Advertisement

Curcumin Protects Against Sepsis-Induced Acute Lung Injury in Rats

  • Xuefei Xiao
    Affiliations
    Department of Emergency and Critical are Medicine, the Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China
    Search for articles by this author
  • Mingshi Yang
    Affiliations
    Department of Emergency and Critical are Medicine, the Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China
    Search for articles by this author
  • Dao Sun
    Affiliations
    Department of Emergency and Critical are Medicine, the Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China
    Search for articles by this author
  • Shenghua Sun
    Correspondence
    To whom correspondence and reprint requests should be addressed at Department of Respiratory medicine, the Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, Hunan 410013, People’s Republic of China.
    Affiliations
    Department of Respiratory Medicine, the Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China
    Search for articles by this author
Published:December 26, 2011DOI:https://doi.org/10.1016/j.jss.2011.11.1032
      The present study aimed to investigate the effect of curcumin on sepsis-induced acute lung injury (ALI) in rats, and explore its possible mechanisms. Male Sprague-Dawley rats were randomly divided into the following five experimental groups (n = 20 per group): animals undergoing a sham cecal ligature puncture (CLP) (sham group); animals undergoing CLP (control group); or animals undergoing CLP and treated with vehicle (vehicle group), curcumin at 50 mg/kg (low-dose curcumin [L-Cur] group), or curcumin at 200 mg/kg (high-dose curcumin [H-Cur] group).At 6, 12, 24 h after CLP, blood, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The lung wet/dry weight (W/D) ratio, protein level, and the number of inflammatory cells in the BALF were determined. Optical microscopy was performed to examine the pathologic changes in lungs. Myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, as well as superoxidase dismutase (SOD) activity were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interluekin-8 (IL-8), and macrophage migration inhibitory factor (MIF) were determined in the BALF. Survival rates were recorded at 72 h in the five groups in another experiment. Treatment with curcumin significantly attenuated the CLP-induced pulmonary edema and inflammation, as it significantly decreased lung W/D ratio, protein concentration, and the accumulation of the inflammatory cells in the BALF, as well as pulmonary MPO activity. This was supported by the histopathologic examination, which revealed marked attenuation of CLP-induced ALI in curcumin treated rats. In addition, curcumin significantly increased SOD activity with significant decrease in MDA content in the lung. Also, curcumin caused down-regulation of the inflammatory cytokines TNF-α, IL-8, and MIF levels in the lung. Importantly, curcumin improved the survival rate of rats by 40%–50% with CLP-induced ALI. Taken together, these results demonstrate the protective effects of curcumin against the CLP-induced ALI. This effect can be attributed to curcumin ability to counteract the inflammatory cells infiltration and, hence, ROS generation and regulate cytokine effects.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Surgical Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Schlichting D.
        • McCollam J.S.
        Recognizing and managing severe sepsis: A common and deadly threat.
        South Med J. 2007; 100: 594
        • Ware L.B.
        • Matthay M.A.
        The acute respiratory distress syndrome.
        N Engl J Med. 2000; 342: 1334
        • Windsor A.C.
        • Mullen P.G.
        • Fowler A.A.
        Acute lung injury: What have we learned from animal models?.
        Am J Med Sci. 1993; 306: 111
        • Andrews P.
        • Azoulay E.
        • Antonelli M.
        • et al.
        Year in review in intensive care medicine, 2005. II. Infection and sepsis, ventilator- associated pneumonia, ethics, hematology and hemostasis, ICU organization and scoring, brain injury.
        Intensive Care Med. 2006; 32: 380
        • Diekema D.J.
        • Pfaller M.A.
        • Jones R.N.
        • 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.
        Clin Infect Dis. 1999; 29: 595
        • Slutsky A.S.
        • Tremblay L.N.
        Multiple system organ failure. Is mechanical ventilation a contributing factor?.
        Am J Respir Crit Care Med. 1998; 157: 1721
        • Ammon H.P.
        • Walh M.A.
        Pharmacology of Curcuma longa.
        Planta Med. 1991; 57: 1
        • Treves R.
        • Maheu E.
        • Dreiser R.L.
        Therapeutic trials in digital osteoarthritis. A critical review.
        Rev Rhum Engl Ed. 1995; 62: 33S
        • Habtemariam S.
        Anti-inflammatory activity of the anti-rheumatic herbal drug, gravel root (Eupatorium purpureum): Further biological activities and constituents.
        Phytother Res. 2001; 15: 687
        • Gescher A.
