Skip to main content

Advertisement

Log in

Ochratoxin A and citrinin nephrotoxicity in New Zealand White rabbits: an ultrastructural assessment

  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

In the present investigation, ochratoxin A (OTA) (0.75 mg/kg feed) and citrinin (CIT) (15 mg/kg feed) were fed alone and in combination to young growing New Zealand White rabbits for 60 days to evaluate renal ultrastructural alterations. The severity and intensity of renal ultrastructural changes varied with the type of the treatment, and predominant and consistent lesions were recorded in the proximal convoluted tubule (PCT) lining cells. The significant changes in mitochondria, the most affected cell organelle in all the treatment groups, included mitochondrial disintegration and distortion, pleomorphism, cluster formation and misshapen appearance such as signet ring, dumbbell, cup and U shapes. Intra-cisternal sequestrations of involuting mitochondria, and thickening of basal layer of PCT epithelial cells with partial detachment, were the characteristic features observed in OTA and combination treatments. CIT treatment revealed crenated nucleus, loss of nucleolus, depletion of cytoplasmic organelles, mitochondrial pleomorphism, nuclear fragmentation, uniform folding of cell membrane and cytoplasmic vacuolations in the PCTs. Focal thickening of the glomerular basement membrane and degeneration of endothelial cells were the prominent alterations in the glomeruli in OTA and combination treatments. Distal convoluted tubules were unaffected in CIT treatment, however, mild to moderate lesions were observed in OTA and combination treated rabbits. It may be concluded that on simultaneous exposure, CIT potentiated the toxic effects of OTA on renal ultrastructure.

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.

Similar content being viewed by others

Abbreviations

BM:

basement membrane

CIT:

citrinin

DCT:

distal convoluted tubule

FP:

foot processes of podocytes

ICS:

intra-cisternal sequestration

IS:

interstitial space

Lu:

lumen

M:

mitochondria

Mv:

microvilli

N:

nucleus

OTA:

ochratoxin A

PCT:

proximal convoluted tubule

RER:

rough endoplasmic reticulum

US :

urinary space

References

  1. N Magan (2006) ArticleTitleMycotoxin contamination of food in Europe: Early detection and prevention strategies Mycopathologia 162 IssueID3 245–253 10.1007/s11046-006-0057-2 Occurrence Handle10.1007/s11046-006-0057-2 Occurrence Handle1:CAS:528:DC%2BD28XptVegsrg%3D Occurrence Handle16944291

    Article  CAS  PubMed  Google Scholar 

  2. P Krogh B Hald EJ Pedersen (1973) ArticleTitleOccurrence of ochratoxin A and citrinin in cereals associated with porcine nephropathy Acta Pathol Microbiol Scand 81 689–695 Occurrence Handle1:CAS:528:DyaE2cXktlChsL0%3D

    CAS  Google Scholar 

  3. P Bayman JL Baker (2006) ArticleTitleOchratoxins: A global perspective Mycopathologia 162 IssueID3 215–223 10.1007/s11046-006-0055-4 Occurrence Handle10.1007/s11046-006-0055-4 Occurrence Handle1:CAS:528:DC%2BD28XptVegsro%3D Occurrence Handle16944288

    Article  CAS  PubMed  Google Scholar 

  4. NAQ Mehdi WW Carlton (1981) ArticleTitleCitrinin mycotoxicosis in broiler chickens Food Cosmet Toxicol 19 723–733 10.1016/0015-6264(81)90527-7 Occurrence Handle10.1016/0015-6264(81)90527-7 Occurrence Handle1:CAS:528:DyaL38XhslGksbo%3D Occurrence Handle7327473

    Article  CAS  PubMed  Google Scholar 

  5. Krogh P, Nesheim S, Ochratoxin A In: Stolloff L, Castegnaro M, Scott P, O’Neill IK, Bartsch H, eds., Environment carcinogens: Selected method for analysis, Vol. 5. Some mycotoxins. International Agency for Research on Cancer, Lyon, 1982: 247–253

