Skip to main content
Log in

Exposure to Nickel–Cadmium Contamination of Drinking Water Culminates in Liver Cirrhosis, Renal Azotemia, and Metabolic Stress in Rats

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

Abstract

Drinking water polluted by heavy metals has the potential to expose delicate biological systems to a range of health issues. This study embraced the health risks that may arise from subchronic exposure of thirty-four male Wistar rats to nickel (Ni)-cadmium (Cd)-contaminated water. It was done by using the Box-Behnken design (BBD) with three treatment factors (Ni and Cd doses at 50–150 mg/L and exposure at 14–21-28 days) at a single alpha level, resulting in seventeen experimental combinations. Responses such as serum creatinine (CREA) level, blood urea nitrogen (BUN) level, BUN/CREA ratio (BCR), aspartate and alanine aminotransferases (AST and ALT) activities, and the De Ritis ratio (DRR), as well as malondialdehyde (MDA) level, catalase (CAT), and superoxide dismutase (SOD) activities, were evaluated. The results revealed that these pollutants jointly caused hepatocellular damage by raising AST and ALT activities and renal dysfunction by increasing CREA and BUN levels in Wistar rats’ sera (p < 0.05). These outcomes were further supported by BCR and DRR values beyond 1. In rats’ hepatocytes and renal tissues, synergistic interactions of these metals resulted in higher MDA levels and significant impairments of CAT and SOD activities (p < 0.05). In order to accurately forecast the effects on the responses, the study generated seven acceptable regression models (p < 0.05) with r-squared values of > 80% at no discernible lack of fit (p > 0.05). The findings hereby demonstrated that Wistar rats exposed to these pollutants at varied doses had increased risks of developing liver cirrhosis and azotemia marked by metabolic stress.

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
Fig. 9
Fig. 10

Similar content being viewed by others

Data Availability

Authors are bound to issues of experimental data on rational grounds, but relevant data are already made available in the article and in the supplementary file.

Code Availability

The adoption of design expert software (version 13.0) was affirmed in the study for its experimentation, data analyses, models’ developments, graphical fittings, and critical inferences.

References

  1. WHO (World Health Organization) (2011) Guidelines for drinking-water quality, 4th edn. World Health Organization, Geneva

    Google Scholar 

  2. USEPA (U.S. Environmental Protection Agency) (2015) Regulated drinking water contaminants. http://www.epa.gov/dwstandardsregulations. Accessed Mar 2023

  3. Jamshaid M, Khan AA, Ahmed K, Saleem M (2018) Heavy metal in drinking water its effect on human health and its treatment techniques-a review. Int J Biosci 12(4):223–240. https://doi.org/10.12692/ijb/12.4.223-240

    Article  CAS  Google Scholar 

  4. Nastasescu V, Mititelu M, Goumenou M, Docea OA, Renieri E, Udeanu DI, Oprea E, Arsene AL, Dinu-Pîrvu CE, Ghica M (2020) Heavy metal and pesticide levels in dairy products: evaluation of human health risk. Food Chem Toxicol 146:111844. http://refhub.elsevier.com/S2214-7500(22)00094-4/sbref2. Accessed Feb 2023

  5. Ugwu CE, Maduka IC, Suru SM, Anakwuo IA (2022) Human health risk assessment of heavy metals in drinking water sources in three senatorial districts of Anambra State, Nigeria. Toxicol Reports 9:869–875. https://doi.org/10.1016/j.toxrep.2022.04.011

    Article  CAS  Google Scholar 

  6. World Bank (2016) The World Bank data: country and lending groups. http://data.worldbank.org/about/country-and-lending-groups#Low_income. Accessed Mar 2023

  7. WHO (World Health Organization) (2021) Nickel in drinking-water. Background document for development of WHO Guidelines for drinking-water quality. World Health Organization, Geneva; 2021 (WHO/HEP/ECH/WSH/2021.6). Licence: CC BY-NC-SA 3.0 IGO

  8. Apiamu A, Asagba SO, Tonukari NJ (2019) Role of Anthocleista vogelii in serum antioxidant defence system in cadmium-induced oxidative stress in Wistar rats. Beni-Suef Univ J Basic Appl Sci 8(12):1–13. https://doi.org/10.1186/s43088-019-0012-1

    Article  Google Scholar 

  9. Health Canada (2020) Guidelines for Canadian drinking water quality: Guideline technical document – Cadmium. http://www.canada.ca/en/health-canada/services/environmental-workplace-health/reports-is

