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Inflammation Research
Published in: Inflammation Research 1/2011

01-01-2011 | Original Research Paper

The effects of lazaroid U-74389G in a rat sepsis model

Authors: Yun-Te Chang, Shue-Ren Wann, Kai-Hseng Hsieh, Yung-Ching Liu, Ching-Hsiung Chang, Mu-Shun Huang, Chun-I Huang, Hong-Tai Chang

Published in: Inflammation Research | Issue 1/2011

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Abstract

Objective and design

To examine the protective effects of a lazaroid, 21-aminosteroid U-74389G, in a rat septic shock model.

Materials or subjects

Male Sprague–Dawley rats (n = 60) aged 6–8 months.

Treatment

Groups were exposed to 500 cGy radiation followed by E. coli inoculation, and either placebo or lazaroid injection (10 mg/kg intraperitoneal) 5 days after irradiation.

Methods

Hemodynamic measurements, arterial blood gases, serum lactate, total antioxidative capacity, and cytokine levels were measured at specific time intervals.

Results

Treatment with the lazaroid U-74389G maintained cardiac output and mean aortic pressure. Lazaroid treatment also prevented the increase in serum lactate seen in placebo-treated rats. Cytokine serum levels in lazaroid-treated rats were not significantly different from those in placebo-treated rats at any time point.

Conclusions

Lazaroid treatment of E. coli-inoculated septic animals lessens the hemodynamic deterioration seen in sepsis.
Literature
1.
Angus DC, Linde-Zwirbe WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of income, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–10.CrossRefPubMed
2.
3.
Vincent JL, Abraham E. The last 100 years of sepsis. Am J Respir Crit Care Med. 2006;173:257–63.CrossRef
4.
Dombrovsky VY, Martin AA, Sunderman J, Paz HL. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med. 2007;35:1244–50.CrossRef
5.
Zhao W, Richardson JS, Momboourquette WeilJA. An in vitro EPR study of the free-radical scavenging actions of the lazaroid antioxidants U-74500A and U-78517F. Free Radic Biol Med. 1995;19:21–30.CrossRefPubMed
6.
Braughler JM, Pregenzer JF, Chase RL, Duncan LA, Jacobsen EJ, McCall JM. Novel 21-aminosteroids as potent inhibitors of iron-dependent lipid peroxidation. J Biol Chem. 1987;262:10438–40.PubMed
7.
Krysztopik RJ, Bentley FR, Spain DA, Wilson MA, Garrison RN. Free radical scavenging by lazaroids improves renal blood flow during sepsis. Surgery. 1996;120:657–62.CrossRefPubMed
8.
Krysztopik RJ, Bentley FR, Spain DA, Wilson MA, Garrison RN. Lazaroid improves intestinal blood flow in the rat during hyperdynamic bacteraemia. Br J Surg. 1997;84:1717–21.CrossRefPubMed
9.
Campo GM, Squadrito F, Altavilla D, Squadrito G, Avenoso A, Canale P, et al. Protection of ischemic and reperfused rat myocardium by the nonglucocorticoid 21-aminosteroid U-74389G, a new inhibitor of lipid peroxidation. J Pharmacol Exp Ther. 1996;277:333–40.PubMed
10.
Duguay P, Chen H, Daloze P, Dumont L. Cardioprotective effects of the lazaroid U74389G following cold preservation and transplantation of rat hearts. Transplantation. 1996;61:1023–8.CrossRefPubMed
11.
Perna AM, Liguori P, Bonacchi M, Laino GM, Nediani C, Fiorillo C, et al. Protection of rat heart from ischaemia-reperfusion injury by the 21-aminosteroid U74389G. Pharmacol Res. 1996;34:25–31.CrossRefPubMed
12.
Takahashi T, Takeyoshi I, Hasegawa Y, Koyano T, Yamagishi T, Oshima K, et al. Cardioprotective effects of lazaroid U-74389G on ischemia-reperfusion injury in canine hearts. J Heart Lung Transplant. 1999;18:285–91.CrossRefPubMed
13.
Wang J, Weil MH, Kamohara T, Tang W, Sun S, Klouche K, et al. A lazaroid mitigates postresuscitation myocardial dysfunction. Crit Care Med. 2004;32:553–8.CrossRefPubMed
14.
Lee KY, Sebastien PG, Zar H, Mueller RA, Boysen PG. Increase in rat plasma antioxidant activity after E.coli lipopolysaccharide administration. Yonsei Med J. 2001;42:114–9.PubMed
15.
Gonder JC, Laber K. A renewed look at laboratory rodent housing and management. ILAR J. 2007;48(1):29–36. (Review).PubMed
16.
Brook I, Walker RI, MacVittie TJ. Effect of antimicrobial therapy on bowel flora and bacterial infection in irradiated mice. Int J Radiat Biol Relat Stud Phys Chem Med. 1988;53(5):709–16.CrossRefPubMed
17.
Fishler M, Cole L, Bond V, Milne W. Therapeutic effect of rat bone marrow injection on rats exposed to lethal whole body X-radiation. Am J Physiol. 1954;177:236–42.PubMed
18.
Brook I, MacVittie TJ, Walker RI. Recovery of aerobic and anaerobic bacteria from irradiated mice. Infect Immun. 1984;46(1):270–1.PubMed
19.
Madonna GS, Ledney GD, Elliott TB, Brook I, Ulrich JT, Myers KR, Patchen ML, Walker RI. Trehalose dimycolate enhances resistance to infection in neutropenic animals. Infect Immun. 1989;57(8):2495–501.PubMed
20.
Elliott TB, Brook I, Stiefel SM. Quantitative study of wound infection in irradiated mice. Int J Radiat Biol. 1990;58(2):341–50.CrossRefPubMed
21.
Griffel MI, Astiz ME, Rackow EC, Weil MH. Effect of mechanical ventilation on systemic oxygen extraction and lactic acidosis during early septic shock in rats. Crit Care Med. 1990;18(1):72–6.CrossRefPubMed
22.
Fang X, Tang W, Sun S, Huang L, Chang YT, Huang Z, Weil MH. Cardiopulmonary resuscitation in a rat model of chronic myocardial ischemia. J Appl Physiol. 2006;101(4):1091–6.CrossRefPubMed
23.
Tseng YM, Lin SK, Hsiao JK, Chen IJ, Lee JH, Wu SH, Tsai LY. Whey protein concentrate promotes the production of glutathione (GSH) by GSH reductase in the PC12 cell line after acute ethanol exposure. Food Chem Toxicol. 2006;44(4):574–8.CrossRefPubMed
24.
Ellrodt AG, Riedinger MS, Kimchi A, Berman DS, Maddahi J, Swan HJ, et al. Left ventricular performance in septic shock: reversible segmental and global abnormalities. Am Heart J. 1985;110:402–9.CrossRefPubMed
25.
Kern KB, Hilwig RW, Rhee KH, Berg RA. Myocardial dysfunction after resuscitation from cardiac arrest: an example of global myocardial stunning. J Am Coll Cardiol. 1996;28:232–40.CrossRefPubMed
26.
Altavilla D, Squadrito F, Campo GM, Squadrito G, Arlotta M, Urna G, Sardella A, et al. The lazaroid, U-74389G, inhibits inducible nitric oxide synthase activity, reverses vascular failure and protects against endotoxin shock. Eur J Pharmacol. 1999;369:49–55.CrossRefPubMed
27.
Gadaletta D, Verma M, Davis JD. Inhibition of neutrophil leukotriene generation by the 21-aminosteroid, U-74389F. J Surg Res. 1994;57:233–7.CrossRef
28.
Semrad SD, Rose ML, Adams JL. Effect of tirilazad mesylate (U74006F) on eicosanoid and tumor necrosis factor generation in healthy and endotoxemic neonatal calves. Circ Shock. 1993;40:235–341.PubMed
29.
Shenkar R, Abraham E. Effects of treatment with the 21-aminosteroid, U74389F, on pulmonary cytokine expression following hemorrhage and resuscitation. Crit Care Med. 1995;23:132–9.CrossRefPubMed
30.
Squadrito F, Altavilla D, Ammendolia L, Squadrito G, Campo GM, Sperandeo A, et al. Improved survival and reversal of endothelial dysfunction by the 21-aminosteroid, U-74389G in splanchnic ischaemia-reperfusion injury in the rat. Br J Pharmacol. 1995;115:395–400.PubMed
31.
Altavilla D, Squadrito F, Serrano M, Campo GM, Squadrito G, Arlotta M, et al. Inhibition of tumour necrosis factor and reversal of endotoxin-induced shock by U83836E, a ‘second generation’ lazaroid in rats. Br J Pharmacol. 1998;124:1293–9.CrossRefPubMed
32.
Neviere R, Fauvel H, Chopin C, Formstecher P, Marchetti P. Caspase inhibition prevents cardiac dysfunction and heart apoptosis in a rat model of sepsis. Am J Respir Crit Care Med. 2001;163:218–25.PubMed
Metadata
Title
The effects of lazaroid U-74389G in a rat sepsis model
Authors
Yun-Te Chang
Shue-Ren Wann
Kai-Hseng Hsieh
Yung-Ching Liu
Ching-Hsiung Chang
Mu-Shun Huang
Chun-I Huang
Hong-Tai Chang
Publication date
01-01-2011
Publisher
SP Birkhäuser Verlag Basel
Published in
Inflammation Research / Issue 1/2011
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-010-0231-3

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