Environmental Science and Pollution Research

, Volume 25, Issue 26, pp 26383–26393 | Cite as

Intraperitoneal sodium metavanadate exposure induced severe clinicopathological alterations, hepato-renal toxicity and cytogenotoxicity in African giant rats (Cricetomys gambianus, Waterhouse, 1840)

  • Ifukibot Levi Usende
  • Chibuisi G. Alimba
  • Benjamin O Emikpe
  • Adekunle A. Bakare
  • James Olukayode Olopade
Research Article


Pollution of environment due to increased exploitation of minerals has been on the rise, and vanadium, a metal in the first transition series essential for mammalian existence, is a major component of air pollution. This study investigated the clinico-pathological, hepato-renal toxicity, and cytogenotoxicity of intraperitoneal exposure of African giant rats (AGRs), a proposed model for ecotoxicological research to sodium metavanadate. A total of 27 adult male African giant rats weighing 975 ± 54.10 g were distributed into two major groups: sodium metavanadate (SMV) treated and control. They were observed daily for clinical signs of toxicity. Four rats from each group were randomly collected and sacrificed after 3, 7, and 14 days of SMV treatment. Liver, kidney, and bone marrow were analyzed for histopathology and micronucleated normochromated and polychromated erythrocytes (MNNCE and MNPCE), respectively. Clinical signs in treated AGR include sluggish and weak movements, un-groomed fur, and labored breathing. Histology of the kidney revealed severe glomerular atrophy, tubular ectasia, and vacuolar degeneration of tubular epithelium, while liver histology showed sinusoidal congestion and severe hepatocellular necrosis after 14 days SMV exposure. Also, MNNCE and MNPCE significantly increased with a decrease in PCE/NCE ratio in SMV-treated AGR, suggestive of alternations in bone marrow cell proliferation. Hence, SMV treatment to AGR resulted to severe clinicopathologic alterations, kidney, and liver dysfunction and cytogenotoxicity evident by somatic mutation induction which could be severe with prolonged exposure. This suggests African giant rat as an ecotoxicological model to measure major health risks to animals and human populations in highly polluted environment.


African giant rats Sodium metavanadate Ecotoxicological model Genotoxicity Micronucleus assay 


  1. Adeoye GO, Alimba CG, Oyeleke OB (2015) The genotoxicity and systemic toxicity of a pharmaceutical effluent in Wistar rats may involve oxidative stress induction. Toxicol Rep 2:1265–1272CrossRefGoogle Scholar
  2. Alimba CG, Bakare AA (2016) In vivo micronucleus test in the assessment of cytogenotoxicity of landfill leachates in three animal models from various ecological habitats. Ecotoxicology 25(2):310–319CrossRefGoogle Scholar
  3. Altamirano M, Ayala ME, Flores A, Morales L, Dominguez R (1991) Sex differences in the effects of vanadium pentoxide administration to prepubertal rats. Med Sci Res 19:825–826Google Scholar
  4. Altamirano-Lozano MA, Alvarez-Barrera L, Basurto-Alcántara F, Valverde M, Rojas E (1996) Reprotoxic and genotoxic studies of vanadium pentoxide in male mice. Teratog Carcinog Mutagen 16:7–17CrossRefGoogle Scholar
  5. Altamirano-Lozano MA, Roldan-Reyes E, Rojas E (1998) Genetic toxicology of vanadium compounds. In: Nriagu JO (ed) Vanadium in the Environment. Part 2: Health Effects. John Wiley and Sons, New YorkGoogle Scholar
  6. Altamirano-Lozano M, Valverde M, Alvarez-Barrera L, Molina B, Rojas E (1999) Genotoxic studies of vanadium pentoxide (V2O5) in male mice. II. Effects in several mouse tissues. Teratog Carcinog Mutagen 19:243–255CrossRefGoogle Scholar
  7. Amacher DE, Schomaker SJ, Boldt SE, Mirsky M (2006) The relationship amongmicrosomal enzyme induction, liver weight and histological change in Cynomolagus monkey toxicology studies. Food Chem Toxicol 44:528–537CrossRefGoogle Scholar
  8. Attia SM, Badary OA, Hamada FM, de Angelis MH, Adler ID (2005) Ortho-vanadate increased the frequency of aneuploid mouse sperm without micronucleus induction in mouse bone marrow erythrocytes at the same dose level. Mutat Res 583:158–167CrossRefGoogle Scholar
  9. Barceloux DG (1999) Vanadium. J Toxicol Clin Toxicol 37:265–278CrossRefGoogle Scholar
  10. Bay B, Sith K, Paramanamtham R, Chan Y (1997) Hydroxyl free radicals generated by vanadyl (IV) induce cell blebbing in mitotic human Chang liver cells. Biometals 10:119–122CrossRefGoogle Scholar
  11. Calderon-Garciduenas L, Maronpot RR, Torres-Jardon R, Henriquez-Roldan C, Schoonhoven R, Acuna-Ayala H, Villlarreal-Calderon A, Nakamura J, Fernando R, Reed W, Azzarelli B, Swenberg JA (2003) DNA damage in nasal and brain tissues of canines exposed to air pollution is associated with evidence of chronic brain inflammation and neurodegeneration. Toxicol Pathol 31:524–538CrossRefGoogle Scholar
  12. Ciranni R, Antonetti M, Migliore L (1995) Vanadium salts induce cytogenetic effects in vivo treated mice. Mutat Res 343:53–60CrossRefGoogle Scholar
  13. Garcia GB, Quiroga AD, Sturtz N, Martinez AI, Biancardi ME (2004) Morphological alterations of central nervous system (CNS) meylin in vanadium (V)-exposed adult rats. Drug Chem Toxicol 27:281–293CrossRefGoogle Scholar
  14. Garcia GB, Biancardi ME, Quiroga AD (2005) Vanadium (V)-induced neurotoxicity in the rat central nervous system: a histo-immunohistochemical study. Drug Chem Toxicol 27:281–293CrossRefGoogle Scholar
  15. Ghio AJ, Silbajoris R, Carson JL, Samet JM (2002) Biologic effects of oil fly ash. Environ Health Perspect 110:89–94CrossRefGoogle Scholar
  16. Haider SS, Abdel-Gayoum AA, El-Fakhri M, Ghwarsha KM (1998) Effect of selenium on vanadium toxicity in different regions of rat brain. Hum Exp Toxicol 17:23–28CrossRefGoogle Scholar
  17. Halliwell B, Gutteridge JM (1990) Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol 186:1–85CrossRefGoogle Scholar
  18. Ibe CS, Onyeansusi BI, Hambolu JO (2014) Functional morphology of the brain of the African giant pouched rat (Cricetomysgambianus; Waterhouse, 1840). Onderstepoort J Vet Res 81(1):1–7CrossRefGoogle Scholar
  19. Igado OO, Olopade JO, Onwuka SK, Chukwudi AC, Daramola OA, Ajufo UE (2008) Evidence of environmental pollution in caprine brains obtained from a relatively unindustrialized area in Nigeria. Afr J Biomed Res 11:305–309Google Scholar
  20. Ivancsits S, Pilger A, Diem E, SchaVer A, Rudiger HW (2002) Vanadate induces DNA strand breaks in cultured human fibroblasts at doses relevant to occupational exposure. Mutat Res 519:25–35CrossRefGoogle Scholar
