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. 1979 Jul;25(1):337–344. doi: 10.1128/iai.25.1.337-344.1979

Endotoxin toxicity in rats with 6-sulfanilamidoindazole arthritis.

M L Miller, C O Samuelson, J R Ward, R N Hiramoto
PMCID: PMC414457  PMID: 383619

Abstract

Seven oral administrations of 6-sulfanilamidoindazole (6-SAI) to 10- to 12-month-old rats sensitized the animals to endotoxin, with dosages as small as 2.5 microgram causing death in 80% of animals. Endotoxin in a dosage of 3,000 microgram was not lethal for nonmedicated control animals. 6-SAI-treated 1-month-old rats were not as sensitive to endotoxin as aged animals. The sulfonamide-induced sensitivity to endotoxin could not be passively transferred and could not be explained by blockade of the reticuloendothelial system or impairment of endotoxin detoxification. 6-SAI administration was associated with both depletion of liver glycogen and lowering of blood glucose concentration without changes in blood lactic acid concentration. Disseminated intravascular coagulation is believed to be involved in the pathogenesis of shock and death as evidenced by: (i) concomitant decreases in plasma fibrinogen concentration and elevations in fibrin degradation products after endotoxin challenge; (ii) protection against lethal actions of endotoxin by pretreatment with heparin. Treatment of 6-SAI-medicated rats with glucocorticoids before endotoxin challenge protected the animals against lethal doses of endotoxin and prevented deposition of fibrin thrombi in the glomerular capillaries.

