Skip to main content
Log in

Oxidative Stress Markers and Histological Analysis in Diverse Organs from Rats Treated with a Hepatotoxic Dose of Cr(VI): Effect of Curcumin

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

Abstract

Hexavalent chromium [Cr(VI)] compounds are extremely toxic and carcinogenic. Despite the vast quantity of reports about Cr(VI) toxicity, the information regarding its effects when it is intraperitoneally (i.p.) administered is still limited. In contrast, it has been shown that curcumin prevents hepatotoxicity induced by a single intraperitoneal injection of 15 mg/kg body weight (b.w.) of potassium dichromate (K2Cr2O7). This study aims to evaluate oxidative stress markers, the activity of antioxidant enzymes, and the potential histological injury in brain, heart, lung, kidney, spleen, pancreas, stomach, and intestine from rats treated with a hepatotoxic dose of K2Cr2O7 (15 mg/kg b.w.), and the effect of curcumin pretreatment. Rats were divided into four groups: control, curcumin, K2Cr2O7, and curcumin+K2Cr2O7. At the end of the treatment, plasma and ascites fluid were collected and target organs were dissected out for biochemical and histological analysis. K2Cr2O7 induced hepatotoxicity but failed to induce in all the other studied organs either oxidative or histological injury, since levels of malondialdehyde (MDA), glutathione (GSH), and the activity of superoxide dismutase (SOD), catalase (CAT), and related GSH enzymes were unchanged. As expected, curcumin was safe. Lack of K2Cr2O7-induced toxicity in those target organs could be due to the following: (1) route of administration, (2) absorption through the portal circulation, (3) lower dose than needed, (4) short time of exposure, or (5) repeated doses are required to produce damage. Thus, the intraperitoneal injection of 15 mg/kg of K2Cr2O7, that is able to induce hepatotoxicity, was unable to induce histological and oxidative damage in other target organs.

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
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Codd R, Dillon CT, Levina A, Lay PA (2001) Studies on the genotoxicity of chromium: from the test tube to the cell. Coord Chem Rev 216–217:537–582

    Article  Google Scholar 

  2. Bagchi D, Stohs S, Downs B et al (2002) Cytotoxicity and oxidative mechanisms of different forms of chromium. Toxicology 180:5–22

    Article  CAS  PubMed  Google Scholar 

  3. Zhang X-H, Zhang X, Wang X-C et al (2011) Chronic occupational exposure to hexavalent chromium causes DNA damage in electroplating workers. BMC Public Health 11:224. doi:10.1186/1471-2458-11-224

    Article  PubMed Central  PubMed  Google Scholar 

  4. NIOSH (2013) Criteria for a recommended standard occupational exposure to hexavalent chromium. CDC - U.S. Department of Health and Human Services and Centers for Disease Control and Prevention NIOSH - National Institute for Occupational Safety and Health. 168

  5. ATSDR (2012) Toxicological profile for chromium. U.S. Public Health Service, Agency for Toxic Substances and Disease Registry. 592

  6. OEHHA (2009) Evidence on the developmental and reproductive toxicity of chromium (hexavalent compounds). Reproductive and Cancer Hazard Assessment Section. Office of Environmental Health Hazard Assessment. 97

  7. Saeidnia S, Abdollahi M (2013) Antioxidants: friends or foe in prevention or treatment of cancer: the debate of the century. Toxicol Appl Pharmacol 271:49–63. doi:10.1016/j.taap.2013.05.004

    Article  CAS  PubMed  Google Scholar 

  8. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4:807–818

    Article  CAS  PubMed  Google Scholar 

  9. Ak T, Gülcin I (2008) Antioxidant and radical scavenging properties of curcumin. Chem Biol Interact 174:27–37. doi:10.1016/j.cbi.2008.05.003