  21. Krishna G, Hayashi M (2000) In vivo rodent micronucleus assay: protocol, conduct and data interpretation. Mutat Res 455:155–166CrossRefGoogle Scholar
  22. Leonard A, Gerber GB (1994) Mutagenicity, carcinogenicity and teratogenicity of vanadium compounds. Mutat Res 317:81–88CrossRefGoogle Scholar
  23. Leopardi P, Villani P, Cordelli E, Siniscalchi E, Veschetti E, Crebelli R (2005) Assessment of the in vivo genotoxicity of vanadate: analysis of micronuclei and DNA damage induced in mice by oral exposure. Toxicol Lett 158:39–49CrossRefGoogle Scholar
  24. Liu Y, Chen DD, Xing YH, Ge N, Zhang Y, Liu J, Zou W (2014) A new oxovanadium complex enhances renal function by improving insulin signaling pathway in diabetic mice. J Diabetes Complicat 28:265–272CrossRefGoogle Scholar
  25. Luiz CJ, Jose C (2005) Basic histology: text and atlas. McGraw Hill Books Co, New YorkGoogle Scholar
  26. Mailhes JB, Hilliard C, Fuseler JW, London SN (2003) Vanadate, an inhibitor of tyrosine phosphatases, induced premature anaphase in oocytes and aneuploidy and polyploidy in mouse bone marrow cells. Mutat Res 538:101–107CrossRefGoogle Scholar
  27. Marouane W, Soussi A, Murat JC, Bezzine S, El Feki A (2011) The protective effect of Malva sylvestris on rat kidney damaged by vanadium. Lipids Health Dis 10:65CrossRefGoogle Scholar
  28. Migliore L, Bocciardi R, Macri C, Lo Jacono F (1993) Cytogenetic damage induced in human lymphocytes by four vanadium compounds and micronucleus analysis by fluorescence in situ hybridization with a centromeric probe. Mutat Res 319:205–213CrossRefGoogle Scholar
  29. Migliore L, Scarpato R, Falco P (1995) The use of fluorescence in situ hybridization with a -satellite DNA probe for the detection of acrocentric chromosomes in vanadium-induced micronuclei. Cytogenet Cell Genet 69:215–219CrossRefGoogle Scholar
  30. Morinville A, Maysinger D, Shaver A (1998) From vanadis to atropos: vanadium compounds as pharmacological tools in cell death signalling. Trends Pharmacol Sci 19:452–460CrossRefGoogle Scholar
  31. Morita T, Asano N, Awogi T, Sasaki YF, Sato S, Shimada H, Sutou S, Suzuli T, Wakata A, Sofuni T, Hayashi M (1997) Evaluation of the rodent micronucleus assay in the screening of IARC carcinogens (Group 1. 2A and 2B). The summary report of the 6th collaborative study by CSGMT/ JEMS MMS. Mutat Res 389:3–122CrossRefGoogle Scholar
  32. Olaolorun FA, Obasa AA, Balogun HA, Aina OO, Olopade JO (2014) Lactational vitamin E protects against the histotoxic effects of systemically administered vanadium in neonatal rats. Niger J Physiol Sci 29:125–129Google Scholar
  33. Olopade JO, Connor JR (2011) Vanadium and neurotoxicity: a review. Curr Top Toxicol 7:33–39Google Scholar
  34. Olopade JO, Onwuka SK, Adejumo D, Ladokun AA (2005) Analysis of some industrial metals and ions in the cerebral cortex of goats in Nigeria. Niger Vet J 26(2):51–55Google Scholar
  35. Paola V, Eugenia C, Paola L, Ester S, Enrico V, Anna MF, Riccardo C (2007) Evaluation of genotoxicity of oral exposure to tetravalent vanadium in vivo. Toxicol Lett 170(1):11–18CrossRefGoogle Scholar
  36. PUBLIC HEALTH SERVICE (1996) Public Health Service Policy on Humane Care and the Use of Lab Anim. US Department of Health and Humane Services, Washington DCGoogle Scholar
  37. Rodrıguez-Mercado JJ, Elia R, Altamirano-Lozano M (2003) Genotoxic effects of vanadium(IV) in human peripheral blood cells. Toxicol Lett 144:359–369CrossRefGoogle Scholar
  38. Rodriguez-Mercado JJ, Rodrigo AM, Altamirano-Lozano M (2011) DNA damage induction in human cells exposed to vanadium oxides in vitro. Toxicol in Vitro 25:1996–2002CrossRefGoogle Scholar
  39. Rojas E, Valverde M, Herrera LA, Altamirano-Lozano M, Ostrosky-Wegman P (1996) Genotoxicity of vanadium pentoxide evaluate by the single cell gel electrophoresis assay in human lymphocytes. Mutat Res 359:77–84CrossRefGoogle Scholar