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Selected References

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

  1. ABERNATHY R. S., SPINK W. W. Resistance to endotoxin after protection against initial lethal challenge with adrenocorticosteroids or chlorpromazine. Proc Soc Exp Biol Med. 1957 Jul;95(3):580–581. doi: 10.3181/00379727-95-23297. [DOI] [PubMed] [Google Scholar]
  2. BENACERRAF B., THORBECKE G. J., JACOBY D. Effect of zymosan on endotoxin toxicity in mice. Proc Soc Exp Biol Med. 1959 Apr;100(4):796–799. doi: 10.3181/00379727-100-24781. [DOI] [PubMed] [Google Scholar]
  3. BIOZZI G., BENACERRAF B., HALPERN B. N. Quantitative study of the granulopectic activity of the reticulo-endothelial system. II. A study of the kinetics of the R. E. S. in relation to the dose of carbon injected; relationship between the weight of the organs and their activity. Br J Exp Pathol. 1953 Aug;34(4):441–457. [PMC free article] [PubMed] [Google Scholar]
  4. BRAUDE A. I., CAREY F. J., ZALESKY M. Studies with radioactive endotoxin. II. Correlation of physiologic effects with distribution of radioactivity in rabbits injected with radioactive sodium chromate. J Clin Invest. 1955 Jun;34(6):858–866. doi: 10.1172/JCI103141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bradley S. G., Adams A. C., Smith M. C. Potentiation of the toxicity of mithramycin by bacterial lipopolysaccharide. Antimicrob Agents Chemother. 1975 Mar;7(3):322–327. doi: 10.1128/aac.7.3.322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bradley S. G., Bond J. S. Toxicity, clearance, and metabolic effects of pactamycin in combination with bacterial lipopolysaccharide. Toxicol Appl Pharmacol. 1975 Feb;31(2):208–221. doi: 10.1016/0041-008x(75)90157-x. [DOI] [PubMed] [Google Scholar]
  7. Cook J. A., Marconi E. A., Di Luzio N. R. Lead, cadmium, endotoxin interaction: effect on mortality and hepatic function. Toxicol Appl Pharmacol. 1974 May;28(2):292–302. doi: 10.1016/0041-008x(74)90016-7. [DOI] [PubMed] [Google Scholar]
  8. Corrigan J. J., Jr, Jordan C. M. Heparin therapy in septicemia with disseminated intravascular coagulation. N Engl J Med. 1970 Oct 8;283(15):778–782. doi: 10.1056/NEJM197010082831502. [DOI] [PubMed] [Google Scholar]
  9. Crafton C. G., Di LUZIO N. R. Relationship of reticuloendothelial functional activity to endotoxin lethality. Am J Physiol. 1969 Sep;217(3):736–742. doi: 10.1152/ajplegacy.1969.217.3.736. [DOI] [PubMed] [Google Scholar]
  10. DRUCKER W. R., DEKIEWIET J. C. GLUCOSE UPTAKE BY DIAPHRAGMS FROM RATS SUBJECTED TO HEMORRHAGIC SHOCK. Am J Physiol. 1964 Feb;206:317–320. doi: 10.1152/ajplegacy.1964.206.2.317. [DOI] [PubMed] [Google Scholar]
  11. Dobson E. L., Kelly L. S. The combined stimulation of the reticuloendothelial system by estradiol and endotoxin. J Reticuloendothel Soc. 1973 Jan;13(1):61–69. [PubMed] [Google Scholar]
  12. ENGEL F. L. The significance of the metabolic changes during shock. Ann N Y Acad Sci. 1952 Sep;55(3):381–393. doi: 10.1111/j.1749-6632.1952.tb26554.x. [DOI] [PubMed] [Google Scholar]
  13. FARRAR W. E., Jr, WATSON J. G. HYPOGLYCEMIA FOLLOWING ENDOTOXIN ADMINISTRATION IN ANIMALS WITH LIVER DAMAGE. Proc Soc Exp Biol Med. 1964 Mar;115:833–837. doi: 10.3181/00379727-115-29051. [DOI] [PubMed] [Google Scholar]
  14. FINKELSTEIN R. A. OBSERVATIONS ON MODE OF ACTION OF ENDOTOXIN IN CHICK EMBRYOS. Proc Soc Exp Biol Med. 1964 Mar;115:702–707. doi: 10.3181/00379727-115-29012. [DOI] [PubMed] [Google Scholar]
  15. Filkins J. P. Bioassay of endotoxin inactivation in the lead-sensitized rat. Proc Soc Exp Biol Med. 1970 Jul;134(3):610–612. doi: 10.3181/00379727-134-34844. [DOI] [PubMed] [Google Scholar]
  16. Filkins J. P., Cornell R. P. Depression of hepatic gluconeogenesis and the hypoglycemia of endotoxin shock. Am J Physiol. 1974 Oct;227(4):778–781. doi: 10.1152/ajplegacy.1974.227.4.778. [DOI] [PubMed] [Google Scholar]
  17. Filkins J. P., Di Luzio N. R. Heparin protection in endotoxin shock. Am J Physiol. 1968 May;214(5):1074–1077. doi: 10.1152/ajplegacy.1968.214.5.1074. [DOI] [PubMed] [Google Scholar]
