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Biological Trace Element Research

, Volume 167, Issue 1, pp 91–102 | Cite as

Molecular and Histopathological Study on the Ameliorative Effects of Curcumin Against Lead Acetate-Induced Hepatotoxicity and Nephrototoxicity in Wistar Rats

  • Mohamed M. Soliman
  • Ahmed A. Baiomy
  • Magdy H. Yassin
Article

Abstract

Lead (Pb2+) toxicity is the most common form of heavy metal intoxication in humans and animals. Therefore, the current study was conducted to evaluate the potential ameliorative effects of curcumin on lead acetate (LA)-induced deleterious effects in the liver and kidney. Forty male Wistar rats were divided into four equal groups; first group was used as a control and given both corn oil orally and vehicle of lead acetate intraperitoneally (i.p). Groups from 2–4 were treated with lead acetate (LA; 50 mg/kg BW i.p), curcumin (200 mg/kg BW orally), and curcumin plus lead acetate, respectively. Curcumin was administered 3 weeks before LA injection for 7 days. Pb2+-intoxicated rats have higher Pb2+ levels compared to other treated groups. Results revealed that lead acetate significantly increased the serum levels of hepatic transaminases (GPT and GOT), urea and creatinine, while albumin was significantly decreased. In parallel, serum IgG, IgM, and IgA were significantly decreased in LA-injected rats. LA groups showed decrease in messenger RNA (mRNA) expression of catalase, SOD, GST, GPx, and alpha-1 acid glycoprotein (AGP), while the gene expression of desmin, vimentin, transforming growth factor-β1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1), and alpha-2 macroglobulin (α-2M) was increased. Prior and coadministration of curcumin with LA for 7 days significantly improved the ameliorated changes in liver and kidney, immunoglobulins, and mRNA expression. Moreover, curcumin ameliorated LA-induced congestion of hepatic and renal blood vessels and decreased fibrous tissue proliferation and necrosis of hepatocytes. In the kidney, LA-induced degeneration in tubular epithelium and intraluminal hyaline casts and prior curcumin administration restored normal renal structure with mild congestion of renal blood vessels. The results clarify the potential of curcumin to counteract the immunosuppressive alteration in gene expression as well as hepatic and renal damage occurred after Pb2+ intoxication.

Keywords

Curcumin Lead intoxication Immunoglobulins Gene expression Liver Kidney Histopathology 

Notes

Acknowledgments

We greatly appreciate the contributions of all authors to finish this study.

Conflict of Interest

Authors declare no conflict of interests.

Financial Disclosure

There is no financial support for this study and was supported on author’s expenses.

