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. 1993 Feb;142(2):519–528.

U75412E, a lazaroid, prevents progressive burn ischemia in a rat burn model.

M Choi 1, H P Ehrlich 1
PMCID: PMC1886741  PMID: 8434647

Abstract

Thermal energy causes an immediate, irreversible injury at the burn site, followed by a delayed, reversible tissue loss in the area surrounding the burn site due to progressive ischemia. We investigated the role of lipid peroxidation in the pathogenesis of progressive ischemia in a rat burn model. The burn model consisted of a row of four 10 x 20 mm burns separated by three unburned 5 x 20 mm skin bridges (interspaces). The interspaces became ischemic and necrotic by 24 hours, producing a single wound with the merger of the burn sites. U75412E, a lipid peroxidation inhibitor, preserved vascular patency, restored blood flow, prevented a rise in tissue conjugated dienes, and maintained tissue viability in the interspaces. Four separate burn wounds healed between three viable strips of hair-bearing interspaces. The treatment was effective, when given systemically during the period between 2 hours before and 1 hour after the burn. U75412E prevented progressive burn ischemia and the expansion of tissue loss.

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Selected References

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  1. Alexander F., Mathieson M., Teoh K. H., Huval W. V., Lelcuk S., Valeri C. R., Shepro D., Hechtman H. B. Arachidonic acid metabolites mediate early burn edema. J Trauma. 1984 Aug;24(8):709–712. doi: 10.1097/00005373-198408000-00003. [DOI] [PubMed] [Google Scholar]
  2. Braughler J. M., Burton P. S., Chase R. L., Pregenzer J. F., Jacobsen E. J., VanDoornik F. J., Tustin J. M., Ayer D. E., Bundy G. L. Novel membrane localized iron chelators as inhibitors of iron-dependent lipid peroxidation. Biochem Pharmacol. 1988 Oct 15;37(20):3853–3860. doi: 10.1016/0006-2952(88)90066-4. [DOI] [PubMed] [Google Scholar]
  3. Braughler J. M., Pregenzer J. F., Chase R. L., Duncan L. A., Jacobsen E. J., McCall J. M. Novel 21-amino steroids as potent inhibitors of iron-dependent lipid peroxidation. J Biol Chem. 1987 Aug 5;262(22):10438–10440. [PubMed] [Google Scholar]
  4. DeWall R. A., Vasko K. A., Stanley E. L., Kezdi P. Responses of the ischemic myocardium to allopurinol. Am Heart J. 1971 Sep;82(3):362–370. doi: 10.1016/0002-8703(71)90302-4. [DOI] [PubMed] [Google Scholar]
  5. Demling R. H., Katz A., Lalonde C., Ryan P., Jin L. J. The immediate effect of burn wound excision on pulmonary function in sheep: the role of prostanoids, oxygen radicals, and chemoattractants. Surgery. 1987 Jan;101(1):44–55. [PubMed] [Google Scholar]
  6. Demling R. H., LaLonde C. Early postburn lipid peroxidation: effect of ibuprofen and allopurinol. Surgery. 1990 Jan;107(1):85–93. [PubMed] [Google Scholar]
  7. Demling R. H., LaLonde C., Goad M. E. Effect of ibuprofen on the pulmonary and systemic response to repeated doses of endotoxin. Surgery. 1989 Mar;105(3):421–429. [PubMed] [Google Scholar]
  8. Demling R. H., LaLonde C., Liu Y. P., Zhu D. G. The lung inflammatory response to thermal injury: relationship between physiologic and histologic changes. Surgery. 1989 Jul;106(1):52–59. [PubMed] [Google Scholar]
  9. Demling R. H., Lalonde C. Topical ibuprofen decreases early postburn edema. Surgery. 1987 Nov;102(5):857–861. [PubMed] [Google Scholar]
  10. Fowl R. J., Patterson R. B., Gewirtz R. J., Anderson D. K. Protection against postischemic spinal cord injury using a new 21-aminosteroid. J Surg Res. 1990 Jun;48(6):597–600. doi: 10.1016/0022-4804(90)90237-v. [DOI] [PubMed] [Google Scholar]
