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Endotoxin provocation of experimental renal cystic disease - ScienceDirect


Kidney International

Volume 32, Issue 3, September 1987, Pages 329-334

Laboratory Investigation
Endotoxin provocation of experimental renal cystic disease

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Endotoxin provocation of experimental renal cystic disease. Germ free rats provide a unique model in which to assess biological response to environment. In 48 germ-free male, Sprague-Dawley rats we examined the consequences of oral exposure to nordihydroguaiaretic acid (NDGA), a nephrotoxin; to Staphylococcus epidermidis and bacillus species, non-endotoxin-containing bacteria; to Escherichia coli and Proteus mirabilis, endotoxin-containing bacteria; and injected E. coli endotoxin on peripheral leukocyte counts and renal morphology. Morphological changes were evaluated by light microscopy and scored blindly on a 0 to 4+ scale for 15 parameters of renal structure. Means of these renal "pathology scores" correlated with counts of polymorphonuclear leukocytes and lymphocytes in the peripheral blood. The highest counts and scores were found in rats given NDGA and exposed to endotoxin, either by injection or by oral feeding of endotoxin-containing bacteria. Counts and scores were lower in the absence of endotoxin and with non-endotoxin-containing bacteria, given alone or in combination with either NDGA or endotoxin. Results exclude bacterial colonization and intrarenal accumulation of NDGA as causes of nephropathy. They indicate that endotoxin and NDGA act synergistically to provoke renal damage in the germ free NDGA-fed rat and suggest that leukocytes are involved in the process.