    Article  CAS  PubMed  Google Scholar 

  10. 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 

  11. Nabavi SF, Daglia M, Moghaddam AH et al (2014) Curcumin and liver disease: from chemistry to medicine. Compr Rev Food Sci Food Saf 13:62–77. doi:10.1111/1541-4337.12047

    Article  CAS  Google Scholar 

  12. García-Niño WR, Tapia E, Zazueta C et al (2013) Curcumin pretreatment prevents potassium dichromate-induced hepatotoxicity, oxidative stress, decreased respiratory complex I activity, and membrane permeability transition pore opening. Evid Based Complem Altern Med 2013:424692

    Article  Google Scholar 

  13. García-Niño WR, Zazueta C, Tapia E, Pedraza-Chaverrí J (2014) Curcumin attenuates Cr(VI)-induced ascites and changes in the activity of aconitase and F1F0 ATPase and the ATP content in rat liver mitochondria. J Biochem Mol Toxicol 28:522–527. doi:10.1002/jbt

    Article  PubMed  Google Scholar 

  14. Laborda R, Díaz-Mayans J, Núñez A (1986) Nephrotoxic and hepatotoxic effects of chromium compounds in rats. Bull Environ Contam Toxicol 36:332–336

    Article  CAS  PubMed  Google Scholar 

  15. Patlolla AK, Barnes C, Yedjou C et al (2009) Oxidative stress, DNA damage, and antioxidant enzyme activity induced by hexavalent chromium in Sprague–Dawley rats. Environ Toxicol 24:66–73

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Lowry O, Rosebrough N, Farr A, Randall R (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  17. Doumas BT, Watson WA, Biggs HG (1971) Albumin standards and the measurement of serum albumin with bromocresol green. Clin Chim Acta 31:87–96

    Article  CAS  PubMed  Google Scholar 

  18. Gómez-Sierra T, Molina-Jijón E, Tapia E et al (2014) S-allylcysteine prevents cisplatin-induced nephrotoxicity and oxidative stress. J Pharm Pharmacol 66:1271–1281. doi:10.1111/jphp.12263

    Article  PubMed  Google Scholar 

  19. Tapia E, Soto V, Ortiz-Vega K et al (2012) Curcumin induces Nrf2 nuclear translocation and prevents glomerular hypertension, hyperfiltration, oxidant stress, and the decrease in antioxidant enzymes in 5/6 nephrectomized rats. Oxid Med Cell Longev 2012:269039. doi:10.1155/2012/269039

    Article  PubMed Central  PubMed  Google Scholar 

  20. Boşgelmez II, Söylemezoğlu T, Güvendik G (2008) The protective and antidotal effects of taurine on hexavalent chromium-induced oxidative stress in mice liver tissue. Biol Trace Elem Res 125:46–58. doi:10.1007/s12011-008-8154-3

    Article  PubMed  Google Scholar 

  21. Robin S, Sunil K, Rana AC, Nidhi S (2012) Different models of hepatotoxicity and related liver diseases: a review. Int Res J Pharm 3:86–95

    Google Scholar 

  22. Henkler F, Brinkmann J, Luch A (2010) The role of oxidative stress in carcinogenesis induced by metals and xenobiotics. Cancers (Basel) 2:376–396

    Article  CAS  Google Scholar 

  23. Ueno S, Kashimoto T, Susa N et al (2001) Detection of dichromate (VI)-induced DNA strand breaks and formation of paramagnetic chromium in multiple mouse organs. Toxicol Appl Pharmacol 170:56–62

    Article  CAS  PubMed  Google Scholar 

  24. Coudray C, Faure P, Rachidi S et al (1992) Hydroxyl radical formation and lipid peroxidation enhancement by chromium. In vitro study. Biol Trace Elem Res 32:161–170

