Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1981 Aug;68(2):556–559. doi: 10.1172/JCI110288

Dietary enrichment with the polyunsaturated fatty acid eicosapentaenoic acid prevents proteinuria and prolongs survival in NZB x NZW F1 mice.

J D Prickett, D R Robinson, A D Steinberg
PMCID: PMC370831  PMID: 7263863

Abstract

Prostaglandins and related compounds are active mediators of inflammation, but data concerning their role in the pathogenesis of the glomerulonephritis of New Zealand Black x New Zealand White (NZB x NZW) F1 mice are conflicting. Dietary eicosapentaenoic acid (EPA, C20:5), a fatty acid analogue of arachidonic acid (C20:4), has been shown to impair platelet aggregation in humans, apparently through inhibition of the synthesis of prostaglandins and thromboxanes from arachidonic acid. We report here the effects of a diet high in EPA on the development of renal disease and survival in female NZB x NZW F1 mice. Animals from 4--5 wk of age were fed diets containing 25% lipid, supplied either as beef tallow or menhaden oil, with fatty acid analysis of less than 0.05 and 14.4% EPA, respectively. In the first experiment, by 13.5 mo of age, mice on the beef tallow diet had all (9/9) developed proteinuria and the majority (6/9) had died, with renal histologic examination revealing severe glomerulonephritis. In contrast, none of 10 menhaden oil-fed animals had developed proteinuria, and all were alive at this time (P less than 0.005 for both proteinuria and survival). In a second experiment using 50 mice in each dietary group, 56% of the beef tallow group vs. none of the menhaden oil group had developed proteinuria at 9 mo of age (P less than 0.005). Native DNA binding at 6 mo of age was 23.9 +/- 14.7 vs. 10.1 +/- 9.7% in the beef and menhaden oil groups, respectively (P less than 0.01). Weights were similar in all groups, and there was no evidence of essential fatty acid deficiency in any group. These results demonstrate that a diet high in EPA protects NZB x NZW F1 mice from the development of glomerulonephritis.

Full text

PDF
556

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bang H. O., Dyerberg J., Hjøorne N. The composition of food consumed by Greenland Eskimos. Acta Med Scand. 1976;200(1-2):69–73. doi: 10.1111/j.0954-6820.1976.tb08198.x. [DOI] [PubMed] [Google Scholar]
  2. Bonta I. L., Bult H., Vincent J. E., Zijlstra F. J. Acute anti-inflammatory effects of aspirin and dexamethasone in rats deprived of endogenous prostaglandin precursors. J Pharm Pharmacol. 1977 Jan;29(1):1–7. doi: 10.1111/j.2042-7158.1977.tb11227.x. [DOI] [PubMed] [Google Scholar]
  3. Denko C. W. Modification of adjuvant inflammation in rats deficient in essential fatty acids. Agents Actions. 1976 Sep;6(5):636–641. doi: 10.1007/BF01971583. [DOI] [PubMed] [Google Scholar]
  4. Dyerberg J., Bang H. O., Stoffersen E., Moncada S., Vane J. R. Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet. 1978 Jul 15;2(8081):117–119. doi: 10.1016/s0140-6736(78)91505-2. [DOI] [PubMed] [Google Scholar]
  5. Fernandes G., Yunis E. J., Good R. A. Influence of diet on survival of mice. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1279–1283. doi: 10.1073/pnas.73.4.1279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Friend P. S., Fernandes G., Good R. A., Michael A. F., Yunis E. J. Dietary restrictions early and late: effects on the nephropathy of the NZB X NZW mouse. Lab Invest. 1978 Jun;38(6):629–632. [PubMed] [Google Scholar]
  7. Goetzl E. J. Mediators of immediate hypersensitivity derived from arachidonic acid. N Engl J Med. 1980 Oct 2;303(14):822–825. doi: 10.1056/NEJM198010023031421. [DOI] [PubMed] [Google Scholar]
  8. HOLMAN R. T. The ratio of trienoic: tetraenoic acids in tissue lipids as a measure of essential fatty acid requirement. J Nutr. 1960 Mar;70:405–410. doi: 10.1093/jn/70.3.405. [DOI] [PubMed] [Google Scholar]
  9. Hurd E. R., Johnston J. M., Okita J. R., MacDonald P. C., Ziff M., Gilliam J. W. Prevention of glomerulonephritis and prolonged survival in New Zealand Black/New Zealand White F1 hybrid mice fed an essential fatty acid-deficient diet. J Clin Invest. 1981 Feb;67(2):476–485. doi: 10.1172/JCI110056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huston D. P., Steinberg A. D. Animal models of human systemic lupus erythematosus. Yale J Biol Med. 1979 May-Jun;52(3):289–305. [PMC free article] [PubMed] [Google Scholar]
  11. Lambert P. H., Dixon F. J. Pathogenesis of the glomerulonephritis of NZB/W mice. J Exp Med. 1968 Mar 1;127(3):507–522. doi: 10.1084/jem.127.3.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lindsley H. B., Kysela S., Steinberg A. D. Nucleic acid antibodies in African trypanosomiasis: studies in Rhesus monkeys and man. J Immunol. 1974 Dec;113(6):1921–1927. [PubMed] [Google Scholar]
  13. Steinberg A. D., Gelfand M. C., Hardin J. A., Lowenthal D. T. Therapeutic studies in NZB/W mice. III. Relationship between renal status and efficacy of immunosuppressive drug therapy. Arthritis Rheum. 1975 Jan-Feb;18(1):9–14. doi: 10.1002/art.1780180102. [DOI] [PubMed] [Google Scholar]
  14. Vane J. R. Prostaglandins as mediators of inflammation. Adv Prostaglandin Thromboxane Res. 1976;2:791–801. [PubMed] [Google Scholar]
  15. Wedmore C. V., Williams T. J. Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature. 1981 Feb 19;289(5799):646–650. doi: 10.1038/289646a0. [DOI] [PubMed] [Google Scholar]
  16. Whitaker M. O., Wyche A., Fitzpatrick F., Sprecher H., Needleman P. Triene prostaglandins: prostaglandin D3 and icosapentaenoic acid as potential antithrombotic substances. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5919–5923. doi: 10.1073/pnas.76.11.5919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Zurier R. B., Damjanov I., Sayadoff D. M., Rothfield N. F. Prostaglandin E1 treatment of NZB/NZW F1 hybrid mice. II. Prevention of glomerulonephritis. Arthritis Rheum. 1977 Nov-Dec;20(8):1449–1456. doi: 10.1002/art.1780200802. [DOI] [PubMed] [Google Scholar]
  18. Zurier R. B., Sayadoff D. M., Torrey A. B., Rothfield N. F. Prostaglandin E treatment of NZB/NZW mice. Arthritis Rheum. 1977 Mar;20(2):723–728. doi: 10.1002/art.1780200213. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES