Evaluation of protective efficacy of flaxseed lignan-Secoisolariciresinol diglucoside against mercuric chloride-induced nephrotoxicity in rats

  • Tareq Aqeel
  • Sunil Chikkalakshmipura Gurumallu
  • Saeed Mujahid Hashimi
  • Naif AlQurashi
  • Rajesh JavaraiahEmail author
Original Article


The toxicity of heavy metals such as mercury (Hg) in humans and animals is well documented. The kidney is the primary deposition site of inorganic-Hg and target organ of its toxicity. The present study investigated the protective efficacy of flaxseed lignan-Secoisolariciresinol diglucoside (SDG) on nephrotoxicity induced by mercuric chloride (HgCl2). Rats were intraperitoneally injected with HgCl2 (2 mg/kg/day) and renal toxicity was induced. Subcutaneous administration of rats with SDG (5 mg/kg/day) as a pre-treatment caused a significant reversal of HgCl2 induced increase in blood urea, creatinine, glutathione s-transferase and catalase (CAT). On the other hand, administration of SDG with HgCl2 restored normal levels of albumin and superoxide dismutase (SOD). Histological examination of kidneys confirmed that pre-treatment of SDG before HgCl2 administration significantly reduced its pathological effects. Thus, the results of the present investigation suggest that SDG can significantly reduce renal damage, serum and tissue biochemical profiles caused by HgCl2 induced nephrotoxicity. Hence, SDG may be recommended for clinical trials in the treatment of kidney disorders caused by exposure to Hg.


Mercuric chloride Flaxseed lignan Secoisolariciresinol diglucoside Oxidative stress Nephrotoxicity 



Dr. JR is grateful for the financial assistance provided by the Department of Science & Technology, Government of India, New Delhi, to carry out this research work. The authors are thankful to Yuvaraja’s College, University of Mysore, Mysuru, India for providing the facilities to carry out this research work and also In vivo Biosciences, Kodigehalli, Bengaluru, India providing animals for the study. This research work was partially supported by Department of Science and Technology, Government of India, New Delhi, India.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no any conflict of interest.


