This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Shengjun Wang Articles by Witten, M. L. Search for Related Content PubMed PubMed Citation Articles by Shengjun Wang, Articles by Witten, M. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Antioxidants Lung Diseases Social Bookmarking                         What's this?

Early Alterations of Lung Injury Following Acute Smoke Exposure and 21-Aminosteroid Treatment

Department of Pediatrics, University of Arizona, Tucson, Arizona 85724

R. Clark Lantz

Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona, 85724, Center for Toxicology, University of Arizona, Tucson, Arizona 85724

Raymond F. Robledo

Department of Pediatrics, University of Arizona, Tucson, Arizona 85724, Center for Toxicology, University of Arizona, Tucson, Arizona 85724

Veronica Breceda

Department of Pediatrics, University of Arizona, Tucson, Arizona 85724

Allison M. Hays

Department of Pediatrics, University of Arizona, Tucson, Arizona 85724

Mark L. Witten

Department of Pediatrics, University of Arizona, Tucson, Arizona 85724, Center for Toxicology, University of Arizona, Tucson, Arizona 85724, mwitten{at}peds.arizona.edu.

In a simulated fire-related smoke exposure protocol, New Zealand white rabbits were utilized to investigate the potential effects of the 21-aminosteroid (lazaroid) analog U75412E on the early events of acute lung injury. Inhalation of a total of 1.6 mg/kg U75412E aerosolized at a rate of 1.53 mg/min at 0.5 hr after smoke exposure significantly attenuated the extent of lung injury at 1 hr, as evidenced by decreased bronchoalveolar lavage (BAL) concentration of total protein, 6-keto-prostaglandin F₁-, and blood gas defect. Histopathologic examination demonstrated that the lazaroid significantly attenuated smoke-induced lung injury as evidenced by a decrease in wet lung/body weight ratio, necrosis, and sloughing of airway epithelial cells. Electron microscopy showed that the lazaroid decreased smoke-induced interstitial edema and the vacuolization of alveolar type II epithelium (21.6 ± 9.7 vs 8.5 ± 3.6 vacuoled blebs/cell, smoke only vs smoke + lazaroid). However, U75412E did not attenuate smoke-induced changes in BAL concentration of tumor necrosis factor-, total cell count, and granulocyte percentage. These observations suggest that U75412E may exert its action through cooperative mechanisms, such as the modulation of arachidonic acid metabolism, in addition to its characterized antioxidative effects.

Key Words: Lazaroids • tumor necrosis factor- • prostaglandin • gas exchange • respiratory epithelium

References

• Aeba R., Killinger WA, Keenan RJ, Yousem SA, Hamamoto I., Hardesty RL, and Griffith BP (1992). Lazaroid U74500A as an additive to University of Wisconsin solution for pulmonary grafts in the rat transplant model. J. Thorac. Cardiovasc. Surg. 104: 1333-1339.[Abstract]
• Audus KL, Guillot FL, and Braughler JM (1991). Evidence for 21-aminosteroid association with the hydrophobic domains of brain microvessel endothelial cells. Free Radical Biol. Med. 11: 361-371.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Bidani A., Wang CZ, and Heming TA (1996). Early effects of smoke inhalation on alveolar macrophage functions. Burns 22: 101-106.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Braughler JM, Chase RL, Neff GL, Yonkers PA, Day JS, Hall ED, Sethy VH, and Lahti RA (1988). A new 21-aminosteroid antioxidation lacking glucocorticoid activity stimulates adrenocorticotropin secretion and blocks arachidonic acid release from mouse pituitary tumor (AtT-20) cells. J. Pharmacol. Exp. Ther. 244: 423-427.[Abstract/Free Full Text]
• Braugher JM and Hall ED (1989). Central nervous system trauma and stroke: I. Biochemical considerations for oxygen radicals formation and lipid peroxidation [Review]. Free Radical Biol. Med. 6: 289-301.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Braughler JM, Pregenzer JF, Chase RL, Duncan LA, Jacobsen EJ, and McCall JM (1987). Novel 21-amino steroids as potent inhibitors of iron-dependent lipid peroxidation. J. Biol. Chem. 262: 10438-10440.[Abstract/Free Full Text]
• Brown M., Desai M., Traber LD, Herndon DN, and Traber DL (1988). Dimethylsulfoxide with heparin in the treatment of smoke inhalation injury. J. Burn Care Rehabil. 9: 22-25.[Medline] [Order article via Infotrieve]
• Clark WR and Fromm BS (1987). Burn mortality: Experience at a regional burn unit: Literature review. Acta Chir. Scand. Suppl. 537: 1-126.[Medline] [Order article via Infotrieve]
• Eskandari MK, Nguyen DT, Kunkel SL, and Remick DG (1990). WEHI 164 subclone 13 assay for TNF: Sensitivity, specificity, and reliability. Immunol. Invest. 19: 69-79.[Web of Science][Medline] [Order article via Infotrieve]
• Espevik T. and Nissen-Meyer J. (1986). A highly sensitive cell line, WEHI 164 subclone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes. J. Immunol. Methods 95: 99-105.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Griffin RL, Krzesicki RF, Fidler SF, Rosenbloom CL, Auchampach JA, Manning AM, Haas JV, Cammarata SK, Chin JE, and Richards IM (1994). Attenuation of oxidant-induced lung injury by 21-aminosteroids (lazaroids): Correlation with the mRNA expression for E-selectin, P-selectin, ICAM-1, and VCAM-1. Environ. Health Perspect. 102(suppl. 10): 193-200.
• Hall ED, McCall JM, and Means ED (1994). Therapeutic potential of the lazaroids (21-aminosteroids) in acute central nervous system trauma, ischemia and subarachnoid hemorrhage [Review]. Adv. Pharmacol. 28: 221-268.[Medline] [Order article via Infotrieve]
• Harwood B. and Hall JR (1989). What kills in fires: Smoke inhalation or burns. Fires J. 83: 28-34.
• Heppler JS, Witten ML, and Lantz RC (1995). Morphological alterations of rabbit terminal bronchiole epithelium subjected to acute smoke injury and lazaroid U75412E. Am. J. Respir. Crit. Care Med. 151: A173.
• Huang JZ, Yang Z., Wang Z., and Leng H. (1996). Study on characteristics of blast-fragment combined injury in dogs. J. Trauma 40: S63-S67.[Web of Science][Medline] [Order article via Infotrieve]
• Huang SH, Leonard S., Shi X., Goins MR, and Vallyathan V. (1998). Antioxidant activity of lazaroid (U-75412E) and its protective effects against crystalline silica-induced cytotoxicity. Free Radical Biol. Med. 24: 529-536.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Johnson D., Hurst T., Prasad K., Wilson T., Saxena A., Murphy F., and Mayers I. (1994). Lazaroid pretreatment preserves gas exchange in endotoxin-treated dogs. J. Crit. Care Med. 9: 213-223.[CrossRef]
• Krzanowski JJ (1994). Oxidant-induced alterations of lung sufactant system. J. Fla. Med. Assoc. 81: 49-51.[Medline] [Order article via Infotrieve]
• Lantz RC, Chen GJ, Wang S., and Witten ML (1995). Protective effects of inhaled lazaroid (U75412E) in a model of smoke-induced lung injury. FASEB J. 9: A572.
• Linares HA, Herndon DN, and Traber DL (1989). Sequence of morphologic events in experimental smoke inhalation. J. Burn Care Rehabil. 10: 27-37.[Medline] [Order article via Infotrieve]
• McLaughlin GE and Frank L. (1994). Effects of the 21-aminosteroid, U74389F, on bleomycin-induced pulmonary fibrosis in rats. Crit. Care Med. 22: 313-319.[Web of Science][Medline] [Order article via Infotrieve]
