Skip to main content
Log in

Subchronic Arsenic Exposure Through Drinking Water Alters Vascular Redox Homeostasis and Affects Physical Health in Rats

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

Abstract

We evaluated whether arsenic can alter vascular redox homeostasis and modulate antioxidant status, taking rat thoracic aorta as a model vascular tissue. In addition, we evaluated whether the altered vascular biochemical homeostasis could be associated with alterations in the physical indicators of toxicity development. Rats were exposed to arsenic as 25, 50, and 100 ppm of sodium arsenite through drinking water for 90 consecutive days. Body weight, food intake, and water consumption were recorded weekly. On the 91st day, rats were sacrificed; vital organs and thoracic aorta were collected. Lipid peroxidation, reactive oxygen species generation, and antioxidants were assessed in the thoracic aorta. Arsenic increased aortic lipid peroxidation and hydrogen peroxide generation while decreased reduced glutathione content in a dose-dependent manner. The activities of the enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were decreased. Further, arsenic at 100 ppm decreased feed intake, water consumption, and body weight from the 11th week onward. At this concentration, arsenic increased the relative weights of the liver and kidney. The results suggest that arsenic causes dose-dependent oxidative stress, reduction in antioxidative defense systems, and body weight loss with alteration in hepato-renal organosomatic indices. Overall, subchronic arsenic exposure through drinking water causes alteration in vascular redox homeostasis and at high concentration affects physical health.

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

Similar content being viewed by others

References

  1. Mirza N, Mahmood Q, Maroof Shah M, Pervez A, Sultan S (2014) Plants as useful vectors to reduce environmental toxic arsenic content. Sci World J. doi:10.1155/2014/921581

    Google Scholar 

  2. Jiang JQ, Ashekuzzaman SM, Jiang A, Sharifuzzaman SM, Chowdhury SR (2013) Arsenic contaminated groundwater and its treatment options in Bangladesh. Int J Environ Res Public Health 10:18–46

    Article  PubMed Central  Google Scholar 

  3. WHO (2010) Exposure to arsenic: a major public health concern Geneva: WHO Press. Available: http://www.who.int/ipcs/assessment/public_health/arsenic/en/ [accessed on 23rd October 2013]

  4. Rahaman S, Sinha AC, Pati R, Mukhopadhyay D (2013) Arsenic contamination: a potential hazard to the affected areas of West Bengal, India. Environ Geochem Health 35:119–132

    Article  CAS  PubMed  Google Scholar 

  5. Guha Mazumder D, Dasgupta UB (2011) Chronic arsenic toxicity: studies in West Bengal, India. Kaohsiung J Med Sci 27:360–370

    Article  CAS  PubMed  Google Scholar 

  6. Stea F, Bianchi F, Cori L, Sicari R (2014) Cardiovascular effects of arsenic: clinical and epidemiological findings. Environ Sci Pollut Res Int 21:244–251

    Article  CAS  PubMed  Google Scholar 

  7. Flora SJS (2011) Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 51:257–281

    Article  CAS  PubMed  Google Scholar 

  8. Balakumar P, Kaur J (2009) Arsenic exposure and cardiovascular disorders: an overview. Cardiovasc Toxicol 9:169–176

    Article  CAS  PubMed  Google Scholar 

  9. Lynn S, Gurr JR, Lai HT, Jan KY (2000) NADH oxidase activation is involved in arsenite-induced oxidative DNA damage in human vascular smooth muscle cells. Circ Res 86:514–519

    Article  CAS  PubMed  Google Scholar 

  10. Barchowsky A, Klei LR, Dudek EJ, Swartz HM, James PE (1999) Stimulation of reactive oxygen, but not reactive nitrogen species, in vascular endothelial cells exposed to low levels of arsenite. Free Radic Biol Med 27:1405–1412

