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

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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.

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References

  1. Landrigan PJ, Boffetta P, Apostoli P (2000) The reproductive toxicity and carcinogenicity of lead: a critical review. Am J Ind Med 38:231–243

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  3. Silbergeld EK, Waalkes M, Rice JM (2000) Lead as a carcinogen: experimental evidence and mechanisms of action. Am J Ind Med 38:316–323

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  5. Flora SJS, Mittal M, Mehta A (2008) Heavy metal induced oxidative stress and its possible reversal by chelation therapy. Indian J Med Res 128:501–23

    CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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 131:2090–2095

    CAS  PubMed  Google Scholar 

  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 101:96–100

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed Central  PubMed  Google Scholar 

  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 73:399–409

    Article  CAS  PubMed  Google Scholar 

  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. 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

    Article  PubMed Central  PubMed  Google Scholar 

  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. 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. Polyanskiy NG Fillipova NA ed. (1986) Analytical chemistry of the elements: lead. P.22

  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 39:251–6

    Article  CAS  PubMed  Google Scholar 

  19. Williams BJ, Hejtmancik MR, Abreu M (1983) Cardiac effects of lead. Fed Proc 42:2989–2993

    CAS  PubMed  Google Scholar 

  20. Jarrar BM (2003) Histological and histochemical alterations in the kidney induced by lead. Ann Saudi Med 23:10–15

    PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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 80:307–318

    Article  CAS  PubMed  Google Scholar 

  30. Anderson SP, Cattley RC, Corton JC (1999) Hepatic expression of acute-phase protein genes during carcinogenesis induced by peroxisome proliferators. Mol Carcinog 26:226–238

    Article  CAS  PubMed  Google Scholar 

  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 128:166–174

    CAS  PubMed  Google Scholar 

  32. Fries JW, Sandstrom DJ, Meyer TW, Rennke HG (1989) Glomerular hypertrophy and epithelial cell injury modulate progressive glomerulosclerosis in the rat. Lab Investig 60:205–218

    CAS  PubMed  Google Scholar 

  33. Kriz W, Gretz N, Lemley KV (1998) Progression of glomerular diseases: is the podocyte the culprit? Kidney Int 54:687–697

    Article  CAS  PubMed  Google Scholar 

  34. DePianto D, Coulombe PA (2004) Intermediate filaments and tissue repair. Exp Cell Res 301:68–76

    Article  CAS  PubMed  Google Scholar 

  35. Omary MB, Coulombe PA, McLean WH (2004) Intermediate filament proteins and their associated diseases. N Engl J Med 351:2087–2100

    Article  CAS  PubMed  Google Scholar 

  36. Arend W, Gab C (2004) Cytokines in the rheumatic diseases. Rev Rheumatol Dis Clin North Am 30:41–67

    Article  Google Scholar 

  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 163:3474–3483

    CAS  PubMed  Google Scholar 

  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 3:139–42

    Google Scholar 

  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 8:518–24

    Article  CAS  PubMed  Google Scholar 

  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. 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

    CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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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.

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Authors and Affiliations

  1. Medical Laboratory Department, Faculty of Applied Medical Sciences, Taif University, Turabah, Saudi Arabia

    Mohamed M. Soliman

  2. Department of Biochemistry, Faculty of Veterinary Medicine, Benha University, P.O. 13736, Moshtohor, Benha, Egypt

    Mohamed M. Soliman

  3. Biology Department, Faculty of Science, Taif University, Turabah, Saudi Arabia

    Ahmed A. Baiomy & Magdy H. Yassin

  4. Zoology Department, Faculty of Science, Cairo University, Giza, Egypt

    Ahmed A. Baiomy

  5. Reproductive Diseases Department, Animal Reproduction Research Institute, Al-Haram, Giza, Egypt

    Magdy H. Yassin

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  1. Mohamed M. Soliman
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Correspondence to Mohamed M. Soliman.

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Soliman, M.M., Baiomy, A.A. & Yassin, M.H. Molecular and Histopathological Study on the Ameliorative Effects of Curcumin Against Lead Acetate-Induced Hepatotoxicity and Nephrototoxicity in Wistar Rats. Biol Trace Elem Res 167, 91–102 (2015). https://doi.org/10.1007/s12011-015-0280-0

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