    Article  CAS  PubMed  Google Scholar 

  25. Valko M, Morris H, Cronin MTD (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12:1161–1208

    Article  CAS  PubMed  Google Scholar 

  26. Nudler S, Quinteros F, Miler E et al (2009) Chromium VI administration induces oxidative stress in hypothalamus and anterior pituitary gland from male rats. Toxicol Lett 185:187–192. doi:10.1016/j.toxlet.2009.01.003

    Article  CAS  PubMed  Google Scholar 

  27. Chang H-R, Tsao D-A, Tseng W-C (2011) Hexavalent chromium inhibited the expression of RKIP of heart in vivo and in vitro. Toxicol In Vitro 25:1–6. doi:10.1016/j.tiv.2010.06.012

    Article  CAS  PubMed  Google Scholar 

  28. Beaver L, Stemmy E, Constant S et al (2009) Lung injury, inflammation and Akt signaling following inhalation of particulate hexavalent chromium. Toxicol Appl Pharmacol 235:47–56. doi:10.1016/j.taap.2008.11.018

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Hojo Y, Satomi Y (1991) In vivo nephrotoxicity induced in mice by chromium(VI). Involvement of glutathione and chromium(V). Biol Trace Elem Res 31:21–31

    Article  CAS  PubMed  Google Scholar 

  30. Matos RC, Bessa M, Oliveira H et al (2013) Mechanisms of kidney toxicity for chromium- and arsenic-based preservatives: potential involvement of a pro-oxidative pathway. Environ Toxicol Pharmacol 36:929–936. doi:10.1016/j.etap.2013.08.006

    Article  CAS  PubMed  Google Scholar 

  31. Dey SK, Roy S (2009) Effect of chromium on certain aspects of cellular toxicity. Iran J Toxicol 2:260–267. doi:10.1093/jicru/ndp032

    Google Scholar 

  32. El-Saad AMA, Abdel-Moneim A, Abdel-Karim HM (2010) N-acetylcysteine an allium plant compound protects against chromium (VI) induced oxidant stress and ultrastructural changes of pancreatic beta-cells in rats. J Med Plants Res 4:2290–2297

    Google Scholar 

  33. Thompson CM, Proctor DM, Suh M et al (2013) Assessment of the mode of action underlying development of rodent small intestinal tumors following oral exposure to hexavalent chromium and relevance to humans. Crit Rev Toxicol 43:244–274. doi:10.3109/10408444.2013.768596

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Aruldhas M, Subramanian S, Sekar P et al (2005) Chronic chromium exposure-induced changes in testicular histoarchitecture are associated with oxidative stress: study in a non-human primate (Macaca radiata Geoffroy). Hum Reprod 20:2801–2813. doi:10.1093/humrep/dei148

    Article  CAS  PubMed  Google Scholar 

  35. Sutherland JE, Zhitkovich a, Kluz T, Costa M (2000) Rats retain chromium in tissues following chronic ingestion of drinking water containing hexavalent chromium. Biol Trace Elem Res 74:41–53. doi:10.1385/BTER:74:1:41

    Article  CAS  PubMed  Google Scholar 

  36. Kim E, Na K (1991) Nephrotoxicity of sodium dichromate depending on the route of administration. Arch Toxicol 65:537–541

    Article  CAS  PubMed  Google Scholar 

  37. Singh A, Bhat TK, Sharma OP (2011) Clinical biochemistry of hepatotoxicity. J Clin Toxicol S 4:1–19. doi:10.4172/2161-0495.S4-001

    Google Scholar 

  38. Erez A, Shental O, Tchebiner JZ et al (2014) Diagnostic and prognostic value of very high serum lactate dehydrogenase in admitted medical patients. Isr Med Assoc J 16:439–443

    PubMed  Google Scholar 

  39. Krier M, Ahmed A (2009) The asymptomatic outpatient with abnormal liver function tests. Clin Liver Dis 13:167–177. doi:10.1016/j.cld.2009.02.001