  18. GOOD R. A., THOMAS L. Studies on the generalized Shwartzman reaction. II. The production of bilateral cortical necrosis of the kidneys by a single injection of bacterial toxin in rabbits previously treated with thorotrast or trypan blue. J Exp Med. 1952 Dec;96(6):625–641. doi: 10.1084/jem.96.6.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. GOOD R. A., THOMAS L. Studies on the generalized Shwartzman reaction. IV. Prevention of the local and generalized Shwartzman reactions with heparin. J Exp Med. 1953 Jun;97(6):871–888. doi: 10.1084/jem.97.6.871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. GOODWIN J. F. Estimation of plasma fibrinogen, using sodium sulfite fractionation. Am J Clin Pathol. 1961 Mar;35:227–232. doi: 10.1093/ajcp/35.3.227. [DOI] [PubMed] [Google Scholar]
  21. Govier W. C. Reticuloendothelial cells as the site of sulfanilamide acetylation in the rabbit. J Pharmacol Exp Ther. 1965 Nov;150(2):305–308. [PubMed] [Google Scholar]
  22. HARDAWAY R. M., HUSNI E. A., GEEVER E. F., NOYESHE, BURNS J. W. Endotoxin shock. A manifestation of intravascular coagulation. Ann Surg. 1961 Nov;154:791–802. doi: 10.1097/00000658-196111000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. KEMP A., VAN HEIJNINGEN A. J. M. K. A colorimetric micro-method for the determination of glycogen in tissues. Biochem J. 1954 Apr;56(4):646–648. doi: 10.1042/bj0560646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Latour J. G., Leger C. Prevention by glucocorticoids of disseminated intravascular coagulation induced by endotoxin: mechanisms. J Lab Clin Med. 1975 Jun;85(6):934–949. [PubMed] [Google Scholar]
  25. Latour J. G., McKay D. G., Nasu K. Prevention of the generalized Schwartzman reaction by glucocorticoids. Am J Obstet Gynecol. 1972 Aug 1;113(7):863–867. doi: 10.1016/0002-9378(72)90648-5. [DOI] [PubMed] [Google Scholar]
  26. Latour J. G., Prejean J. B., Margaretten W. Corticosteroids and the generalized Shwartzman reaction. Mechanisms of sensitization in the rabbit. Am J Pathol. 1971 Oct;65(1):189–202. [PMC free article] [PubMed] [Google Scholar]
  27. Leavelle D. E., Mertens B. F., Bowie E. J., Owen C. A., Jr Staphylococcal clumping on microtiter plates: a rapid, simple method for measuring fibrinogen split products. Am J Clin Pathol. 1971 Apr;55(4):452–457. doi: 10.1093/ajcp/55.4.452. [DOI] [PubMed] [Google Scholar]
  28. Levine S., Sowinski R. Cyclophosphamide--induced cerebral and visceral lesions in rats. Enhancement by endotoxins. Arch Pathol. 1974 Sep;98(3):177–182. [PubMed] [Google Scholar]
  29. Levine S., Sowinski R. Endotoxin toxicity in rats is enhanced by tilorone. Proc Soc Exp Biol Med. 1976 Feb;151(2):329–332. doi: 10.3181/00379727-151-39203. [DOI] [PubMed] [Google Scholar]
  30. Lipinski B., Wegrzynowicz Z., Budzynski A. Z., Kopeć M., Latallo Z. S., Kowalski E. Soluble unclottable complexes formed in the presence of fibrinogen degradation products (FDP) during the fibrinogen-fibrin conversion and their potential significance in pathology. Thromb Diath Haemorrh. 1967 Feb 28;17(1-2):65–77. [PubMed] [Google Scholar]
  31. MIELENS Z. E., ROZITIS J., Jr ACUTE PERI-ARTICULAR INFLAMMATION INDUCED IN RATS BY ORAL 6-SULFANILYLINDAZOLE. Proc Soc Exp Biol Med. 1964 Dec;117:751–754. doi: 10.3181/00379727-117-29687. [DOI] [PubMed] [Google Scholar]
  32. Marecki N. M., Bradley S. G. Enhanced toxicity for mice of combinations of bacterial endotoxin with antitumor drugs. Antimicrob Agents Chemother. 1973 May;3(5):599–606. doi: 10.1128/aac.3.5.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Margaretten W., McKay D. G., Phillips L. L. The effect of heparin on endotoxin shock in the rat. Am J Pathol. 1967 Jul;51(1):61–68. [PMC free article] [PubMed] [Google Scholar]
  34. McKAY D. G., SHAPIRO S. S. Alterations in the blood coagulation system induced by bacterial endotoxin. I. In vivo (generalized Shwartzman reaction). J Exp Med. 1958 Mar 1;107(3):353–367. doi: 10.1084/jem.107.3.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Miller M. L., Samuelson C. O., Ward J. R. Hematologic and serologic studies in 6-sulfanilamidoindazole arthritis. Arthritis Rheum. 1978 Jul-Aug;21(6):681–689. doi: 10.1002/art.1780210612. [DOI] [PubMed] [Google Scholar]
  36. Miller M. L., Ward J. R., Cole B. C., Swinyard E. A. 6-sulfanilamidoindazole induced arthritis and periarthritis in rats. A new model of experimental inflammation. Arthritis Rheum. 1970 May-Jun;13(3):222–235. doi: 10.1002/art.1780130303. [DOI] [PubMed] [Google Scholar]
  37. Mills L. C. Corticosteroids in endotoxic shock. Proc Soc Exp Biol Med. 1971 Nov;138(2):507–511. doi: 10.3181/00379727-138-35928. [DOI] [PubMed] [Google Scholar]
