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.
Curcumin Lead intoxication Immunoglobulins Gene expression Liver Kidney Histopathology
This is a preview of subscription content, log in to check access.
We greatly appreciate the contributions of all authors to finish this study.
Conflict of Interest
Authors declare no conflict of interests.
There is no financial support for this study and was supported on author’s expenses.
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
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
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/jf0723965PubMedCrossRefGoogle Scholar
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
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
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.12183PubMedCrossRefGoogle Scholar
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
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
Polyanskiy NG Fillipova NA ed. (1986) Analytical chemistry of the elements: lead. P.22Google Scholar
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
Williams BJ, Hejtmancik MR, Abreu M (1983) Cardiac effects of lead. Fed Proc 42:2989–2993PubMedGoogle Scholar
Jarrar BM (2003) Histological and histochemical alterations in the kidney induced by lead. Ann Saudi Med 23:10–15PubMedGoogle Scholar
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.2013.01.024PubMedCrossRefGoogle Scholar
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
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
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
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
Kriz W, Gretz N, Lemley KV (1998) Progression of glomerular diseases: is the podocyte the culprit? Kidney Int 54:687–697PubMedCrossRefGoogle Scholar
Omary MB, Coulombe PA, McLean WH (2004) Intermediate filament proteins and their associated diseases. N Engl J Med 351:2087–2100PubMedCrossRefGoogle Scholar
Arend W, Gab C (2004) Cytokines in the rheumatic diseases. Rev Rheumatol Dis Clin North Am 30:41–67CrossRefGoogle Scholar
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
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
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