  6. A Pfohl-Leszkowicz T Petkova-Bocharova IN. M Chernozemsky Castegnaro (2002) ArticleTitleBalkan endemic nephropathy and associated urinary tract tumors: a review on aetiological causes and the potential role of mycotoxins Food Addit Contam 19 IssueID3 282–302 10.1080/02652030110079815 Occurrence Handle10.1080/02652030110079815 Occurrence Handle1:CAS:528:DC%2BD38Xis1Wqs7c%3D Occurrence Handle11834078

    Article  CAS  PubMed  Google Scholar 

  7. MS Mir P Dwivedi K Charan (1999) ArticleTitleOchratoxin A induced acute toxicity in rabbits Indian J Vet Pathol 23 IssueID1–2 8–13

    Google Scholar 

  8. C Hanika WW Carlton (1994) Toxicology and pathology of citrinin GC Llewellyn WV Dashek CE O’Rear (Eds) Biodeterioriation Research NumberInSeriesVol. 4 Plenum Press New York 41–63

    Google Scholar 

  9. K Kpodo AK Serensenb M Jakobsen (1996) ArticleTitleThe occurrence of mycotoxins in fermented maize products Food Chem 56 IssueID2 147–153 10.1016/0308-8146(95)00155-7 Occurrence Handle10.1016/0308-8146(95)00155-7 Occurrence Handle1:CAS:528:DyaK28XjvFCrtr8%3D

    Article  CAS  Google Scholar 

  10. NH Aziz A Loutfy A Moussa (2002) ArticleTitleInfluence of gamma-radiation on mycotoxin producing moulds and mycotoxins in fruits Food Control 13 281–288 10.1016/S0956-7135(02)00028-2 Occurrence Handle10.1016/S0956-7135(02)00028-2 Occurrence Handle1:CAS:528:DC%2BD38XjvVeltr8%3D

    Article  CAS  Google Scholar 

  11. A Manickam A Palaniswami S Neelakantan (1985) ArticleTitleMycotoxicosis in buffaloes Indian Vet J 62 IssueID8 711–714

    Google Scholar 

  12. T Vrabcheva E Usleber R Dietrich E Martlbauer (2000) ArticleTitleCo-occurrence of ochratoxin A and citrinin in cereals from Bulgarian villages with a history of Balkan endemic nephropathy J Agric Food Chem 48 IssueID6 2483–2488 10.1021/jf990891y Occurrence Handle10.1021/jf990891y Occurrence Handle1:CAS:528:DC%2BD3cXjtlygtL4%3D Occurrence Handle10888572

    Article  CAS  PubMed  Google Scholar 

  13. EK Tangni L Pussemier (2006) ArticleTitleOchratoxin A and citrinin loads in stored wheat grains: Impact of grain dust and possible prediction using ergosterol measurement Food Addit Contam 23 IssueID2 181–189 10.1080/02652030500391911 Occurrence Handle10.1080/02652030500391911 Occurrence Handle1:CAS:528:DC%2BD28XhtVeiurg%3D Occurrence Handle16449061

    Article  CAS  PubMed  Google Scholar 

  14. GA Sansing EB Lillehoj RW Detroy (1976) ArticleTitleSynergistic toxic effect of citrinin, ochratoxin A and penicillic acid in mice Toxicon 14 213–220 10.1016/0041-0101(76)90009-X Occurrence Handle10.1016/0041-0101(76)90009-X Occurrence Handle1:CAS:528:DyaE28Xksleiu78%3D Occurrence Handle941175

    Article  CAS  PubMed  Google Scholar 

  15. HL Trenk ME Butz FS Chu (1971) ArticleTitleProduction of ochratoxin in different cereal products by Aspergillus ochraceus Appl Microbiol 21 1032–1035 Occurrence Handle1:CAS:528:DyaE3MXksVGkuro%3D Occurrence Handle5564676

    CAS  PubMed  Google Scholar 

  16. AOAC Official method of analysis, 16th edn. Washington, DC: AOAC International. 1995; Vol. 49: 40-1

  17. LK Jackson A Ciegler (1978) ArticleTitleProduction and analysis of citrinin in corn Appl Environ Microbiol 36 IssueID3 408–411 Occurrence Handle1:CAS:528:DyaE1cXlslKmsLs%3D Occurrence Handle727774

