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Molecular pathology of acute kidney injury in a choline-deficient model and fish oil protective effect

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Abstract

Purpose

The aim of this work was to investigate the potential protective effects of fish oil on the basis of kidney transcriptomic data on a nutritional experimental model.

Methods

Male weanling Wistar rats were divided into four groups and fed choline-deficient (CD) and choline-supplemented (CS) diets with vegetable oil (VO) and menhaden oil (MO): CSVO, CDVO, CSMO and CDMO. Animals were killed after receiving the diets for 6 days. Total RNA was purified from the right kidney and hybridized to Affymetrix GeneChip Rat Gene 1.0 ST Array. Differentially expressed genes were analyzed.

Results

All CSVO, CSMO and CDMO rats showed no renal alterations, while all CDVO rats showed renal cortical necrosis. A thorough analysis of the differential expression between groups CSMO and CDMO was carried out. There were no differential genes for p < 0.01. The analysis of the differential expression between groups CSVO and CSMO revealed 32 genes, 11 were over-expressed and 21 were under-expressed in CSMO rats.

Conclusions

This work was part of a large set of experiments and was used in a hypothesis-generating manner. The comprehensive analysis of genetic expression allowed confirming that menhaden oil has a protective effect on this nutritional experimental model and identifying 32 genes that could be responsible for that protection, including Gstp1. These results reveal that gene changes could play a role in renal injury.

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References

  1. Zeisel SH, Blusztajn JK (1994) Choline and human nutrition. Annu Rev Nutr 14:269–296

    Article  CAS  Google Scholar 

  2. Institute of Medicine of the National Academies (1998) Dietary reference intakes for thiamine, riboflavin, niacin, vitamin B6, foltae, vitamin B12, pantothenic acid, biotin, and choline. Choline. The National Academies Press, Washington DC, pp 390–422

  3. Zeisel SH, da Costa KA (2009) Choline: an essential nutrient for public health. Nutr Rev 67:615–623

    Article  Google Scholar 

  4. Montes de Oca M, Perazzo JC, Monserrat AJ, Arrizurieta de Muchnik EE (1980) Acute renal failure induced by choline deficiency: structural functional correlations. Nephron 26:41–48

    Article  CAS  Google Scholar 

  5. Monserrat AJ, Musso AM, Tartas N, Nicastro MA, Konopka HF, Arienti di García I, Sanchez Avalos JC (1981) Consumption coagulopathy in acute renal failure induced by hypolipotropic diets. Nephron 28:276–284

    Article  CAS  Google Scholar 

  6. Fewster ME, Hall MO (1967) The renal phospholipid composition of choline-deficient rats. Lipids 2:239–243

    Article  CAS  Google Scholar 

  7. Monserrat AJ, Porta EA, Ghoshal AK, Hartman SB (1974) Sequential renal lipid changes in weanling rats fed a choline-deficient diet. J Nutr 104:1496–1502

    CAS  Google Scholar 

  8. Simon JB, Scheig R, Klatskin G (1968) Relationship of early lipid changes in kidney and liver to the hemorrhagic renal necrosis of choline-deficient rats. Lab Invest 19:503–509

    CAS  Google Scholar 

  9. O’Neal RM, Still WJS, Hartroft WS (1961) Increased lipotropic requirements with renal necrosis induced in rats by high-fat diets. J Nutr 75:309–318

    Google Scholar 

  10. Monserrat AJ, Romero M, Lago N, Aristi C (1995) Protective effect of coconut oil on renal necrosis occurring in rats fed a methyl-deficient diet. Ren Fail 17:525–537

    Article  CAS  Google Scholar 

  11. Monserrat AJ, Cutrin JC, Coll C (2000) Protective effect of myristic acid on renal necrosis occurring in rats fed a methyl-deficient diet. Res Exp Med (Berl) 199:195–206

    CAS  Google Scholar 

  12. Courrèges C, Caruso C, Klein J, Monserrat AJ (2002) Protective effect of menhaden oil on renal necrosis occurring in weanling rats fed a methyl-deficient diet. Nutr Res 22:1077–1089

    Article  Google Scholar 

  13. Takayama J, Takaoka M, Supino Y, Yamamoto Y, Ohkita M, Matsumura Y (2007) Sex difference in ischemic acute renal failure in rats: approach by proteomic analysis. Biol Pharm Bull 30:1905–1912

    Article  CAS  Google Scholar 

  14. NIH Guide for the Care and Use of Laboratory Animals (2011) The National Academies Press, Washington

  15. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ et al (2003) Exploration, normalization and summaries of high density oligonucleotide array probe level data. Biostatistics 4:249–264

    Article  Google Scholar 

  16. Smyth GK, Speed T (2003) Normalization of cDNA microarray data. Methods 31:265–273

    Article  CAS  Google Scholar 

  17. Smyth GK (2004) Linear models and empirical Bayes methods for assessing differential expression in microarray experiments: Stat Appl Genet Mol Biol 3. doi:10.2202/1544-6115.1027

  18. Fresno C, Llera AS, Girotti MR, Valacco MP, López JA, Podhajcer OL, Balzarini MG, Prada F, Fernández EA (2012) The multi-reference contrast method: facilitating set enrichment analysis. Comput Biol Med 42:188–194

    Article  Google Scholar 

  19. Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57

    Article  CAS  Google Scholar 

  20. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene Ontology: tool for the unification of biology. Nat Genet 25:25–29