    Article  PubMed  Google Scholar 

  40. McMillan HJ, Gregas M, Darras BT, Kang PB (2011) Serum transaminase levels in boys with Duchenne and Becker muscular dystrophy. Pediatrics 127:e132–e136. doi:10.1542/peds. 2010-0929

    Article  PubMed  Google Scholar 

  41. Solis-Heredia MJ, Quintanilla-Vega B, Sierra-Santoyo A et al (2000) Chromium increases pancreatic metallothionein in the rat. Toxicology 142:111–117

    Article  CAS  PubMed  Google Scholar 

  42. Balakrishnan R, Satish Kumar CSV, Usha Rani M (2013) Evaluation of protective action of a-tocopherol in chromium-induced oxidative stress in female reproductive system of rats. J Nat Sci Biol Med 4:87–93. doi:10.4103/0976-9668.107266

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Daniel S, Limson JL, Dairam A et al (2004) Through metal binding, curcumin protects against lead- and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain. J Inorg Biochem 98:266–275

    Article  CAS  PubMed  Google Scholar 

  44. Roshan VD, Assali M, Moghaddam AH et al (2011) Exercise training and antioxidants: effects on rat heart tissue exposed to lead acetate. Int J Toxicol 30:190–196. doi:10.1177/1091581810392809

    Article  CAS  PubMed  Google Scholar 

  45. Rennolds J, Malireddy S, Hassan F et al (2013) Curcumin regulates airway epithelial cell cytokine responses to the pollutant cadmium. Biochem Biophys Res Commun 417:256–261. doi:10.1016/j.bbrc.2011.11.096.Curcumin

    Article  Google Scholar 

  46. Molina-Jijón E, Tapia E, Zazueta C et al (2011) Curcumin prevents Cr(VI)-induced renal oxidant damage by a mitochondrial pathway. Free Radic Biol Med 51:1543–1557

    Article  PubMed  Google Scholar 

  47. Khan S, Vala J, Nabi SU et al (2012) Protective effect of curcumin against arsenic-induced apoptosis in murine splenocytes in vitro. J Immunotoxicol 9:148–159. doi:10.3109/1547691X.2011.637530

    Article  CAS  PubMed  Google Scholar 

  48. Meghana K, Sanjeev G, Ramesh B (2007) Curcumin prevents streptozotocin-induced islet damage by scavenging free radicals: a prophylactic and protective role. Eur J Pharmacol 577:183–191. doi:10.1016/j.ejphar.2007.09.002

    Article  CAS  PubMed  Google Scholar 

  49. Ikezaki S, Nishikawa A, Furukawa F et al (2001) Chemopreventive effects of curcumin on glandular stomach carcinogenesis induced by N-methyl-N’-nitro-N-nitrosoguanidine and sodium chloride in rats. Anticancer Res 21:3407–3411

    CAS  PubMed  Google Scholar 

  50. Sivalingam N, Hanumantharaya R, Faith M et al (2007) Curcumin reduces indomethacin-induced damage in the rat small intestine. J Appl Toxicol 27:551–560. doi:10.1002/jat.1235

    Article  CAS  PubMed  Google Scholar 

  51. Diaz-Mayans J, Laborda R, Nuñez A (1986) Hexavalent chromium effects on motor activity and some metabolic aspects of Wistar albino rats. Comp Biochem Physiol 83:191–195

    CAS  Google Scholar 

  52. Bagchi D, Vuchetich PJ, Bagchi M et al (1997) Induction of oxidative stress by chronic administration of sodium dichromate [chromium VI] and cadmium chloride [cadmium II] to rats. Free Radic Biol Med 22:471–478

    Article  CAS  PubMed  Google Scholar 

  53. Soudani N, Troudi A, Amara IB (2012) Ameliorating effect of selenium on chromium (VI)-induced oxidative damage in the brain of adult rats. J Physiol Biochem 68:397–409. doi:10.1007/s13105-012-0152-4