    CAS  PubMed  Google Scholar 

  18. ES Reynolds (1963) ArticleTitleThe use of lead citrate at high pH as an electron opaque stain in electron microscopy J Cell Biol 17 208–212 10.1083/jcb.17.1.208 Occurrence Handle10.1083/jcb.17.1.208 Occurrence Handle1:CAS:528:DyaF3sXktVClu70%3D Occurrence Handle13986422

    Article  CAS  PubMed  Google Scholar 

  19. P Dwivedi RB Burns MH Maxwell (1984) ArticleTitleUltrastructural study of the liver and kidney in ochratoxicosis A in young broiler chicks Res Vet Sci 36 104–116 Occurrence Handle1:STN:280:DyaL2c7ntFektQ%3D%3D Occurrence Handle6709970

    CAS  PubMed  Google Scholar 

  20. F Elling (1981) Ochratoxin A induced Porcine Nephropathy: Structural Changes and Pathogenesis DSR Forlag Copenhagen 1–32

    Google Scholar 

  21. CC Satheesh AK Sharma K Prasanna P Dwivedi (2004) ArticleTitleUltrastructural changes in kidneys and liver in experimentally induced ochratoxicosis in Wistar rats Indian J Vet Pathol 28 IssueID1 21–24

    Google Scholar 

  22. H Meisner S Chan (1974) ArticleTitleOchratoxin A, an inhibitor of mitochondrial transport system Biochem New York 13 2795–2799 10.1021/bi00711a002 Occurrence Handle10.1021/bi00711a002 Occurrence Handle1:CAS:528:DyaE2MXjvFalug%3D%3D

    Article  CAS  Google Scholar 

  23. D Hoehler RR Marquardt AR Mclintosh GM Hatch (1997) ArticleTitleInduction of free radicals in hepatocytes, mitochondria and microsomes of rat by ochratoxin-A and its analogues Biochem Biophys Acta 1357 225–233 10.1016/S0167-4889(97)00026-8 Occurrence Handle10.1016/S0167-4889(97)00026-8 Occurrence Handle1:CAS:528:DyaK2sXjsFyjt7c%3D Occurrence Handle9223626

    Article  CAS  PubMed  Google Scholar 

  24. J Petrik T Zanic-Grubisic K Barisic S Pepeljnjak B Radic Z Ferencic I Cepelak (2003) ArticleTitleApoptosis and oxidative stress induced by ochratoxin A in rat kidney Arch Toxicol 77 685–693 10.1007/s00204-003-0501-8 Occurrence Handle10.1007/s00204-003-0501-8 Occurrence Handle1:CAS:528:DC%2BD3sXptleks7Y%3D Occurrence Handle13680094

    Article  CAS  PubMed  Google Scholar 

  25. E Rached E Pfeiffer W Dekant A Mally (2006) ArticleTitleOchratoxin A: Apoptosis and aberrant exit from mitosis due to perturbation of microtubule dynamics? Toxicol Sci 92 IssueID1 78–86 10.1093/toxsci/kfj213 Occurrence Handle10.1093/toxsci/kfj213 Occurrence Handle1:CAS:528:DC%2BD28XmsVegsL0%3D Occurrence Handle16641321

    Article  CAS  PubMed  Google Scholar 

  26. C Hanika WW Carlton EJ Hinsman J Tuite (1986) ArticleTitleCitrinin mycotoxicosis in the rabbit: Ultrastructural alterations Vet Pathol 23 IssueID3 245–253 Occurrence Handle1:CAS:528:DyaL28XktVWqu74%3D Occurrence Handle3727311

    CAS  PubMed  Google Scholar 

  27. DN Kitchen WW Carlton EJ Hinsman (1977) ArticleTitleOchratoxin A and citrinin induced nephrosis in Beagle dogs III. Terminal renal ultrastructural alterations Vet Pathol 14 IssueID4 392–406 Occurrence Handle1:STN:280:DyaE2s3jsleltg%3D%3D Occurrence Handle560743

    CAS  PubMed  Google Scholar 

  28. TP Brown RO Manning OJ Fletcher RD Wyatt (1986) ArticleTitleThe individual and combined effects of citrinin and ochratoxin A on renal ultrastructure in layer chicks Avian Dis 30 IssueID1 191–198 10.2307/1590632 Occurrence Handle10.2307/1590632 Occurrence Handle1:CAS:528:DyaL28Xkt1SitLk%3D Occurrence Handle3729863