    Article  CAS  Google Scholar 

  21. Bellomo R (2006) The epidemiology of acute renal failure: 1975 versus 2005. Curr Opin Crit Care 12:557–560

    Article  Google Scholar 

  22. Ympa YP, Sakr Y, Reinhart K, Vincent JL (2005) Has mortality from acute renal failure decreased? A systematic review of the literature. Am J Med 118:827–832

    Article  Google Scholar 

  23. Webb S, Dobb G (2007) ARF, ATN or AKI? It’s now acute kidney injury. Anaesth Intensive Care 35:843–844

    CAS  Google Scholar 

  24. He JC, Chuang PY, Ma’ayan A, Iyengar R (2012) Systems biology of kidney diseases. Kidney Int 81:22–39

    Article  CAS  Google Scholar 

  25. Nettleton JA (1995) Omega-3 fatty acids, and health. Chapman & Hall, New York

    Book  Google Scholar 

  26. Verhoef P (2007) Homocysteine-an indicator of healthy diet? Am J Clin Nutr 85:1446–1447

    CAS  Google Scholar 

  27. Herbert V (1997) Vitamina B12. In Conceptosd actuales sobre nutrición, 7th edn. OMS, Washington, pp 203

  28. Scott JS, Treston AM, Bowman EP, Owens JA, Cooksley WG (1984) The regulatory roles of liver and kidney in cobalamin (vitamin B12) metabolism in the rat the uptake and intracellular binding of cobalamin and the activity of the cobalamin-dependent enzymes in response to varying cobalamin supply. Cli Sci (Lond) 67:299–306

    CAS  Google Scholar 

  29. Monserrat AJ, Ghoshal A, Hartroft W, Porta E (1969) Lipoperoxidation in the pathogenesis of renal necrosis in choline-deficient rats. Am J Pathol 55:163–190

    CAS  Google Scholar 

  30. Repetto MG, Ossani G, Monserrat A, Boveris A (2010) Oxidative damage: the biochemical mechanism of cellular injury and necrosis in choline deficiency. Exp Mol Pathol 88:143–149

    Article  CAS  Google Scholar 

  31. Newberne PM, Bresnahan MR, Kula N (1969) Effect of two synthetic antioxidants, vitamin E, and ascorbic acid on the choline-deficient rat. J Nutr 97:219–231

    CAS  Google Scholar 

  32. Ossani G, Dalghi M, Repetto M (2007) Oxidative damage and lipid peroxidation in the kidney of choline-deficient rats. Front Biosci 12:1174–1183

    Article  CAS  Google Scholar 

  33. Ossani G (2010) Deficiencia de colina y patogenia de la insuficiencia renal aguda. PhD Thesis. University of Buenos Aires. Department of Pathology

  34. Bagshaw SM (2006) The long-term outcome after acute renal failure. Curr Opin Crit Care 12:561–566

    Article  Google Scholar 

  35. Brenner BM, Rector FC (2007) The kidney. Saunders, Philadelphia

    Google Scholar 

  36. Siew ED, Ware LB, Ikizler TA (2011) Biological markers of acute kidney injury. J Am Soc Nephrol 5:810–820

    Article  Google Scholar 

Download references

Acknowledgments

We thank Mariana dos Santos and Silvia Caram for technical assistance, Myrthala Duguid (Head of the Library at CEMIC University Institute), and Valeria Melia for English editing of the manuscript. This paper was partially supported by a grant from CONICET and University of Buenos Aires, Argentina.

Conflict of interest

All the authors declare no conflicts of interest in this protocol.

Author information

Authors and Affiliations

  1. Departamento de Patología, Facultad de Medicina, Centro de Patología Experimental y Aplicada (CPEA), Universidad de Buenos Aires, J. E. Uriburu 950, 5º piso, (C1114AAD), Ciudad Autónoma de Buenos Aires, Argentina

    Valeria Denninghoff, Georgina Ossani, Ana Uceda & Alberto Monserrat

  2. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno” (CEMIC), Ciudad Autónoma de Buenos Aires, Argentina

    Valeria Denninghoff, Alejandra Avagnina & Boris Elsner

  3. Laboratorio de Genómica Comparativa del Desarrollo Vegetal, Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas (IIB-BA, CONICET), Buenos Aires, Argentina

    Matias Rugnone

  4. Facultad de Ingeniería, Universidad Católica de Córdoba, Córdoba, Argentina

    Elmer Fernández, Cristóbal Fresno & German González

  5. Medicina Nuclear, Laboratorio de Vitaminas, Hospital Británico, Ciudad Autónoma de Buenos Aires, Argentina

    Maria Luisa Díaz

Authors
  1. Valeria Denninghoff
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  2. Georgina Ossani
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  3. Ana Uceda
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  4. Matias Rugnone
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  5. Elmer Fernández
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  6. Cristóbal Fresno
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  7. German González
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  8. Maria Luisa Díaz
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  9. Alejandra Avagnina
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  10. Boris Elsner
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  11. Alberto Monserrat
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Corresponding author

Correspondence to Valeria Denninghoff.

Additional information

Valeria Denninghoff, Elmer Fernández and Alberto Monserrat: Member of the Research Career at the National Scientific and Technical Research Council (CONICET), Argentina.

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Denninghoff, V., Ossani, G., Uceda, A. et al. Molecular pathology of acute kidney injury in a choline-deficient model and fish oil protective effect. Eur J Nutr 53, 897–906 (2014). https://doi.org/10.1007/s00394-013-0593-8

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  • DOI: https://doi.org/10.1007/s00394-013-0593-8

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