doi:10.4176/091107

    PubMed  Google Scholar 

  40. Ercal N, Gurer-Orhan H, Aykin-Burns N (2001) Toxic metals and oxidative stress. Part I. Mechanisms involved in metal induced oxidative damage. Curr Top Med Chem 1:529–539

    Article  PubMed  CAS  Google Scholar 

  41. Hsu PC, Liu MY, Hsu CC, Chen LY, Guo YL (1997) Lead exposure causes generation of reactive oxygen species and functional impairment in rat sperm. Toxicology 122:133–143

    Article  PubMed  CAS  Google Scholar 

  42. Komprda T (2012) Eicosapentaenoic and docosahexaenoic acids as inflammation-modulating and lipid homeostasis influencing nutraceuticals: a review. J Funct Foods 4:25–38

    Article  CAS  Google Scholar 

  43. Al-Nouri DM, Al-Khalifa AS, Shahidi F (2012) Long-term supplementation of dietary omega-6/omega-3 ratios alters bone marrow fatty acid and biomarkers of bone metabolism in growing rabbits. J Funct Foods 4:584–593

    Article  CAS  Google Scholar 

  44. Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM (2006) n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular beneWts. Am J Clin Nutr 83:1526S–1535S

    PubMed  CAS  Google Scholar 

  45. Harper CR, Edwards MJ, DeFilipis AP, Jacobson TA (2006) Flaxseed oil increases the plasma concentrations of cardioprotective (n-3) fatty acids in humans. J Nutr 136:83–87

    PubMed  CAS  Google Scholar 

  46. Lay C, Dybing D (1989) Linseed in oil crops of the world. In: Robbelen G, Downey R, Ashri A (eds.) McGraw Hill, New York, pp 121–129

  47. Harris R, Haggerty W (1993) Assays for potentially anticarcinogenic phytochemicals in flaxseed. Cereal Food World 38:147–151

    CAS  Google Scholar 

  48. Jadhav SH, Sarkar SN, Patil RD, Tripathi HC (2007) Effects of subchronic exposure via drinking water to a mixture of eight water-contaminating metals: a biochemical and histopathological study in male rats. Arch Environ Contam Toxicol 53:667–677

    Article  PubMed  CAS  Google Scholar 

  49. Jayakumar T, Sridhar MP, Bharathprasad TR, Ilayaraja M, Govindasamy S, Balasubramanian MP (2009) Experimental studies of Achyranthes aspera preventing nephrotoxicity induced by lead in albino rats. J Health Sci 55:701–708

    Article  CAS  Google Scholar 

  50. Pollack VE, Bonting SL, Muerhrcke RC, Kark RM (1960) Alkaline phosphatase and lactate dehydrogenase activities in renal tubular diseases. J Clin Invest 39:1386–1395

    Article  Google Scholar 

  51. Henry GE, Momin RA, Nair MG, Dewitt DL (2002) Antioxidant and cyclooxygenase activities of fatty acids found in food. J Agric Food Chem 50:2231–2234

    Article  PubMed  CAS  Google Scholar 

  52. Kukoba TV, Shysh AM, Moibenko OO, Kotsiuruba AV, Kharchenko OV (2006) The effects of alpha-linolenic acid on the functioning of the isolated heart during acute myocardial ischemia/reperfusion. Fiziol Zh 52(5):12–20

    PubMed  CAS  Google Scholar 

  53. Carrillo-Tripp M, Feller SE (2005) Evidence for a mechanism by which omega-3 polyunsaturated lipids may affect membrane protein function. Biochemistry 44:10164–10169

    Article  PubMed  CAS  Google Scholar 

  54. Lachant NA, Tomoda A, Tanaka KR (1984) Inhibition of the pentose phosphate shunt by lead: a potential mechanism for hemolysis in lead poisoning. Blood 63(3):518–524

    PubMed  CAS  Google Scholar 

  55. Sajitha GR, Jose R, Andrews A, Ajantha KG, Augustine P, Augusti KT (2010) Garlic oil and vitamin E prevent the adverse effects of lead acetate and ethanol separately as well as in combination in the drinking water of rats. Ind J Clin Biochem 25(3):280–288

    Article  CAS  Google Scholar 

  56. Sujatha K, Srilatha CH, Anjaneyulu Y, Amaravathi P (2011) Lead acetate induced nephrotoxicity in wistar albino rats, pathological, immunohistochemical and ultra structural studies. Int J Pharm Bio Sci 2(2):B459–B469

    Google Scholar 

  57. Vallee BL, Ulmer DD (1972) Biochemical effects of mercury, cadmium, and lead. Annu Rev Biochem 41:91–128

    Article  PubMed  CAS  Google Scholar 

  58. McGowan C, Donaldson WE (1986) Changes in organ non-protein sulfhydryl and glutathione concentrations during acute and chronic injection of inorganic lead to chicks. Biol Trace Elem Res 10:37–46

    Article  CAS  Google Scholar 

  59. Chiba M, Shinohara A, Matsushita K, Watanabe H, YIhaba Y (1996) Indices of lead-exposure in blood and urine of lead-exposed workers and concentrations of major and trace elements and activities of SOD, GSH-Px and catalase in their blood. Tohoku J Exp Med 178(1):49–62

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the University Grants Commission (UGC), New Delhi for the award of scholarships to SR (Junior Research Fellowship under Maulana Azad National Fellowship scheme) and AN. The authors are also thankful to Prof. A.N.K. Yusufi for his kind help in the course of this study.

Conflict of interest

The authors state no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Farah Khan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rizwan, S., Naqshbandi, A. & Khan, F. Dietary Flaxseed Oil Supplementation Mitigates the Effect of Lead on the Enzymes of Carbohydrate Metabolism, Brush Border Membrane, and Oxidative Stress in Rat Kidney Tissues. Biol Trace Elem Res 153, 279–290 (2013). https://doi.org/10.1007/s12011-013-9669-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-013-9669-9

Keywords

Navigation