  10. ATSDR (Agency for Toxic Substances and Disease Registry) (2005) Toxicological profile for Nickel. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service. http://www.atsdr.cdc.gov/

  11. OEHHA (Office of Environmental Health Hazard Assessment) (2012) Nickel reference exposure levels. Nickel and nickel compounds. Nickel oxide. Reference exposure levels (RELs). https://oehha.ca.gov/media/downloads/crnr/032312nirelfinal.pdf

  12. Bonfim DJP, Garcia FM, Laposy CB, Giuffrida R, Nai GA, Net HB (2021) Influence of water pH in the hepato- and nephrotoxicity of chronic cadmium poisoning in Wistar rats. Res Soc Dev 10(9):e12210917753. https://doi.org/10.33448/rsd-v10i9.17753

    Article  Google Scholar 

  13. Das SC, Al-Naemi HA (2019) Cadmium toxicity: oxidative stress, inflammation and tissue injury. Occup Dis Environ Med 7:144–163. https://doi.org/10.4236/odem.2019.74012

    Article  Google Scholar 

  14. Asagba SO, Eriyamremu GE, Igberaese ME (2008) Bioaccumulation of cadmium and its biochemical effect on selected tissues of the catfish (Clarias gariepinus). Fish Physiol Biochem 34:61–69. https://doi.org/10.1007/s10695-007-9147-4

    Article  PubMed  CAS  Google Scholar 

  15. Cuypers A, Plusquin M, Remans T, Jozefczak M, Keunen E, Gielen H (2010) Cadmium stress: an oxidative challenge. Biometals 23:927–940. https://doi.org/10.1007/s10534-010-9329-x

    Article  PubMed  CAS  Google Scholar 

  16. Genchi G, Sinicropi MS, Lauria G, Carocci A, Catalano A (2020) The effects of cadmium toxicity. Int J Environ Res Public Health 17:3782–3806. https://doi.org/10.3390/ijerph17113782

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Boxton S, Garman E, Heim KE, Lyons-Darden T, Schlekat CE, Taylor MD, Oller AR (2019) Concise review of nickel human health toxicology and ecotoxicology. MDPI Iorg 7:89–127. https://doi.org/10.3390/inorganics7070089

    Article  CAS  Google Scholar 

  18. Das KK, Reddy RC, Bagoji IB, Das S, Bagali S, Mullur L, Khodnapur JP, Biradar MS (2018) Primary concept of nickel toxicity – an overview. J Basic Clin Physiol Pharmacol 1–12. https://doi.org/10.1515/jbscpp-2017-0171

  19. De Brouwere K, Buekers J, Cornelis C, Schlekat CE, Oller AR (2012) Assessment of indirect human exposure to environmental sources of nickel: oral exposure and risk characterization for systemic effects. Sci Total Environ 419:25–36. https://doi.org/10.1016/j.scitotenv.2011.12.049

    Article  ADS  PubMed  CAS  Google Scholar 

  20. IARC (International Agency for Research on Cancer) (2017) IARC monographs on the evaluation of carcinogenic risks to humans: nickel and nickel compounds monograph. WHO Press: Geneva, Switzerland 100C:169–218

    Google Scholar 

  21. EFSA (European Food Safety Agency), (2015) Scientific opinion on the risks to public health related to the presence of nickel in food and drinking water, EFSA Panel on Contaminants in the Food Chain (CONTAM). EFSA J 13:4002

    Google Scholar 

  22. Thyssen JP (2010) Menné T (2010) Metal allergy—a review on exposures, penetration, genetics, prevalence, and clinical implications. Chem Res Toxicol 23:309–318. https://doi.org/10.1021/tx9002726

    Article  PubMed  CAS  Google Scholar 

  23. Saito M, Arakaki R, Yamada A, Tsunematsu T, Kudo Y, Ishimaru N (2016) Molecular mechanisms of nickel allergy. Int J Mol Sci 17:202. https://doi.org/10.3390/ijms17020202

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Das KK, Dasgupta S (2002) Effect of nickel sulfate on testicular steroidogenesis in rats during protein restriction. Environ Health Perspect 110:923–926

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Tikare SN, Gupta AD, Dhundasi SA, Das KK (2008) Effect of antioxidants L-ascorbic acid and alpha-tocopherol supplementation in nickel exposed hyperglycemic rats. J Basic Clin Physiol Pharmacol 19:89–10