  11. Im M. J., Manson P. N., Bulkley G. B., Hoopes J. E. Effects of superoxide dismutase and allopurinol on the survival of acute island skin flaps. Ann Surg. 1985 Mar;201(3):357–359. doi: 10.1097/00000658-198503000-00018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. JACKSON D. M. [The diagnosis of the depth of burning]. Br J Surg. 1953 May;40(164):588–596. doi: 10.1002/bjs.18004016413. [DOI] [PubMed] [Google Scholar]
  13. Kaufman T., Neuman R. A., Weinberg A. Is postburn dermal ischaemia enhanced by oxygen free radicals? Burns. 1989 Oct;15(5):291–294. doi: 10.1016/0305-4179(89)90004-1. [DOI] [PubMed] [Google Scholar]
  14. Köller M., König W., Brom J., Erbs G., Müller F. E. Studies on the mechanisms of granulocyte dysfunctions in severely burned patients--evidence for altered leukotriene generation. J Trauma. 1989 Apr;29(4):435–445. doi: 10.1097/00005373-198904000-00004. [DOI] [PubMed] [Google Scholar]
  15. Manson P. N., Anthenelli R. M., Im M. J., Bulkley G. B., Hoopes J. E. The role of oxygen-free radicals in ischemic tissue injury in island skin flaps. Ann Surg. 1983 Jul;198(1):87–90. doi: 10.1097/00000658-198307000-00017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McCord J. M. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med. 1985 Jan 17;312(3):159–163. doi: 10.1056/NEJM198501173120305. [DOI] [PubMed] [Google Scholar]
  17. Mileski W. J., Winn R. K., Vedder N. B., Pohlman T. H., Harlan J. M., Rice C. L. Inhibition of CD18-dependent neutrophil adherence reduces organ injury after hemorrhagic shock in primates. Surgery. 1990 Aug;108(2):206–212. [PubMed] [Google Scholar]
  18. Nishigaki I., Hagihara M., Hiramatsu M., Izawa Y., Yagi K. Effect of thermal injury on lipid peroxide levels of rat. Biochem Med. 1980 Oct;24(2):185–189. doi: 10.1016/0006-2944(80)90010-1. [DOI] [PubMed] [Google Scholar]
  19. Regas F. C., Ehrlich H. P. Elucidating the vascular response to burns with a new rat model. J Trauma. 1992 May;32(5):557–563. doi: 10.1097/00005373-199205000-00004. [DOI] [PubMed] [Google Scholar]
  20. Till G. O., Beauchamp C., Menapace D., Tourtellotte W., Jr, Kunkel R., Johnson K. J., Ward P. A. Oxygen radical dependent lung damage following thermal injury of rat skin. J Trauma. 1983 Apr;23(4):269–277. doi: 10.1097/00005373-198304000-00001. [DOI] [PubMed] [Google Scholar]
  21. Till G. O., Guilds L. S., Mahrougui M., Friedl H. P., Trentz O., Ward P. A. Role of xanthine oxidase in thermal injury of skin. Am J Pathol. 1989 Jul;135(1):195–202. [PMC free article] [PubMed] [Google Scholar]
  22. Till G. O., Hatherill J. R., Tourtellotte W. W., Lutz M. J., Ward P. A. Lipid peroxidation and acute lung injury after thermal trauma to skin. Evidence of a role for hydroxyl radical. Am J Pathol. 1985 Jun;119(3):376–384. [PMC free article] [PubMed] [Google Scholar]
  23. Vasko K. A., DeWall R. A., Riley A. M. Effect of allopurinol in renal ischemia. Surgery. 1972 May;71(5):787–790. [PubMed] [Google Scholar]
  24. Vedder N. B., Fouty B. W., Winn R. K., Harlan J. M., Rice C. L. Role of neutrophils in generalized reperfusion injury associated with resuscitation from shock. Surgery. 1989 Sep;106(3):509–516. [PubMed] [Google Scholar]
  25. Vedder N. B., Winn R. K., Rice C. L., Chi E. Y., Arfors K. E., Harlan J. M. Inhibition of leukocyte adherence by anti-CD18 monoclonal antibody attenuates reperfusion injury in the rabbit ear. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2643–2646. doi: 10.1073/pnas.87.7.2643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ward P. A., Till G. O., Hatherill J. R., Annesley T. M., Kunkel R. G. Systemic complement activation, lung injury, and products of lipid peroxidation. J Clin Invest. 1985 Aug;76(2):517–527. doi: 10.1172/JCI112001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Winn R., Maunder R., Chi E., Harlan J. Neutrophil depletion does not prevent lung edema after endotoxin infusion in goats. J Appl Physiol (1985) 1987 Jan;62(1):116–121. doi: 10.1152/jappl.1987.62.1.116. [DOI] [PubMed] [Google Scholar]

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