  1. 1.
    Klaassen CD, Watkins JB (1996) Casarett and Doull’s toxicology: the basic science of poisons, vol 5. McGraw-Hill, New YorkGoogle Scholar
  2. 2.
    Şener G, Şehirli AÖ, Ayanogˇlu-Dülger G (2003) Melatonin protects against mercury (II)-induced oxidative tissue damage in rats. Pharmacol Toxicol 93(6):290–296. Google Scholar
  3. 3.
    Mahboob M, Shireen KF, Atkinson A, Khan AT (2001) Lipid peroxidation and antioxidant enzyme activity in different organs of mice exposed to low level of mercury. J Environ Sci Health B 36(5):687–697. Google Scholar
  4. 4.
    Dátilo MN, SantAna MR, Formigari GP, Rodrigues PB, de Moura LP, da Silva ASR, Ropelle ER, Pauli JR, Cintra DE (2018) Omega-3 from flaxseed oil protects obese mice against diabetic retinopathy through GPR120 receptor. Sci Rep 8(1):14318Google Scholar
  5. 5.
    Emanuelli T, Rocha J, Pereira M, Porciuncula L, Morsch V, Martins A, Souza D (1996) Effect of mercuric chloride intoxication and dimercaprol treatment on σ-aminolevulinate dehydratase from brain, liver and kidney of adult mice. Pharmacol Toxicol 79(3):136–143. Google Scholar
  6. 6.
    Tanaka-Kagawa T, Suzuki M, Naganuma A, Yamanaka N, Imura N (1998) Strain difference in sensitivity of mice to renal toxicity of inorganic mercury. J Pharmacol Exp Ther 285(1):335–341Google Scholar
  7. 7.
    Zalups RK (2000) Molecular interactions with mercury in the kidney. Pharmacol Rev 52(1):113–144Google Scholar
  8. 8.
    Clarkson TW (1997) The toxicology of mercury. Crit Rev Clin Lab Sci 34(4):369–403. Google Scholar
  9. 9.
    Li Z, Wu J, DeLeo CJ (2006) RNA damage and surveillance under oxidative stress. IUBMB Life 58(10):581–588. Google Scholar
  10. 10.
    Patrick L (2002) Mercury toxicity and antioxidants: part I role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity-mercury toxicity. Toxicol Appl Pharmacol 7:456–471Google Scholar
  11. 11.
    Pillai A, Gupta S (2005) Antioxidant enzyme activity and lipid peroxidation in liver of female rats co-exposed to lead and cadmium: effects of vitamin E and Mn2+. Free Radic Res 39(7):707–712. Google Scholar
  12. 12.
    Agarwal R, Goel SK, Behari JR (2010) Detoxification and antioxidant effects of curcumin in rats experimentally exposed to mercury. J Appl Toxicol 30(5):457–468. Google Scholar
  13. 13.
    Agarwal R, Goel SK, Chandra R, Behari JR (2010) Role of vitamin E in preventing acute mercury toxicity in rat. Environ Toxicol Pharmacol 29(1):70–78. Google Scholar
  14. 14.
    Nava M, Romero F, Quiroz Y, Parra G, Bonet L, Rodríguez-Iturbe B (2000) Melatonin attenuates acute renal failure and oxidative stress induced by mercuric chloride in rats. Am J Physiol-Renal Physiol 279(5):F910–F918. Google Scholar
  15. 15.
    Ahn CB, Song CH, Kim WH, Kim YK (2002) Effects of Juglans sinensis dode extract and antioxidant on mercury chloride-induced acute renal failure in rabbits. J Ethnopharmacol 82(1):45–49. Google Scholar
  16. 16.
    Oda SS, El-Ashmawy IM (2012) Adverse effects of the anabolic steroid, boldenone undecylenate, on reproductive functions of male rabbits. Int J Exp Pathol 93(3):172–178. Google Scholar
  17. 17.
    Hosseini A, Rajabian A, Fanoudi S, Farzadnia M, Boroushaki MT (2018) Protective effect of Rheum turkestanicum root against mercuric chloride-induced hepatorenal toxicity in rats. Avicenna J Phytomed 8:1–11Google Scholar
  18. 18.
    Bhathena SJ, Velasquez MT (2002) Beneficial role of dietary phytoestrogens in obesity and diabetes. Am J Clin Nutr 76(6):1191–1201. Google Scholar
  19. 19.
    Duncan AM, Phipps WR, Kurzer MS (2003) Phyto-oestrogens. Best Pract Res Clin Endocrinol Metab 17(2):253–271. Google Scholar
  20. 20.
    Pan A, Sun J, Chen Y, Ye X, Li H, Yu Z, Wang Y, Gu W, Zhang X, Chen X (2007) Effects of a flaxseed-derived lignan supplement in type 2 diabetic patients: a randomized, double-blind, cross-over trial. PLoS ONE 2(11):e1148. Google Scholar
  21. 21.
    Prasad K (1999) Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed. Circulation 99(10):1355–1362. Google Scholar
  22. 22.
    DeLuca JA, Garcia-Villatoro EL, Allred CD (2018) Flaxseed bioactive compounds and colorectal cancer prevention. Curr Oncol Rep 20(8):59. Google Scholar
  23. 23.
    Kurzer MS, Xu X (1997) Dietary phytoestrogens. Annu Rev Nutr 17(1):353–381. Google Scholar
  24. 24.
    Moree SS, Rajesha J (2013) Investigation of in vitro and in vivo antioxidant potential of secoisolariciresinol diglucoside. Mol Cell Biochem 373(1–2):179–187. Google Scholar
  25. 25.
    Moree SS, Kavishankar G, Rajesha J (2013) Antidiabetic effect of secoisolariciresinol diglucoside in streptozotocin-induced diabetic rats. Phytomedicine 20(3–4):237–245. Google Scholar
  26. 26.
    Prasad K (1997) Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flax-seed. Mol Cell Biochem 168(1–2):117–123. Google Scholar
  27. 27.
    Rajesha J, Murthy KNC, Kumar MK, Madhusudhan B, Ravishankar GA (2006) Antioxidant potentials of flaxseed by in vivo model. J Agric Food Chem 54(11):3794–3799. Google Scholar
  28. 28.
    Han H, Yılmaz H, Gülçin İ (2018) Antioxidant activity of flaxseed (Linum usitatissimum L.) shell and analysis of its polyphenol contents by LC-MS/MS. Rec Nat Prod 12(4):397–402. Google Scholar
  29. 29.
    Prasad K (2000) Oxidative stress as a mechanism of diabetes in diabetic BB prone rats: effect of secoisolariciresinol diglucoside (SDG). Mol Cell Biochem 209(1–2):89–96. Google Scholar