    Article  CAS  PubMed  Google Scholar 

  11. Simeonova PP, Luster MI (2004) Arsenic and atherosclerosis. Toxicol Appl Pharmacol 198:444–449

    Article  CAS  PubMed  Google Scholar 

  12. Sharma B, Sharma PM (2013) Arsenic toxicity induced endothelial dysfunction and dementia: pharmacological interdiction by histone deacetylase and inducible nitric oxide synthase inhibitors. Toxicol Appl Pharmacol 273:180–188

    Article  CAS  PubMed  Google Scholar 

  13. Yang HT, Chou HJ, Han BC, Huang SY (2007) Lifelong inorganic arsenic compounds consumption affected blood pressure in rats. Food Chem Toxicol 45:2479–2487

    Article  CAS  PubMed  Google Scholar 

  14. Ford RJ, Graham DA, Denniss SG, Quadrilatero J, Rush JWE (2006) Glutathione depletion in vivo enhances contraction and attenuates endothelium-dependent relaxation of isolated rat aorta. Free Radic Biol Med 40:670–678

    Article  CAS  PubMed  Google Scholar 

  15. Paula FB, Gouvea CM, Alfredo PP, Salgado I (2005) Protective action of a hexane crude extract of Pterodon emarginatus fruits against oxidative and nitrosative stress induced by acute exercise in rats. BMC Compliment Alternat Med 5:17–25

    Article  Google Scholar 

  16. Madesh M, Balasubramanian KA (1998) Microtiter plate assay for superoxide dismutase using MTT reduction by superoxide. Indian J Biochem Biophys 35:84–188

    Google Scholar 

  17. Aebi HE (1983) Catalase. In: Bergmeyer HU, Bergmeyer J, Grabi M (Eds.) Methods of enzymatic analysis, third ed., vol. III. Verlag Chemie, Weinheim, pp. 273–286

  18. Goldberg DM, Spooner RJ (1983) Glutathione reductase. In: Bergmeyer HU, Bergmeyer J, Grabi M (eds) Methods of enzymatic analysis, vol III. Verlag Chemie, Weinheim, pp 258–265

    Google Scholar 

  19. Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound and nonprotein bound sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205

    Article  CAS  PubMed  Google Scholar 

  20. Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    CAS  PubMed  Google Scholar 

  21. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  22. Muthumani M (2013) Tetrahydrocurcumin potentially attenuates arsenic induced oxidative hepatic dysfunction in rats. J Clin Toxicol. doi:10.4172/2161-0495.1000168

    Google Scholar 

  23. Touyz RM, Schiffrin EL (2008) Reactive oxygen species and hypertension: a complex association. Antioxid Redox Signal 10:1041–1044

    Article  CAS  PubMed  Google Scholar 

  24. Lee SE, Park YS (2013) Role of lipid peroxidation-derived α, β unsaturated aldehydes in vascular dysfunction. Oxid Med Cell Longev. doi:10.1155/2013/629028

    Google Scholar 

  25. Hossain E, Ota A, Takahashi M, Karnan S, Damdindorj L, Konishi Y, Konishi H, Hosokawa Y (2013) Arsenic upregulates the expression of angiotensin II Type I receptor in mouse aortic endothelial cells. Toxicol Lett 220:70–75

    Article  CAS  PubMed  Google Scholar 

  26. Kesavan M, Sarath TS, Kannan K, Suresh S, Gupta P, Vijayakaran K, Sankar P, Kurade NP, Mishra SK, Sarkar SN (2014) Atorvastatin restores arsenic-induced vascular dysfunction in rats: modulation of nitric oxide signaling and inflammatory mediators. Toxicol Appl Pharmacol 280:107–116

  27. Lee PC, Ho IC, Lee TC (2005) Oxidative stress mediates sodium arsenite-induced expression of heme oxygenase-1, monocyte chemoattractant protein-1, and interleukin-6 in vascular smooth muscle cells. Toxicol Sci 85:541–550