  40. Rojas-Lemus M, Altamirano-Lozano M, Fortoul TI (2014) Sex differences in blood genotoxic and cytotoxic effects as a consequence of vanadium inhalation: micronucleus assay evaluation. J Appl Toxicol 34(3):258–264Google Scholar
  41. Roldan E, Altamirano M (1990) Chromosomal aberrations, sister chromatid exchanges, cell-cycle kinetics and satellite association in human lymphocytes cultures exposed to vanadium pentoxide. Mutat Res 245(2):61–65CrossRefGoogle Scholar
  42. Sarsebekov EK, Dzharbusynov BU, Doskeeva RA (1994) The nephrotoxic action of heavy crude with a high vanadium content and of its refinery products. Urol Nefrol (Mosk) 3:35–36Google Scholar
  43. Schmid W (1975) The micronucleus test. Mutat Res 31:9–15CrossRefGoogle Scholar
  44. Scibior A, Zaporowska H, Banach A (2006) Combined effect of vanadium (V) and chromium(III) on lipid peroxidation in liver and kidney of rats. Chem Biol Interact 159:213–222CrossRefGoogle Scholar
  45. Shi X, Dalal NS (1992) Hydroxyl radical generation in the NADH/microsomal reduction of vanadate. Free Radic Res Commun 17:369–376CrossRefGoogle Scholar
  46. Shi X, Jiang H, Mao Y, Ye J, Sayotti U (1996) Vanadium(IV)-mediated free radical generation and related 2-deoxyguanosine hydroxylation and DNA damage. Toxicology 106:27–38CrossRefGoogle Scholar
  47. Shrivastava S, Jado A, Shukla S (2007) Effect of Tiron and its combination with nutritional supplements against vanadium intoxication in female albino rats. J Toxicol Sci 32:185–192CrossRefGoogle Scholar
  48. Sit KH, Paramanantham R, Bay BH, Chan HL, Wong KP, Thong P, Watt F (1996) Sequestration of mitotic (M-phase) chromosomes in autophagosomes: mitotic programmed cell death in human chang liver cells induced by an OH• burst from vanadyl(4). Anat Rec 245:1–8CrossRefGoogle Scholar
  49. Stalker MJ, Hayes MA (2007) Liver and biliary system. In: Maxie MG (ed) Jubb, Kennedy and Palmer’s pathology of domestic animals, 5th edn. Elsevier, Edinburgh, p 320Google Scholar
  50. Syed ZHS, Abdul Khaliq N, Amir R (2016) Neprotoxicity by oral vanadyl sulphate in rats. PAFM 66(3):386–389Google Scholar
  51. Todorich B, Olopade JO, Surguladze N, Zhang X, Neely E, Connor J (2011) The mechanism of vanadium-mediated developmental hypomyelination is related to destruction of oligodendrocyte progeinitors through a relationship with ferritin and iron. Neurotox Res 19:361–373CrossRefGoogle Scholar
  52. Tracey AS, Willsky GR, Takeuchi ES (2007) Vanadium: chemistry, biochemistry, pharmacology and practical applications. CRC Press, Florida, p 250Google Scholar
  53. Usende IL, Leitner DF, Neely E, Connor JR, Olopade JO (2016) The deterioration seen in myelin related morpho-physiology in vanadium exposed rats is partially protected by concurrent iron deficiency. Niger J Physiol Sci 31(1):11–22Google Scholar
  54. Usende IL, Emikpe BO, Olopade JO (2017) Heavy metal pollutants in selected organs of African giant rats from three agro-ecological zones of Nigeria: evidence for their role as an environmental specimen Bank. Environ Sci Pollut Res 24:22570–22578CrossRefGoogle Scholar
  55. Usende IL, Oyagbemi AA, Emikpe BO, Adedapo A, Olopade JO (2018) Oxidative stress changes observed in selected organs of African giant rats (Cricetomys gambianus) exposed to sodium metavanadate. IJVSM 6:80–89Google Scholar
  56. Vallejo M, Jáuregui-Renaud K, Hermosillo AG, Márquez MF, Cárdenas M (2003) Efectos de la contaminaciónatmosféricaen la salud y suimportanciaen la ciudad de México. Gac Med Mex 139:57–63Google Scholar
  57. Wozniak K, Blasiak Y (2004) Vanadyl sulphate can differentially damage DNA in human lymphocytes and HeLa cells. Arch Toxicol 78:7–15CrossRefGoogle Scholar
  58. Yamamoto KI, Kikuchi Y (1981) Studies on micronuclei time response and on the effects of multiple treatments of mutagens on induction of micronuclei. Mutat Res 90:163–173CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Veterinary AnatomyUniversity of AbujaAbujaNigeria
  2. 2.Department of Veterinary AnatomyUniversity of IbadanIbadanNigeria
  3. 3.Department of ZoologyUniversity of IbadanIbadanNigeria
  4. 4.Department of Veterinary PathologyUniversity of IbadanIbadanNigeria

Personalised recommendations