References

  1. 1.
    J.S. Resnick, D.M. Brown, R.L. Vernier
    Normal development and experimental models of cystic renal disease
    K.D. Gardner (Ed.), in Cystic Diseases of the Kidney, J Wiley & Sons, New York (1976), pp. 221-241
  2. 2.
    T. Goodman, H.C. Grice, G.C. Becking, F.A. Salem
    A cystic nephropathy induced by nordihydroguaiaretic acid in the rat
    Lab Invest, 23 (1970), pp. 93-107
  3. 3.
    D.C. Dobyan, D. Hill, T. Lewis, R.E. Bulger
    Cyst formation in rat kidney induced by cis-Platinum administration
    Lab Invest, 45 (1981), pp. 260-268
  4. 4.
    S. Christensen, P. Ottosen, S. Olsen
    Severe functional and structural changes caused by lithium in the developing rat kidney
    Acta Path Microbiol Immunol Scand, 90 (1982), pp. 257-267
  5. 5.
    E. Boyland, C.E. Dukes, P.L. Grover, B.C.V. Mitchley
    The induction of renal tumours by feeding lead acetate to rats
    Br J Cancer, 16 (1962), pp. 283-288
  6. 6.
    K.D. Gardner, A.P. Evan
    Renal cystic disease induced by diphenylthiazole
    Kidney Int, 24 (1983), pp. 43-52
  7. 7.
    K.D. Gardner, A.P. Evan, W.P. Reed
    Accelerated renal cyst development in deconditioned germfree rats
    Kidney Int, 29 (1986), pp. 1116-1123
  8. 8.
    A.P. Evan, K.D. Gardner
    Nephron obstruction in nordihydroguaiaretic acid-induced renal cystic disease
    Kidney Int, 15 (1979), pp. 7-19
  9. 9.
    J.M. Zedalis, A.A. Leon, K.D. Gardner, M.D. Hylarides
    High performance liquid chromatographic determination of nordihydroguaiaretic acid
    Anal Letters, 19 (1986), pp. 1443-1456
  10. 10.
    S. Madigan, V. Lawrence
    Stats Plus: A General Statistics Package for the Apple II, Human Systems Dynamics, Northridge, CA (1982)
  11. 11.
    J.H. Zar
    Biostatistical Analysis, Prentice-Hall, Englewood Cliffs NJ (1974)
  12. 12.
    M. Pollard
    The germfree rat
    Pathobiol Ann, 1 (1971), pp. 83-94
  13. 13.
    H.A. Gordon, L. Pesti
    The gnotobiotic animal as a tool in the study of host microbial relationships
    Bacteriol Rev, 35 (1971), pp. 390-429
  14. 14.
    W.K. Bolton, F.R. Benton, J.G. Maclay, B.C. Sturgill
    Spontaneous glomerular sclerosis in aging Sprague-Dawley rats. I. Lesions associated with mesangial IgM deposits
    Am J Pathol, 85 (1976), pp. 277-302
  15. 15.
    B.S. Reddy, J.R. Pleasants, B.S. Wostmann
    Metabolic enzymes in liver and kidney of the germfree rat
    Biochim Biophys Acta, 320 (1973), pp. 1-8
  16. 16.
    J.L. Valentine, L. McKenzie, F. Kovarik
    Gas chromatographic determination of nordihydroguaiaretic acid in Larrea divaricata
    Anal Letters, 17 (1984), pp. 1617-1626
  17. 17.
    P.C. Duisberg, L.B. Shires, C.W. Botkin
    Determination of nordihydroguaiaretic acid in the leaf of Larrea divaricata (Creosote bush)
    Anal Chem, 21 (1949), pp. 1393-1396
  18. 18.
    O. Gisvold, E. Thaker
    Lignans from Larrea divaricata
    J Pharm Sci, 63 (1974), pp. 1905-1907
  19. 19.
    J. Harvey, D.J. Osborne
    A rapid method for detecting inhibitors of both cyclo-oxygenase and lipoxygenase metabolites of arachidonic acid
    J Pharmacol Meth, 9 (1983), pp. 147-155
  20. 20.
    H.C. Grice, G. Becking, T. Goodman
    Toxic properties of nordihydroguaiaretic acid
    Fd Cosmet Toxicol, 6 (1968), pp. 155-161
  21. 21.
    C.R. Smart, R.K. Hogle, R.K. Robins, A.D. Broom, D. Bartholomew
    An interesting observation on nordihydroguaiaretic acid (NSC-4291; NDGA) and a patient with malignant melanoma—a preliminary report
    Cancer Chemother Rep, 53 (1969), pp. 147-151
  22. 22.
    D.C. Morrison, R.L. Duncan, S.A. Goodman
    In vivo biological activities of endotoxin
    J.W. ten Cate, H.R. Buller, A. Sturk, J. Levin (Eds.), Bacterial Endotoxins: Structure, Biomedical Significance, and Detection with the Limulus Amebocyte Lysate Test, Alan R. Liss, Inc., New York (1984), pp. 81-98
  23. 23.
    J.A. Savige, S.H. Saverymuttu, A.J. Pinching
    A functional comparison of III indium-labelled elicited peripheral blood neutrophils and peritoneal neutrophils in the rat
    Clin Exp Immunol, 58 (1984), pp. 737-744
  24. 24.
    W.F. Keane, G. Gekker, P.M. Schlievert, P.K. Peterson