• Miniati M., Cocci F., Monti S., Filippi E., Sarnelli R., Ferdeghini M., Gattai V., and Pistolesi M. (1996). Lazaroid U-74389F attenuates phorbol ester-induced lung injury in rabbits. Eur. Respir. J. 9: 758-764.[Abstract]
• Morganroth ML, Till GO, Schoeneich S., and Ward PA (1988). Eicosanoids are involved in the permeability changes but not the pulmonary hypertension after systemic activation of complement. Lab. Invest. 58: 316-323.[Web of Science][Medline] [Order article via Infotrieve]
• Oulton MR, Janigan DT, MacDonald Jmr, Faulker GT, and Scott JE (1994). Effects of smoke inhalation on alveolar surfactant subtypes in mice. Am. J. Pathol. 145: 941-950.[Abstract]
• Pinkerton KE and Crapo JD (1985). Morphometery of the alveolar region of the lung. In: Toxicology of Inhaled Materials, HP Witschi and JD Brain (eds). Springer-Verlag, New York, pp.259-285.
• Rider ED, Witten ML, Lantz RC, Hays AM, and Dizon-Co L. (1993). A free radical scavenger (lazaroid U75412E) prevents smoke inhalation-induced changes in alveolar surfactant phospholipids. Am. Rev. Respir. Dis. 147: A363.
• Shelley SA (1994). Oxidant-induced alterations of lung sufactant system. J. Fla. Med. Assoc. 81: 49-51.[Medline] [Order article via Infotrieve]
• Shenkar R. and Abraham E. (1995). Effects of treatment with the 21-aminosteroid, U74389F, on pulmonary cytokine expression following hemorrhage and resuscitation. Crit. Care Med. 23: 132-139.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Tanigaki T., Suzuki Y., Heimer D., Sussman HH, Ross WG, and Raffin TA (1993). Attenuation of acute injury and oxygen radical production by 21-aminosteroid, U-78518F. J. Appl. Physiol. 74: 2155-2160.[Abstract/Free Full Text]
• Thomas PD, Mao GD, Rabinovitch A., and Poznansky MJ (1993). Inhibition of superoxide-generating NADPH oxidase of human neutrophils by lazaroids (21-aminosteroids and 2-methylaminochromans). Biochem. Pharmacol. 45: 241-251.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Thompson PB, Herndon DN, Abston S., and Rutan T. (1987). Effect of early excision on patients with major thermal injury. J. Trauma 27: 205-207.[Web of Science][Medline] [Order article via Infotrieve]
• Thompson PB, Herndon DN, Traber DL, and Abston S. (1986). Effects on mortality of inhalation injury. J. Trauma 26: 163-165.[Web of Science][Medline] [Order article via Infotrieve]
• Traber DL, Herndon DN, and Stein MD (1986). The pulmonary lesion of smoke inhalation in an ovine model. Circ. Shock 18: 311-323.[Web of Science][Medline] [Order article via Infotrieve]
• Wang S., Lantz RC, Chen GJ, Breceda V., Rider E., Hays AM, Parliman G., Tollinger B., Rolledo RF, Kunke K., Tinajero J., and Witten ML (1996). The prophylactic effects of U75412E pretreatment in a smoke-induced lung injury rabbit model. Pharmacol. Toxicol. 79: 231-237.[Web of Science][Medline] [Order article via Infotrieve]
• Wang S., Lantz RC, Rider ED, Chen GJ, Breceda V., Hays AM, Tollinger B., Rolledo RF, and Witten ML (1997). A free radical scavenger (lazaroid U75412E) attenuates TNF- generation in a rabbit model of smoke induced lung injury. Respiration 64: 358-363.[Web of Science][Medline] [Order article via Infotrieve]
• Wheeler AP, Hardie WD, and Bernard GR (1992). The role of cyclooxygenenase products in lung injury induced by tumor necrosis factor in sheep. Am. Rev. Respir. Dis. 145: 632-639.[Web of Science][Medline] [Order article via Infotrieve]
• Witten ML, Grad R., Quan SF, Sobonya RE, Hubbard AK, Lantz RC, Lentz LA, Devine LC, and Lemen RJ (1990). Piriprost pretreatment attenuates the smoke-induced increase in 99mTcDTPA lung clearance. Exp. Lung Res. 16: 339-353.[Web of Science][Medline] [Order article via Infotrieve]
• Witten ML, Lantz RC, Grad R., Seidner S., Hubbard AK, Quan SF, and Lemen RJ (1991). Effect of smoke inhalation on immediate changes in lung chemical mediators. Res. Commun. Chem. Pathol. Pharmacol. 74: 259-272.[Web of Science][Medline] [Order article via Infotrieve]
• Witten ML, Lemen RJ, Quan SF, Sobonya RE, Roseberry H., Stevenson JL, and Clayton JRC (1985). Acute cigarette smoke exposure increases alveolar permeability in rabbits. Am. Rev. Respir. Dis. 132: 321-325.[Web of Science][Medline] [Order article via Infotrieve]

Toxicologic Pathology, Vol. 27, No. 3, 334-341 (1999)
DOI: 10.1177/019262339902700309


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Shengjun Wang Articles by Witten, M. L. Search for Related Content PubMed PubMed Citation Articles by Shengjun Wang, Articles by Witten, M. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Antioxidants Lung Diseases Social Bookmarking                         What's this?