References

  1. 1.
    Landrigan PJ, Boffetta P, Apostoli P (2000) The reproductive toxicity and carcinogenicity of lead: a critical review. Am J Ind Med 38:231–243PubMedCrossRefGoogle Scholar
  2. 2.
    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. doi: 10.2174/1568026013394831 PubMedCrossRefGoogle Scholar
  3. 3.
    Silbergeld EK, Waalkes M, Rice JM (2000) Lead as a carcinogen: experimental evidence and mechanisms of action. Am J Ind Med 38:316–323PubMedCrossRefGoogle Scholar
  4. 4.
    El-Nekeety AA, El-Kady AA, Soliman MS, Hassan NS, Abdel-Wahhab MA (2009) Protective effect of Aquilegia vulgaris (L.) against lead acetate-induced oxidative stress in rats. Food Chem Toxicol 47:2209–15. doi: 10.1016/j.fct.2009.06.019 PubMedCrossRefGoogle Scholar
  5. 5.
    Flora SJS, Mittal M, Mehta A (2008) Heavy metal induced oxidative stress and its possible reversal by chelation therapy. Indian J Med Res 128:501–23PubMedGoogle Scholar
  6. 6.
    Kuhad A, Pilkhwal S, Sharma S, Tirkey N, Chopra K (2007) Effect of curcumin on inflammation and oxidative stress in cisplatin-induced experimental nephrotoxicity. J Agric Food Chem 55:10150–10155. doi: 10.1021/jf0723965 PubMedCrossRefGoogle Scholar
  7. 7.
    Joe B, Vijaykumar M, Lokesh BR (2004) Biological properties of curcumin-cellular and molecular mechanisms of action. Crit Rev Food Sci Nutr 44:97–111. doi: 10.1080/10408690490424702 PubMedCrossRefGoogle Scholar
  8. 8.
    Okada K, Wangpoengtrakul C, Tanaka T, Toyokuni S, Uchida S, Osawa T (2001) Curcumin and especially tetrahydrocurcumin ameliorate oxidative stress-induced renal injury in mice. J Nutr 131:2090–2095PubMedGoogle Scholar
  9. 9.
    Conterato GMM, Augusti PR, Somacal S, Einsfeld L, Sobieski R, Torres JR (2007) Effect of lead acetate on cytosolic thioredoxin reductase activity and oxidative stress parameters in rat kidneys. Basic Clin Pharmacol Toxicol 101:96–100PubMedCrossRefGoogle Scholar
  10. 10.
    Conterato GM, Quatrin A, Somacal S, Ruviaro AR, Vicentini J, Augusti PR et al (2014) Acute exposure to low lead levels and its implications on the activity and expression of cytosolic thioredoxin reductase in the kidney. Basic Clin Pharmacol Toxicol 114:476–84. doi: 10.1111/bcpt.12183 PubMedCrossRefGoogle Scholar
  11. 11.
    Abdou HM, Hassan MA (2014) Protective role of omega 3 polyunsaturated fatty acid against lead acetate induced toxicity in liver of female rats. Biomed Res Int 2014:435857. doi: 10.1155/2014/435857 PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Fu Y, Zheng S, Lin J, Ryerse J, Chen A (2008) Curcumin protects the rat liver from CCl4 caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation. Mol Pharmacol 73:399–409PubMedCrossRefGoogle Scholar
  13. 13.
    Garcia-Nino W, Tapia E, Zazueta C, Barrón Z, Pando R, García C et al (2013) Curcumin Pretreatment Prevents Potassium Dichromate-Induced Hepatotoxicity, Oxidative Stress, Decreased Respiratory Complex I Activity, and Membrane Permeability Transition Pore Opening. J Evi Com Med 1-19. doi: 10.1155/2013/424692
  14. 14.
    Soliman MM, Nassan MA, Ismail TA (2014) Immunohistochemical and molecular study on the protective effect of curcumin against hepatic toxicity induced by paracetamol in Wistar rats. BMC Complement Altern Med 14:457. doi: 10.1186/1472-6882-14-457 PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Wilson I, Gamble M (2008) The hematoxylins and eosins. In: Bancroft JD, Gamble M (eds) Theory and practice of histological techniques. Elsevier Health Sciences, London, UK; ISBN-10. www.expertconsultbook.com/expertconsult/…/linkTo
  16. 16.
    Carson F (1990) Histotechnology: a self-instructional text. 3rd edn. ASCP Press, Chicago, ISBN-10: 0891895817. P 400. www.ascp.org/…/Histotechnology-A-Self-Instructional-Text-3rd-Edition.
  17. 17.
    Polyanskiy NG Fillipova NA ed. (1986) Analytical chemistry of the elements: lead. P.22Google Scholar
  18. 18.
    Ercal N, Neal R, Treeratphan P, Lutz PM, Hammond TC, Dennery PA et al (2000) A role for oxidative stress in suppressing serum immunoglobulin levels in lead exposed Fisher 344 rats. Arch Environ Contam Toxicol 39:251–6PubMedCrossRefGoogle Scholar
  19. 19.
    Williams BJ, Hejtmancik MR, Abreu M (1983) Cardiac effects of lead. Fed Proc 42:2989–2993PubMedGoogle Scholar
  20. 20.
    Jarrar BM (2003) Histological and histochemical alterations in the kidney induced by lead. Ann Saudi Med 23:10–15PubMedGoogle Scholar
  21. 21.
    Del Rio D, Stewart AJ, Pellegrini N (2005) A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 15:316–28. doi: 10.1016/j.numecd.2005.05.003 PubMedCrossRefGoogle Scholar
  22. 22.
    Halliwell B, Gutteridge J (1990) Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol 186:1–85. doi: 10.1016/0076-6879(90)86093-B PubMedCrossRefGoogle Scholar
  23. 23.
    Mehana EE, Meki AR, Fazili KM (2012) Ameliorated effects of green tea extract on lead induced liver toxicity in rats. Exp Toxicol Pathol 64:291–295. doi: 10.1016/j.etp.2010.09.001 PubMedCrossRefGoogle Scholar
  24. 24.
    Chiang H, Chang H, Yao P, Chen Y, Jeng K, Wang J et al (2014) Sesamin reduces acute hepatic injury induced by lead coupled with lipopolysaccharide. J Chin Med Assoc 77:227–233. doi: 10.1016/j.jcma.2014.02.010 PubMedCrossRefGoogle Scholar
  25. 25.
    Ansari MA, Maayah ZH, Bakheet SA, El-Kadi AO, Korashy HM (2013) The role of aryl hydrocarbon receptor signaling pathway in cardiotoxicity of acute lead intoxication in vivo and in vitro rat model. Toxicology 306:40–49. doi: 10.1016/j.tox.2013.01.024 PubMedCrossRefGoogle Scholar
  26. 26.
    Mathews V, Binu P, Sauganth-Paul M, Abhilash M, Manju A, Nair R (2012) Hepatoprotective efficacy of curcumin against arsenic trioxide toxicity. Asian Pac J Trop Biomed 2:S706–S711. doi: 10.1016/S2221-1691(12)60300-1 CrossRefGoogle Scholar
  27. 27.
    García-Niño WR, Pedraza-Chaverrí J (2014) Protective effect of curcumin against heavy metals-induced liver damage. Food Chem Toxicol 69:182–201. doi: 10.1016/j.fct.2014.04.016 PubMedCrossRefGoogle Scholar
  28. 28.
    Hsiao CL, Wu KH, Wan KS (2011) Effects of environmental lead exposure on T-helper cell-specific cytokines in children. J Immunotoxicol 8:284–287. doi: 10.3109/1547691X.2011.592162 PubMedCrossRefGoogle Scholar
  29. 29.
    Colombo S, Buclin T, Décosterd LA, Telenti A, Furrer H, Lee BL et al (2006) Orosomucoid (alpha1-acid glycoprotein) plasma concentration and genetic variants: effects on human immunodeficiency virus protease inhibitor clearance and cellular accumulation. Clin Pharmacol Ther 80:307–318PubMedCrossRefGoogle Scholar
  30. 30.
    Anderson SP, Cattley RC, Corton JC (1999) Hepatic expression of acute-phase protein genes during carcinogenesis induced by peroxisome proliferators. Mol Carcinog 26:226–238PubMedCrossRefGoogle Scholar
  31. 31.
    Lyoumi S, Tamion F, Petit J, Déchelotte P, Dauguet C, Scotté M et al (1998) Induction and modulation of acute-phase response by protein malnutrition in rats: comparative effect of systemic and localized inflammation on interleukin-6 and acute-phase protein synthesis. J Nutr 128:166–174PubMedGoogle Scholar
  32. 32.
    Fries JW, Sandstrom DJ, Meyer TW, Rennke HG (1989) Glomerular hypertrophy and epithelial cell injury modulate progressive glomerulosclerosis in the rat. Lab Investig 60:205–218PubMedGoogle Scholar
  33. 33.
    Kriz W, Gretz N, Lemley KV (1998) Progression of glomerular diseases: is the podocyte the culprit? Kidney Int 54:687–697PubMedCrossRefGoogle Scholar
  34. 34.
    DePianto D, Coulombe PA (2004) Intermediate filaments and tissue repair. Exp Cell Res 301:68–76PubMedCrossRefGoogle Scholar
  35. 35.
    Omary MB, Coulombe PA, McLean WH (2004) Intermediate filament proteins and their associated diseases. N Engl J Med 351:2087–2100PubMedCrossRefGoogle Scholar
  36. 36.
    Arend W, Gab C (2004) Cytokines in the rheumatic diseases. Rev Rheumatol Dis Clin North Am 30:41–67CrossRefGoogle Scholar
  37. 37.
    Jobin C, Braham C, Russo MP, Juma B, Narula AS, Brenner DA et al (1999) Curcumin blocks cytokine-mediated NF-κB activation and proinflammatory gene expression by inhibiting inhibitory factor I-κB kinase activity. J Immunol 163:3474–3483PubMedGoogle Scholar
  38. 38.
    Qiao YF, Jiang YS, Pang DZ (2006) Expression of renal nuclear factor-kappa B, transforming growth factor-beta and fibronectin of rats exposed to lead. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 3:139–42Google Scholar
  39. 39.
    Gerdprasert O, O’Bryan MK, Nikolic-Paterson DJ, Sebire K, de Kretser DM, Hedger MP (2002) Expression of monocyte chemoattractant protein-1 and macrophage colony-stimulating factor in normal and inflamed rat testis. Mol Hum Reprod 8:518–24PubMedCrossRefGoogle Scholar
  40. 40.
    Ghoniem M, El-Sharkawy N, Hussein M, Moustafa G (2012) Efficacy of Curcumin on Lead Induced Nephrotoxicity in Female Albino Rats. Am Sci J 8:502-510. www.jofamericanscience.org/journals/…/064_8969am0806_502_510.pdf
  41. 41.
    Agarwal R, Goel SK, Behari JR (2010) Detoxification and antioxidant effects of curcumin in rats experimentally exposed to mercury. J Appl Toxicol 30:457–468. doi: 10.1002/jat.1517 PubMedGoogle Scholar
  42. 42.
    Flora G, Gupta D, Tiwari A (2012) Toxicity of lead: a review with recent updates. Interdiscip Toxicol 5:47–58. doi: 10.2478/v10102-012-0009-2 PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Mohamed M. Soliman
    • 1
    • 2
  • Ahmed A. Baiomy
    • 3
    • 4
  • Magdy H. Yassin
    • 3
    • 5
  1. 1.Medical Laboratory Department, Faculty of Applied Medical SciencesTaif UniversityTurabahSaudi Arabia
  2. 2.Department of Biochemistry, Faculty of Veterinary MedicineBenha UniversityBenhaEgypt
  3. 3.Biology Department, Faculty of ScienceTaif UniversityTurabahSaudi Arabia
  4. 4.Zoology Department, Faculty of ScienceCairo UniversityGizaEgypt
  5. 5.Reproductive Diseases DepartmentAnimal Reproduction Research InstituteGizaEgypt

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