  30. 30.
    Prasad K (2001) Secoisolariciresinol diglucoside from flaxseed delays the development of type 2 diabetes in Zucker rat. J Lab Clin Med 138(1):32–39. Google Scholar
  31. 31.
    Adolphe JL, Whiting SJ, Juurlink BH, Thorpe LU, Alcorn J (2010) Health effects with consumption of the flax lignan secoisolariciresinol diglucoside. Br J Nutr 103(7):929–938. Google Scholar
  32. 32.
    Johnsson P, Kamal-Eldin A, Lundgren LN, Åman P (2000) HPLC method for analysis of secoisolariciresinol diglucoside in flaxseeds. J Agric Food Chem 48(11):5216–5219. Google Scholar
  33. 33.
    Heinegård D, Tiderström G (1973) Determination of serum creatinine by a direct colorimetric method. Clin Chim Acta 43(3):305–310. Google Scholar
  34. 34.
    Hallett C, Cook J (1971) Reduced nicotinamide adenine dinucleotide-coupled reaction for emergency blood urea estimation. Clin Chim Acta 35(1):33–37. Google Scholar
  35. 35.
    Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47(2):389–394. Google Scholar
  36. 36.
    Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases the first enzymatic step in mercapturic acid formation. J Biol Chem 249(22):7130–7139Google Scholar
  37. 37.
    Hazelhoff MH, Bulacio RP, Chevalier A, Torres AM (2018) Renal expression of organic anion transporters is modified after mercuric chloride exposure: gender-related differences. Toxicol Lett 295:390–396. Google Scholar
  38. 38.
    Karapehlivan M, Ogun M, Kaya I, Ozen H, Deveci HA, Karaman M (2014) Protective effect of omega-3 fatty acid against mercury chloride intoxication in mice. J Trace Elem Med Biol 28(1):94–99. Google Scholar
  39. 39.
    Al-Saleh I, El-Doush I, Shinwari N, Al-Baradei R, Khogali F, Al-Amodi M (2005) Does low mercury containing skin-lightening cream (fair & lovely) affect the kidney, liver, and brain of female mice? Cutan Ocul Toxicol 24(1):11–29. Google Scholar
  40. 40.
    Augusti PR, Conterato GM, Somacal S, Einsfeld L, Ramos AT, Hosomi FY, Graça DL, Emanuelli T (2007) Effect of lycopene on nephrotoxicity induced by mercuric chloride in rats. Basic Clin Pharmacol Toxicol 100(6):398–402. Google Scholar
  41. 41.
    Rumbeiha WK, Fitzgerald SD, Braselton WE, Roth RA, Kaneene JB (2000) Potentiation of mercury-induced nephrotoxicity by endotoxin in the Sprague-Dawley rat. Toxicology 149(2–3):75–87. Google Scholar
  42. 42.
    Carmignani M, Boscolo P, Artese L, Del Rosso G, Porcelli G, Felaco M, Volpe AR, Giuliano G (1992) Renal mechanisms in the cardiovascular effects of chronic exposure to inorganic mercury in rats. Occup Environ Med 49(4):226–232. Google Scholar
  43. 43.
    Langeswaran K, Selvaraj J, Ponnulakshmi R, Mathaiyan M, Vijayaprakash S (2018) Protective effect of Kaempferol on biochemical and histopathological changes in mercuric chloride induced nephrotoxicity in experimental rats. J Biol Active Prod Nat 8(2):125–136. Google Scholar
  44. 44.
    Bigazzi PE (1992) Lessons from animal models: the scope of mercury-induced autoimmunity. Clin Immunol Immunopathol 65(2):81. Google Scholar
  45. 45.
    Girardi G, Elias MM (1995) Mercuric chloride effects on rat renal redox enzymes activities: SOD protection. Free Radic Biol Med 18(1):61–66. Google Scholar
  46. 46.
    Fouda AMM, Daba MHY, Dahab GM, Sharaf el-Din OA (2008) Thymoquinone ameliorates renal oxidative damage and proliferative response induced by mercuric chloride in rats. Basic Clin Pharmacol Toxicol 103(2):109–118. Google Scholar
  47. 47.
    Augusti P, Conterato G, Somacal S, Sobieski R, Spohr P, Torres J, Charão M, Moro A, Rocha M, Garcia S (2008) Effect of astaxanthin on kidney function impairment and oxidative stress induced by mercuric chloride in rats. Food Chem Toxicol 46(1):212–219. Google Scholar
  48. 48.
    Aslanturk A, Uzunhisarcikli M, Kalender S, Demir F (2014) Sodium selenite and vitamin E in preventing mercuric chloride induced renal toxicity in rats. Food Chem Toxicol 70:185–190. Google Scholar
  49. 49.
    Uyemura SA, Santos NA, Mingatto FE, Curti C (1997) Hg (II)-induced renal cytotoxicity: in vitro and in vivo implications for the bioenergetic and oxidative status of mitochondria. Mol Cell Biochem 177(1–2):53–59. Google Scholar
  50. 50.
    Brzóska M, Moniuszko-Jakoniuk J, Jurczuk M, Gałażyn-Sidorczuk M (2002) Cadmium turnover and changes of zinc and copper body status of rats continuously exposed to cadmium and ethanol. Alcohol Alcohol 37(3):213–221. Google Scholar
  51. 51.
    Salo DC, Lin SW, Pacifici RE, Davies KJ (1988) Superoxide dismutase is preferentially degraded by a proteolytic system from red blood cells following oxidative modification by hydrogen peroxide. Free Radic Biol Med 5(5–6):335–339. Google Scholar
  52. 52.
    Rom S, Zuluaga-Ramirez V, Reichenbach NL, Erickson MA, Winfield M, Gajghate S, Christofidou-Solomidou M, Jordan-Sciutto KL, Persidsky Y (2018) Secoisolariciresinol diglucoside is a blood-brain barrier protective and anti-inflammatory agent: implications for neuroinflammation. J Neuroinflamm 15(1):25. Google Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Biochemistry, Yuvaraja’s CollegeUniversity of MysoreMysuruIndia
  2. 2.Department of Basic Science, Biology Unit Deanship of Preparatory Year and Supporting studiesImam Abdulrahman Bin Faisal UniversityDammamSaudi Arabia

Personalised recommendations