  38. PIETTE M., PIETTE C. Numération des plaquettes sanguines utilisant un liquide hypotonique à base de chlorhydrate de procaine. Sang. 1959;30(2):144–151. [PubMed] [Google Scholar]
  39. Rose W. C., Bradley S. G. Enhanced toxicity for mice of combinations of antibiotics with Escherichia coli cells or Salmonella typhosa endotoxin. Infect Immun. 1971 Nov;4(5):550–555. doi: 10.1128/iai.4.5.550-555.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rose W. C., Bradley S. G., Lee I. P. Potentiation of the toxicity of several antitumor agents by Salmonella typhosa endotoxin. Toxicol Appl Pharmacol. 1972 Sep;23(1):102–111. doi: 10.1016/0041-008x(72)90209-8. [DOI] [PubMed] [Google Scholar]
  41. Rutenburg S., Skarnes R., Palmerio C., Fine J. Detoxification of endotoxin by perfusion of liver and spleen. Proc Soc Exp Biol Med. 1967 Jun;125(2):455–459. doi: 10.3181/00379727-125-32118. [DOI] [PubMed] [Google Scholar]
  42. SKARNES R. C., ROSEN F. S., SHEAR M. J., LANDY M. Inactivation of endotoxin by a humoral component. II. Interaction of endotoxin with serum and plasma. J Exp Med. 1958 Nov 1;108(5):685–699. doi: 10.1084/jem.108.5.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. SMITH R. T., BRAUDE A. I., CAREY F. J. The distribution of Cr51 labeled E. coli endotoxin in the generalized Shwartzman reaction. J Clin Invest. 1957 May;36(5):695–699. doi: 10.1172/JCI103471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Selye H., Tuchweber B., Bertók L. Effect of lead acetate on the susceptibility of rats to bacterial endotoxins. J Bacteriol. 1966 Feb;91(2):884–890. doi: 10.1128/jb.91.2.884-890.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Seyberth H. W., Schmidt-Gayk H., Hackenthal E. Toxicity, clearance and distribution of endotoxin in mice as influenced by actinomycin D, cycloheximide, -amanitin and lead acetate. Toxicon. 1972 Aug;10(5):491–500. doi: 10.1016/0041-0101(72)90175-4. [DOI] [PubMed] [Google Scholar]
  46. Shands J. W., Jr, Miller V., Martin H. The hypoglycemic activity of endotoxin. I. Occurrence in animals hyperreactive to endotoxin. Proc Soc Exp Biol Med. 1969 Feb;130(2):413–417. doi: 10.3181/00379727-130-33568. [DOI] [PubMed] [Google Scholar]
  47. Sigg E. B., Graeme M. L., John M. Induction of periarthritis by oral administration of 6-sulfanilamidoindazole and its treatment in rats. J Pharmacol Exp Ther. 1967 Jul;157(1):214–219. [PubMed] [Google Scholar]
  48. Skarnes R. C. Host defense against bacterial endotoxemia: mechanism in normal animals. J Exp Med. 1970 Aug 1;132(2):300–316. doi: 10.1084/jem.132.2.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Swingle K. F., Chang S. F., Erickson E. H. Impaired metabolic handling of drugs in rats with arthritis induced by 6-sulfonanilamidoindazole. Biochem Pharmacol. 1978;27(20):2395–2398. doi: 10.1016/0006-2952(78)90350-7. [DOI] [PubMed] [Google Scholar]
  50. THOMAS L., GOOD R. A. The effect of cortisone on the Shwartzman reaction; the production of lesions resembling the dermal and generalized Shwartzman reactions by a single injection of bacterial toxin in cortisone-treated rabbits. J Exp Med. 1952 Apr;95(4):409–428. doi: 10.1084/jem.95.4.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. THOMAS L., SMITH R. T., VON KORFF R. Cold-precipitation by heparin of a protein in rabbit and human plasma. Proc Soc Exp Biol Med. 1954 Aug-Sep;86(4):813–818. doi: 10.3181/00379727-86-21241. [DOI] [PubMed] [Google Scholar]
  52. TRAPANI R. J., WARAVDEKAR V. S., LANDY M., SHEAR M. J. In vitro inactivation of endotoxin by an intracellular agent from rabbit liver. J Infect Dis. 1962 Mar-Apr;110:135–142. doi: 10.1093/infdis/110.2.135. [DOI] [PubMed] [Google Scholar]
  53. Trejo R. A., Di Luzio N. R. Impaired detoxification as a mechanism of lead acetate-induced hypersensitivity to endotoxin. Proc Soc Exp Biol Med. 1971 Mar;136(3):889–893. doi: 10.3181/00379727-136-35388. [DOI] [PubMed] [Google Scholar]
  54. Trejo R. A., Loose L. D., Di Luzio N. R. Influence of diethylstilbestrol (DES) on reticuloendothelial function, tissue distribution, and detoxication of S. enteritidis endotoxin. J Reticuloendothel Soc. 1972 Jan;11(1):88–97. [PubMed] [Google Scholar]
  55. Ward J. R., Miller M. L., Burch F. Local and generalized Shwartzman reaction induced in rats with 6-sulfanilamidoindazole arthritis. Arthritis Rheum. 1973 Jul-Aug;16(4):491–498. doi: 10.1002/art.1780160409. [DOI] [PubMed] [Google Scholar]

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