    Article  CAS  PubMed  Google Scholar 

  54. Magari SR, Schwartz J, Williams PL et al (2002) The association of particulate air metal concentrations with heart rate variability. Environ Health Perspect 110:875–880

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Soudani N, Troudi A, Bouaziz H et al (2011) Cardioprotective effects of selenium on chromium (VI)-induced toxicity in female rats. Ecotoxicol Environ Saf 74:513–520. doi:10.1016/j.ecoenv.2010.06.009

    Article  CAS  PubMed  Google Scholar 

  56. Tsapakos MJ, Hampton TH, Wetterhahn KE (1983) Chromium(VI)-induced DNA lesions and chromium distribution in rat kidney, liver, and lung. Cancer Res 43:5662–5667

    CAS  PubMed  Google Scholar 

  57. Cheng L, Sonntag DM, de Boer J, Dixon K (2000) Chromium(VI)-induced mutagenesis in the lungs of big blue transgenic mice. J Environ Pathol Toxicol Oncol 19:239–249

    CAS  PubMed  Google Scholar 

  58. Chorvatovicova D, Ginter E, Kosinova A, Zloch Z (1991) Effect of vitamins C and E on toxicity and mutagenicity of hexavalent chromium in rat and guinea pig. Mutat Res 262:41–46

    Article  CAS  PubMed  Google Scholar 

  59. Wedeen RP, Qian L (1991) Chromium-induced kidney disease. Environ Health Perspect 92:71–74

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Dartsch PC, Hildenbrand S, Kimmel R, Schmahl FW (1998) Investigations on the nephrotoxicity and hepatotoxicity of trivalent and hexavalent chromium compounds. Int Arch Occup Environ Health 71(Suppl):S40–S45

    PubMed  Google Scholar 

  61. Yam-Canul P, Chirino YI, Sánchez-González DJ et al (2008) Nordihydroguaiaretic acid attenuates potassium dichromate-induced oxidative stress and nephrotoxicity. Food Chem Toxicol 46:1089–1096. doi:10.1016/j.fct.2007.11.003

    Article  CAS  PubMed  Google Scholar 

  62. Parveen K, Khan MR, Siddiqui WA (2009) Pycnogenol prevents potassium dichromate K2Cr2O7-induced oxidative damage and nephrotoxicity in rats. Chem Biol Interact 181:343–350. doi:10.1016/j.cbi.2009.08.001

    Article  CAS  PubMed  Google Scholar 

  63. Khan MR, Siddiqui S, Parveen K et al (2010) Nephroprotective action of tocotrienol-rich fraction (TRF) from palm oil against potassium dichromate (K2Cr2O7)-induced acute renal injury in rats. Chem Biol Interact 186:228–238. doi:10.1016/j.cbi.2010.04.025

    Article  CAS  PubMed  Google Scholar 

  64. Fatima S, Mahmood R (2007) Vitamin C attenuates potassium dichromate-induced nephrotoxicity and alterations in renal brush border membrane enzymes and phosphate transport in rats. Clin Chim Acta 386:94–99. doi:10.1016/j.cca.2007.08.006

    Article  CAS  PubMed  Google Scholar 

  65. Das Neves RP, Santos TM, de Pereira ML, de Jesus JP (2001) Chromium (VI) induced alterations in mouse spleen cells: a short-term assay. Cytobios 106:27–34

    CAS  PubMed  Google Scholar 

  66. Tarasub N, Tarasub C, Na Ayutthaya WD (2008) Effects of quercetin on acute toxicity of rat spleen and chromosome aberrations in bone marrow induced by hexavalent chromium. Thammasat Med J 8:306–316

    Google Scholar 

  67. Trzeciak A, Kowalik J, Małecka-Panas E et al (2000) Genotoxicity of chromium in human gastric mucosa cells and peripheral blood lymphocytes evaluated by the single cell gel electrophoresis (comet assay). Med Sci Monit 6:24–29

    CAS  PubMed  Google Scholar 

  68. Tsao D-A, Tseng W-C, Chang H-R (2011) The expression of RKIP, RhoGDI, galectin, c-Myc and p53 in gastrointestinal system of Cr(VI)-exposed rats. J Appl Toxicol 31:730–740. doi:10.1002/jat.1621

    Article  CAS  PubMed  Google Scholar 

  69. Linos A, Petralias A, Christophi C et al (2011) Oral ingestion of hexavalent chromium through drinking water and cancer mortality in an industrial area of Greece-an ecological study. Environ Heal 10:50

    Article  CAS  Google Scholar 

  70. Gatto N, Kelsh M, Mai D et al (2010) Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: a meta-analysis. Cancer Epidemiol 34:388–399

    Article  CAS  PubMed  Google Scholar 

  71. De Flora S, D’Agostini F, Balansky R et al (2008) Lack of genotoxic effects in hematopoietic and gastrointestinal cells of mice receiving chromium(VI) with the drinking water. Mutat Res 659:60–67. doi:10.1016/j.mrrev.2007.11.005

    Article  PubMed  Google Scholar 

  72. Witt KL, Stout MD, Herbert RA et al (2013) Mechanistic insights from the NTP studies of chromium. Toxicol Pathol 41:326–342. doi:10.1177/0192623312469856

    Article  CAS  PubMed  Google Scholar 

  73. Arivarasu N a, Priyamvada S, Mahmood R (2012) Caffeic acid inhibits chromium(VI)-induced oxidative stress and changes in brush border membrane enzymes in rat intestine. Biol Trace Elem Res 148:209–215. doi:10.1007/s12011-012-9349-1

    Article  CAS  PubMed  Google Scholar 

  74. Arivarasu NA, Fatima S, Mahmood R (2008) Oral administration of potassium dichromate inhibits brush border membrane enzymes and alters anti-oxidant status of rat intestine. Arch Toxicol 82:951–958. doi:10.1007/s00204-008-0311-0

    Article  CAS  PubMed  Google Scholar 

  75. Sengupta T, Chattopadhyay D, Ghosh N et al (1990) Effect of chromium administration on glutathione cycle of rat intestinal epithelial cells. Indian J Exp Biol 28:1132–1135

    CAS  PubMed  Google Scholar 

  76. Upreti RK, Shrivastava R, Chaturvedi UC (2004) Gut microflora & toxic metals: chromium as a model. Indian J Med Res 119:49–59

    CAS  PubMed  Google Scholar 

  77. Shrivastava R, Kannan A, Upreti RK, Chaturvedi UC (2005) Effects of chromium on the resident gut bacteria of rat. Toxicol Mech Methods 15:211–218. doi:10.1080/15376520590945630

    Article  CAS  PubMed  Google Scholar 

  78. Chandra A, Chatterjee A, Ghosh R, Sarkar M (2007) Effect of curcumin on chromium-induced oxidative damage in male reproductive system. Environ Toxicol Pharmacol 24:160–166

    Article  CAS  PubMed  Google Scholar 

  79. Devi KR, Mosheraju M, Reddy KD (2012) Curcumin prevents chromium induced sperm characteristics in mice. IOSR J Pharm 2:312–316

    Google Scholar 

Download references

Acknowledgments

This work was supported by the National Council of Science and Technology (CONACYT no. 220046) and the Project Support Program for Research and Technological Innovation (PAPIIT no. IN210713).

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to José Pedraza-Chaverri.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

García-Niño, W.R., Zatarain-Barrón, Z.L., Hernández-Pando, R. et al. Oxidative Stress Markers and Histological Analysis in Diverse Organs from Rats Treated with a Hepatotoxic Dose of Cr(VI): Effect of Curcumin. Biol Trace Elem Res 167, 130–145 (2015). https://doi.org/10.1007/s12011-015-0283-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-015-0283-x

Keywords

Navigation