    Article  CAS  PubMed  Google Scholar 

  28. De Vizcaya-Ruiz A, Barbier O, Ruiz-Ramos R, Cebrian ME (2009) Biomarkers of oxidative stress and damage in human populations exposed to arsenic. Mutat Res 674:85–92

    Article  PubMed  Google Scholar 

  29. Masella R, Di Benedetto R, Varì R, Filesi C, Giovannini C (2005) Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. J Nutr Biochem 16:577–586

    Article  CAS  PubMed  Google Scholar 

  30. Radabaugh TR, Aposhian HV (2000) Enzymatic reduction of arsenic compounds in mammalian system: reduction of arsenate to arsenite by human liver arsenate reductase. Chem Res Toxicol 13:26–30

    Article  CAS  PubMed  Google Scholar 

  31. Bhattacharya S, Bhattacharya A, Roy S (2007) Arsenic-induced responses in freshwater teleosts. Fish Physiol Biochem 33:463–473

    Article  CAS  Google Scholar 

  32. Gregus Z (2008) Mechanism of toxicity. In: Casarett and Doull’s toxicology: the basic science of poisons. Klaassen CD (Ed.), 7th ed., McGraw-Hill, New York, pp 45-106

  33. Sinet PM, Garber P (1981) Inactivation of human Cu-Zn superoxide dismutase during exposure to O2 ●– and H2O2. Arch Biochem Biophys 212:411–416

    Article  CAS  PubMed  Google Scholar 

  34. Kono Y, Fridovich I (1982) Superoxide radical inhibits catalase. J Biol Chem 257:5751–5754

    CAS  PubMed  Google Scholar 

  35. Shila S, Kokilavani V, Subathra M, Panneerselvam C (2005) Brain regional responses in antioxidant system to alpha-lipoic acid in arsenic intoxicated rat. Toxicol 210:25–36

    Article  CAS  Google Scholar 

  36. Paul DS, Hernandez-Zavala A, Walton FS, Adair BM, Dedina J, Matousek T, Styblo M (2007) Examination of the effects of arsenic on glucose a mouse model for arsenic-induced diabetes. Toxicol Appl Pharmacol 222:305–314

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Lu TH, Su CC, Chen YW, Yang CY, Wu CC, Hung DZ, Chen CH, Cheng PW, Liu SH, Huang CF (2011) Arsenic induces pancreatic β-cell apoptosis via the oxidative stress-regulated mitochondria-dependent and endoplasmic reticulum stress-triggered signaling pathways. Toxicol Lett 201:15–26

    Article  CAS  PubMed  Google Scholar 

  38. Naujokas MF, Anderson B, Ahsan H, Aposhian HV, Graziano JH, Thompson C, Suk WA (2013) The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem. Environ Health Perspect 121:295–302

    Article  PubMed Central  PubMed  Google Scholar 

  39. Flora SJ (1999) Arsenic-induced oxidative stress and its reversibility following combined administration of N-acetylcysteine and meso 2,3-dimercaptosuccinic acid in rats. Clin Exp Pharmacol Physiol 26:865–869

    Article  CAS  PubMed  Google Scholar 

  40. Ramanathan K, Balakumar BS, Panneerselvam C (2002) Effects of ascorbic acid and α-tocopherol on arsenic-induced oxidative stress. Hum Exp Toxicol 21:675–680

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to the Department of Biotechnology (DBT), New Delhi, India, for providing financial support in conducting the study. The fellowship awarded to the first author by the institute is gratefully acknowledged. The authors are also thankful to the Director of Indian Veterinary Research Institute for providing necessary facilities.

Conflict of Interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Souvendra Nath Sarkar.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Waghe, P., Sarath, T.S., Gupta, P. et al. Subchronic Arsenic Exposure Through Drinking Water Alters Vascular Redox Homeostasis and Affects Physical Health in Rats. Biol Trace Elem Res 162, 234–241 (2014). https://doi.org/10.1007/s12011-014-0116-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-0116-3

Keywords

Navigation