    Article  PubMed  CAS  Google Scholar 

  26. Samir D, Zine K (2013) Preventive effect of zinc on nickel-induced oxidative liver injury in rats. Afr J Biotechnol 12(5):7112–7119. https://doi.org/10.5897/AJB2013.12962

    Article  CAS  Google Scholar 

  27. Novelli ELB, Hernandes RT, Novelli-Filho JLVB, Babbosa LL (1998) Differential/combined effect of water contamination with cadmium and nickel on tissues of rats. Environ Pollution 103:295–300

    Article  CAS  Google Scholar 

  28. Apiamu A, Asagba SO (2021) Zinc-cadmium interactions instigated antagonistic alterations in lipid peroxidation, ascorbate peroxidase activity and chlorophyll synthesis in Phaseolus vulgaris leaves. Sci Afr 11:e00688. https://doi.org/10.1016/j.sciaf.2020.e00688

    Article  CAS  Google Scholar 

  29. Said KAM, Amin MAM (2015) Overview on the response surface methodology in extract processes. J Appl Sci Process Eng 2(1):8–17

    Google Scholar 

  30. Apiamu A, Osawaru SU, Asagba SO, Evuen UF, Achuba FI (2021) Exposure of African catfish (Clarias gariepinus) to lead and zinc modulates membrane-bound transport protein: a plausible effect on Na+/K+-ATPase activity. Biol Trace Elem Res. https://doi.org/10.1007/s12011-021-03005-5

    Article  PubMed  Google Scholar 

  31. Asagba SO, Apiamu A, Enokpe FE (2019) Effects of nickel toxicity on the indices of germination and Ca2+ ATPase activity in cowpea plant (Vigna unguiculata). JASEM 23(6):1147–1152

    Article  CAS  Google Scholar 

  32. Lamtai M, Chaibat J, Ouakki S, Berkiks I, Riti E, EI-Hessni A, Mesfioui A, Hbibi AT, Ahyayauch H, Essamri A, Ouichou A (2018) Effect of chronic administration of cadmium on anxiety-like, depression-like and memory deficits in male and female rats: possible involvement of oxidative stress mechanism. J Behav Brain Sci 8: 240-26.https://doi.org/10.4236/jbbs.2018.85016

  33. Reitman S, Frankel S (1957) A colorimetric method for determination of serum glutamate oxaloacetate and glutamic pyruvate transaminase. Am J Clin Pathol 28:56–58

    Article  PubMed  CAS  Google Scholar 

  34. Weatherburn MW (1967) Phenol-hypochlorite reaction for determination of ammonia. Annals Chem 39:971–974

    Article  CAS  Google Scholar 

  35. Prabhakara PV, Reddya UA, Singha SP (2012) Oxidative stress induced by aluminum oxide nanomaterials after acute oral treatment in Wistar rats. J Appli Toxicol 32:436–445

    Article  Google Scholar 

  36. Gavali Y, Deore D, Surwase SP, Zingade U (2013) Study of the serum superoxide dismutase levels in smoking and non-smoking patience with COPD. Int J Recent Trends Sci technol 5:121–126

    Google Scholar 

  37. Ezedom T, Asagba SO, Tonukari NJ (2020) Toxicological effects of the concurrent administration of cadmium and arsenic through the food chain on the liver and kidney of rats. J Basic Appl Zool 81:16–28. https://doi.org/10.1186/s41936-020-00146-2

    Article  Google Scholar 

  38. Singh K (2013) Evaluation and interpretation of biomarkers of liver diseases. Int J Res Health Sci 1(3):213–223

    Google Scholar 

  39. Gao F, Chen C, Lu J, Zheng J, Ma X, Yuan X, Huo K, Ha J (2017) De Ritis ratio (AST/ALT) as an independent predictor of poor outcome in patients with acute ischemic stroke. Neuropsychiatr Dis Treat 13:1551–1557. https://doi.org/10.2147/NDT.S139316

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Apiamu A, Asagba SO, Tonukari NJ (2018) Reporting the toxicological profile of methanolic leaf extract of Anthocleista vogelii planch on Wistar rats. JASEM 22(6):887–894. https://doi.org/10.4314/jasem.v22i6.8

    Article  CAS  Google Scholar 

  41. Lumongga F, Anggraeni R (2016) Correlation between aspartate aminotransferase/alanine transferase ratio (AST/ALT ratio) and stage of liver fibrosis in patients with chronic hepatitis. Adv Health Sci Res 1:72–75