    Enhancement of endotoxin-induced isolated renal tubular cell injury by toxic shock syndrome toxin 1
    Am J Pathol, 122 (1986), pp. 169-176
  25. 25.
    J.D. Conger, S.A. Falk, S.J. Guggenheim
    Glomerular dynamics and morphologic changes in the generalized Shwartzman reaction in postpartum rats
    J Clin Invest, 67 (1981), pp. 1334-1346
  26. 26.
    T. Ando
    An ultrastructural and cytochemical study of the rat kidney in experimentally induced endotoxin shock
    Nippon Geka Gakkai Zasshi, 85 (1984), pp. 835-848
  27. 27.
    B. Osterud
    Interaction of endotoxins, blood elements and the vessel wall
    J.W. ten Cate, H.R. Buller, A. Sturk, J. Levin (Eds.), Bacterial Endotoxins: Structure, Biomedical Significance, and Detection with the Limulus Amebocyte Test, Alan R. Liss, Inc., New York (1984), pp. 67-78
  28. 28.
    T. Okegawa, K. Deschryver-Kecskemeti, P. Needleman
    Endotoxin induces chronic prostaglandin and thromboxane synthesis from ureter-obstructed kidneys: Role of inflammatory cells
    J Pharmacol Exper Ther, 225 (1983), pp. 213-218
  29. 29.
    A.P. Evan, K.D. Gardner, J. Bernstein
    Polypoid and papillary epithelial hyperplasia: A potential cause of ductal obstruction in adult polycystic disease
    Kidney Int, 16 (1979), pp. 743-750
  30. 30.
    H. Selye, B. Tuchweber, L. Bertok
    Effect of lead acetate on the susceptibility of rats to bacterial endotoxins
    J Bacteriol, 91 (1966), pp. 884-890
  31. 31.
    J.P. Nolan, R.C. Venuto, G.S. Goldman
    Role of endotoxin in glycerol-induced renal failure in the rat
    Clin Sci Mol Med, 54 (1978), pp. 615-620
  32. 32.
    B.M. Tune, C.Y. Hsu
    Augmentation of antibiotic nephrotoxicity by endotoxemia in the rabbit
    J Pharmacol Exp Ther, 234 (1985), pp. 425-430
  33. 33.
    V.C. Ross, C.W. Twohy
    Endotoxins and medical devices
    J.W. ten Cate, H.R. Buller, A. Sturk, J. Levin (Eds.), Bacterial Endotoxins: Structure, Biomedical Significance, and Detection with the Limulus Amebocyte Lysate Test, Alan R. Liss, Inc, New York (1985), pp. 267-280
  34. 34.
    M.E. Wilson
    Effects of bacterial endotoxins on neutrophil function
    Rev Infect Dis, 7 (1985), pp. 404-418
  35. 35.
    T.W. Williams, J.M. Lyons, A.I. Braude
    In vitro lysis of target cells by rat polymorphonuclear leukocytes isolated from acute pyelonephritis exudates
    J Immunol, 119 (1977), pp. 671-674
  36. 36.
    C.J. Kelly, M.D. Clayman, E.G. Neilson
    Immunoregulation in experimental interstitial nephritis
    J Immunol, 136 (1986), pp. 903-907
  37. 37.
    G. Weissmann, J.E. Smolen, H.M. Korchak
    Release of inflammatory mediators from stimulated neutrophils
    N Engl J Med, 303 (1980), pp. 27-34
  38. 38.
    B.M. Babior
    Oxygen-dependent microbial killing by phagocytes
    N Engl J Med, 298 (1978), pp. 659-668
    721-725
  39. 39.
    B. Kalyanaraman, P.G. Sohnle
    Generation of free radical intermediates from foreign compounds by neutrophil-derived oxidants
    J Clin Invest, 75 (1985), pp. 1618-1622
  40. 40.
    S.J. Klebanoff
    Oxygen metabolism and the toxic properties of phagocytes
    Ann Int Med, 93 (1980), pp. 480-489
  41. 41.
    A.L. Tappel, A.G. Marr
    Effect of alpha-tocopherol, propyl gallate, and nordihydroguaiaretic acid on enzymatic reactions
    J Agric Food Chem, 2 (1954), pp. 554-558
  42. 42.
    N.R. Bachur, S.L. Gordon, M.V. Gee, H. Kon
    NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals
    Med Sci, 76 (1979), pp. 951-957
  43. 43.
    K.D. Gardner, A.P. Evan
    Cystic kidneys: An enigma evolves
    Am J Kid Dis, 3 (1984), pp. 403-413
  44. 44.
    M.S. Rhee, D. McGoldrick, H.J. Meuwissen
    Serum factor from patients with chronic renal failure enhances polymorphonuclear leukocyte oxidative metabolism
    Nephron, 42 (1986), pp. 6-13
  45. 45.
    P.A. Gabow, D.W. Ikle, J.H. Holmes
    Polycystic kidney disease: Prospective analysis of nonazotemic patients and family members
    Ann Intern Med, 101 (1984), pp. 238-247

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Copyright © 1987 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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