This study analyzes the sepsis healing therapeutic potential of carnosine against experimentally sepsis-induced male albino rats. Carnosine in 2 different doses, 25 mg/kg and 50 mg/kg, were administered for 30 consecutive days. At the end of the treatment, lipid peroxidation, catalase, superoxide dismutase, glutathione peroxidase and myeloperoxidase activities were measured. Lungs weight and total protein content were determined in the bronchoalveolar fluid (BALF). Cytokines such as macrophage inhibitory factor (MIF), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-α) were determined in the BALF. In addition, the histopathological analysis was also carried out to understand the effect of carnosine in the cellular architecture. Carnosine treatment significantly renormalized the lipid peroxidation and other antioxidant enzymes. IL-β, TNF-α, and MIF were found to be reduced after carnosine treatment. After carnosine treatment, the intensity of sepsis was significantly reduced evidenced by histopathological analysis. In western blot analysis, carnosine treatment causes the upregulation of IκBα together with the downregulation of the expressions of p65 and p-IKKα/β (Ser 180/Ser 181).

1.
Schlichting D, McCollam JS: Recognizing and managing severe sepsis: a common and deadly threat. South Med J 2007;100:594-600.
2.
Ware LB, Matthay MA: The acute respiratory distress syndrome. N Engl J Med 2000;342:1334-1349.
3.
Windsor AC, Mullen PG, Fowler AA: Acute lung injury: what have we learned from animal models? Am J Med Sci 1993;306:111-116.
4.
Gulewitsch Wl, Amiradžibi S: Ueber das Carnosin, eine neue organische Base des Fleischextractes. Ber Dtsch Chem Ges 1900;33:1902-1903.
5.
Aruoma OI, Laughton MJ Halliwell B: Carnosine, homocarnosine and anserine: Could they act as antioxidants in vivo? Biochem J 1989;264:863-869.
6.
Choi SY, Kwon HY, Kwon OB, Kang JH: Hydrogen peroxide-mediated Cu, Zn-superoxide dismutase fragmentation: protection by carnosine, homocarnosine and anserine. Biochim Biophys Acta 1999;1472:651-657.
7.
Klebanov GI, Teselkin YuO, Babenkova IV, Lyubitsky OB, Rebrova OYu, Boldyrev AA, Vladimirov YuA: Effect of carnosine and its components on free-radical reactions. Membr cell biol 1998;12:89-99.
8.
Babizhayev MA, Seguin MC, Gueyne J, Evstigneeva RP, Ageyeva EA, Zheltukhina GA: L-carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) act as natural antioxidants with hydroxyl-radical-scavenging and lipid-peroxidase activities. Biochem J 1994;304:509-516.
9.
Karton A, O'Reilly RJ, Pattison DI, Davies MJ, Radom L: Computational design of effective, bioinspired HOCl antioxidants: the role of intramolecular Cl+ and H+ shifts. J Am Chemi Soc 2012;134:19240-1945.
10.
Chan KM, Decker EA: Endogenous skeletal muscle antioxidants. Crit Rev Food Sci Nutr 1994;34:403-426.
11.
Kohen R, Yamamoto Y, Cundy KC, Ames BN: Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain. Proc Natl Acad Sci U S A 1988;85:3175-3179.
12.
Vistoli G, De Maddis D, Cipak A, Zarkovic N, Carini M, Aldini G: Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation. Free Radic Res 2013;47:3-27.
13.
Reddy VP, Garrett MR, Perry G, Smith MA: Carnosine: a Versatile Antioxidant and antiglycating agent. Sci Aging Knowledge Environ 2005;18:pe12.
14.
Diekema DJ, Pfaller MA, Jones RN, et al: Survey of bloodstream infections due to gram-negative bacilli: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, and Latin America for the SENTRY antimicrobial surveillance program, 1997. Clin Infect Dis 1999;29:595-607.
15.
Umrani RD, Paknikar KM: Zinc oxide nanoparticles show antidiabetic activity in streptozotocin-induced type1 and 2 diabetic rats. Nanomedicine (Lond) 2014;9:89-104.
16.
Weydert CJ, Cullen JJ: Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc 2009;5:51-66.
17.
Pulli B, Ali M, Forghani R, Schob S, Hsieh KL, Wojtkiewicz G, Linnoila JJ, Chen JW: Measuring myeloperoxidase activity in biological samples. PLoS One 2013;8:e67976.
18.
Giebelen IA, van Westerloo DJ, LaRosa GJ, et al: Local stimulation of alpha7 cholinergic receptors inhibits LPS-induced TNF-alpha release in the mouse lung. Shock 2007;28:700-703.
19.
Carney DE, Lutz CJ, Picone A, et al: Soluble tumor necrosis factor receptor prevents post-pump syndrome. J Surg Res 1999;83:113-121.
20.
Literat A, Su F, Norwicki M, et al: Regulation of pro-inflammatory cytokine expression by curcumin in hyaline membrane disease (HMD). Life Sci 2001;70:253-267.
21.
Kunkel SL, Standiford T, Kasahara K, et al: Interleukin-8 (IL-8): the major neutrophil chemotactic factor in the lung. Exp Lung Res 1991;17:17-23.
22.
Wessely-Szponder J: The influence of TNFalpha and IL-8 on secretory action of neutrophils isolated from heifers in the course of bovine respiratory disease. Acta Vet Hung 2008;56:187-196.
23.
Biswas SK, McClure D, Jimenez LA, et al: Curcumin induces glutathione biosynthesis and inhibits NF-kappaB activation and interleukin-8 release in alveolar epithelial cells: mechanism of free radical scavenging activity. Antioxid Redox Signal 2005;7:32-41.
24.
Bernhagen J, Calandra T, Mitchell RA, et al: MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature 1993;365:756-759.
25.
Baugh JA, Bucala R: Macrophage migration inhibitory factor. Crit Care Med 2002;30:S27-S35.
26.
Abraham E: Neutrophils and acute lung injury. Crit Care Med 2003;31:S195-S199.
27.
Bhattacharyya J, Biswas S, Datta AG: Mode of action of endotoxin: role of free radicals and antioxidants. Curr Med Chem 2004;11:359-368.
28.
Suntres ZE, Shek PN: Prophylaxis against lipopolysaccharide-induced acute lung injury by alpha-tocopherol liposomes. Crit Care Med 1998;26:723-729.
29.
Kinnula VL, Crapo JD: Superoxide dismutases in the lung and human lung diseases. Am J Respir Crit Care Med 2003;167:1600-1619.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.