    Google Scholar 

  42. Aberg F, Danford CJ, Thiele M, Talbäck M, Rasmussen DN, Jiang ZG et al (2021) A dynamic aspartate-to-alanine aminotransferase ratio provides valid predictions of incident severe liver disease. Hepatol Comm 5:1021–1035

    Article  Google Scholar 

  43. Griffin BR, Faubel S, Edelstein CL (2019) Biomarkers of drug-induced kidney toxicity. Ther Drug Monit 41(2):213–226. https://doi.org/10.1097/FTD.0000000000000589

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Pócsi I, Dockrell ME, Price RG (2022) Nephrotoxic biomarkers with specific indications for metallic pollutants: implications for environmental health. Biomark Insights 17:1–13. https://doi.org/10.1177/11772719221111882

    Article  Google Scholar 

  45. Suganya R, Priya S, Rajini S, Rajagopalan B (2016) A study to evaluate the role of bun/creatinine ratio as a discriminator factor in azotemia. Int J Pharm Sci Rev Res 40(1):131–134

    CAS  Google Scholar 

  46. Asagba SO, Eriyamremu GE, Emudainohwo JOT, Okoro I (2010) Oxidative enzymes in tissues of the catfish (Clarias gariepinus) exposed to varying levels of cadmium. Environ 30:260–266

    Google Scholar 

  47. Gagné F (2014) Oxidative stress. In: Biochemical ecotoxicology, Elsevier, Amsterdam, 103–115. https://doi.org/10.1016/B978-0-12-411604-7.00006-4

  48. Saleh RM, Awadin WF (2017) Biochemical and histopathological changes of subacute cadmium intoxication in male rats. Environ Sci Pollution Res 24:25475–25481. https://doi.org/10.1007/s11356-017-0348-9

    Article  CAS  Google Scholar 

  49. Ramesh G, Madhuri D, Lakshman M, Reddy AG (2018) Histopathological changes in bone marrow induced by lead and cadmium alone and combined exposure in male Wistar rats. J Entomol Zool St 6:3035–3037

    Google Scholar 

  50. Peijnenburg WJGM, Vijver MG (2007) Metal-specific interactions at the interface of chemistry and biology. Pure Appl Chem 79(12):2351–2366. https://doi.org/10.1351/pac200779122351

    Article  CAS  Google Scholar 

  51. Sauliutė G, Gintaras G (2015) Heavy metal interactions during accumulation via direct route in fish: a review. Zool Ecol 25(1):77–86. https://doi.org/10.1080/21658005.2015.1009734

    Article  Google Scholar 

  52. Kanmani P, Karthik S, Aravind J, Kumaresan K (2013) The use of response surface methodology as a statistical tool for media optimization in lipase production from the dairy effluent isolate Fusarium solani. ISRN Biotechnol 2013:1–8. https://doi.org/10.5402/2013/528708

    Article  CAS  Google Scholar 

  53. Jha P, Das AJ, Deka SC (2018) Optimisation of fermentation process for production of black rice wine and evaluation of its phenolic and volatile compounds. J Inst Brew 124:485–491. https://doi.org/10.1002/jib.504

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This collaborative investigation would not have been possible without the provision of research facilities and enabling environments. Therefore, we are deeply thankful to the departments of respective universities of authors, who contributed immensely to the success of this article.

Author information

Authors and Affiliations

Authors

Contributions

The successful completion of the manuscript was made possible through the notable inputs of the authors: AA, OJA, UFE, HEK, EDK, AAA, GU, and SOA participated in all sections of the study, starting from conceptualization, research design, drafting of proposal, provision of research materials and apparatuses, laboratory investigation, analyses of experimental data, presentation and interpretation of results, drafting and editing of manuscript. Absolute consent by all authors was acknowledged with respect to submission of the manuscript to this journal.

Corresponding author

Correspondence to Augustine Apiamu.

Ethics declarations

Ethics Approval

Sequel to ethics of care and handling of experimental animals, the local research ethics committee gave her approval (REC/FOS/2023/02), in line with international protocols.

Consent to Participate

Not applicable.

Consent for Publication

We affirm that no form of data from individuals or group of persons is associated with the publication of the manuscript.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 34 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Apiamu, A., Avwioroko, O.J., Evuen, U.F. et al. Exposure to Nickel–Cadmium Contamination of Drinking Water Culminates in Liver Cirrhosis, Renal Azotemia, and Metabolic Stress in Rats. Biol Trace Elem Res 202, 1628–1643 (2024). https://doi.org/10.1007/s12011-023-03777-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-023-03777-y

Keywords

Navigation