    Article  CAS  PubMed  Google Scholar 

  29. K Hashimoto Y Morita (1957) ArticleTitleInhibitory effect of citrinin (C13H14O5) on the dehydrogenase system of rat’s kidney, liver and brain tissue, specially concerning the mechanism of polyurea observed in the poisoned animal Jpn J Pharmacol 7 48–54 Occurrence Handle1:CAS:528:DyaG1cXktFyhtA%3D%3D Occurrence Handle13513238

    CAS  PubMed  Google Scholar 

  30. FY Yu YC Liao CH Chang BH Liu (2006) ArticleTitleCitrinin induces apoptosis in HL-60 cells via activation of the mitochondrial pathway Toxicol Lett 161 IssueID2 143–151 10.1016/j.toxlet.2005.08.009 Occurrence Handle10.1016/j.toxlet.2005.08.009 Occurrence Handle1:CAS:528:DC%2BD2MXhtlWqtLvI Occurrence Handle16183218

    Article  CAS  PubMed  Google Scholar 

  31. A Knecht G Schwerdt M Gekle HU Humpf (2005) ArticleTitleCombinatory effects of citrinin and ochratoxin A in immortalized human proximal tubule cells Mycot Res 21 IssueID3 176–181 10.1007/BF02959258 Occurrence Handle10.1007/BF02959258 Occurrence Handle1:CAS:528:DC%2BD28XmslSrs7s%3D

    Article  CAS  Google Scholar 

  32. S Suzuki Y Kozuka T Satoh M Yamazaki (1975) ArticleTitleStudies on the nephrotoxicity of ochratoxin A in rats Toxicol Appl Pharmacol 34 479–490 10.1016/0041-008X(75)90141-6 Occurrence Handle10.1016/0041-008X(75)90141-6 Occurrence Handle1:CAS:528:DyaE28XosFaqtg%3D%3D Occurrence Handle1209641

    Article  CAS  PubMed  Google Scholar 

  33. AH Heussner DR Dietrich E O’Brien (2006) ArticleTitleIn vitro investigation of individual and combined cytotoxic effects of ochratoxin A and other selected mycotoxins on renal cells Toxicol In Vitro 20 IssueID3 332–341 10.1016/j.tiv.2005.08.003 Occurrence Handle10.1016/j.tiv.2005.08.003 Occurrence Handle1:CAS:528:DC%2BD28Xit1Cns7o%3D Occurrence Handle16140496

    Article  CAS  PubMed  Google Scholar 

  34. WO Berndt (1983) ArticleTitleTransport of citrinin by rat renal cortex Arch Toxicol 54 35–40 10.1007/BF00277813 Occurrence Handle10.1007/BF00277813 Occurrence Handle1:CAS:528:DyaL3sXlslWjsb8%3D Occurrence Handle6639352

    Article  CAS  PubMed  Google Scholar 

  35. C Robert N Curtis O Oscar Leonard (1994) ArticleTitleInteraction of citrinin and ochratoxin A Nat Toxins 2 IssueID3 124–131 10.1002/nt.2620020307 Occurrence Handle10.1002/nt.2620020307

    Article  Google Scholar 

  36. GJA Speijers MHM Speijers (2004) ArticleTitleCombined toxic effects of mycotoxins Toxicol Lett 153 IssueID1 91–98 10.1016/j.toxlet.2004.04.046 Occurrence Handle10.1016/j.toxlet.2004.04.046 Occurrence Handle1:CAS:528:DC%2BD2cXntlGltL4%3D Occurrence Handle15342085

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Prabhaker Dwivedi.

Additional information

Part of M.V.Sc thesis research work of first author, Deemed University, Indian Veterinary Research Institute, Izatnagar-243 122 (U. P.), India.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kumar, M., Dwivedi, P., Sharma, A.K. et al. Ochratoxin A and citrinin nephrotoxicity in New Zealand White rabbits: an ultrastructural assessment. Mycopathologia 163, 21–30 (2007). https://doi.org/10.1007/s11046-006-0079-9

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11046-006-0079-9

Keywords

Navigation