        Polyphenolic phytochemicals versus non-steroidal anti-inflammatory drugs: Which are better cancer chemopreventive agents?.
        J Chemother. 2004; 16: 3
        • Shoelson S.E.
        • Lee J.
        • Goldfine A.B.
        Inflammation and insulin resistance.
        J Clin Invest. 2006; 116: 1793
        • Sharma R.A.
        • Gescher A.J.
        • Steward W.P.
        Curcumin: The story so far.
        Eur J Cancer. 2005; 41: 1955
        • Lukita-Atmadja W.
        • Ito Y.
        • Baker G.L.
        • et al.
        Effect of curcuminoids as anti-inflammatory agents on the hepatic microvascular response to endotoxin.
        Shock. 2002; 17: 399
        • Memis D.
        • Hekimoglu S.
        • Sezer A.
        • et al.
        Curcumin attenuates the organ dysfunction caused by endotoxemia in the rat.
        Nutrition. 2008; 24: 1133
        • Sun J.
        • Yang D.
        • Li S.
        • et al.
        Effects of curcumin or dexamethasone on lung ischaemia-reperfusion injury in rats.
        Eur Respir J. 2009; 33: 398
        • Su X.
        • Wang L.
        • Song Y.
        • et al.
        Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide.
        Intensive Care Med. 2004; 30: 133
        • Aggarwal B.B.
        • Sung B.
        Pharmacological basis for the role of curcumin in chronic diseases: An age-old spice with modern targets.
        Trend Pharmacol Sci. 2009; 30: 85
        • Abraham E.
        Neutrophils and acute lung injury.
        Crit Care Med. 2003; 31: S195
        • Macdonald J.
        • Galley H.F.
        • Webster N.R.
        Oxidative stress and gene expression in sepsis.
        Br J Anaesth. 2003; 90: 221
        • Bhattacharyya J.
        • Biswas S.
        • Datta A.G.
        Mode of action of endotoxin: Role of free radicals and antioxidants.
        Curr Med Chem. 2004; 11: 359
        • Suntres Z.E.
        • Shek P.N.
        Prophylaxis against lipopolysaccharide-induced acute lung injury by α-tocopherol liposomes.
        Crit Care Med. 1998; 26: 723
        • Kinnula V.L.
        • Crapo J.D.
        Superoxide dismutases in the lung and human lung diseases.
        Am J Respir Crit Care Med. 2003; 167: 1600
        • Giebelen I.A.
        • van Westerloo D.J.
        • LaRosa G.J.
        • et al.
        Local stimulation of α7 cholinergic receptors inhibits LPS-induced TNF-α release in the mouse lung.
        Shock. 2007; 28: 700
        • Carney D.E.
        • Lutz C.J.
        • Picone A.
        • et al.
        Soluble tumor necrosis factor receptor prevents post-pump syndrome.
        J Surg Res. 1999; 83: 113
        • Literat A.
        • Su F.
        • Norwicki M.
        • et al.
        Regulation of proinflammatory cytokine expression by curcumin in hyaline membrane disease (HMD).
        Life Sci. 2001; 70: 253
        • Kunkel S.L.
        • Standiford T.
        • Kasahara K.
        • et al.
        Interleukin-8 (IL-8): The major neutrophil chemotactic factor in the lung.
        Exp Lung Res. 1991; 17: 17
        • Wessely-Szponder J.
        The influence of TNFα and IL-8 on secretory action of neutrophils isolated from heifers in the course of bovine respiratory disease.
        Acta Vet Hung. 2008; 56: 187
        • Liu K.
        • Shen L.
        • Wang J.
        • et al.
        The preventative role of curcumin on the lung inflammatory response induced by cardiopulmonary bypass in rats.
        J Surg Res. 2012; 174: 73
        • Biswas S.K.
        • McClure D.
        • Jimenez L.A.
        • et al.
        Curcumin induces glutathione biosynthesis and inhibits NF-κB activation and interleukin-8 release in alveolar epithelial cells: Mechanism of free radical scavenging activity.
        Antioxid Redox Signal. 2005; 7: 32
        • Bernhagen J.
        • Calandra T.
        • Mitchell R.A.
        • et al.
        MIF is a pituitary-derived cytokine that potentiates lethal endotoxemia.
        Nature. 1993; 365: 756
        • Beishuizen A.
        • Thijs L.G.
        • Haanen C.
        • et al.
        Macrophage migration inhibitory factor and hypothalamo-pituitary-adrenal function during critical illness.
        J Clin Endocrinol Metab. 2001; 86: 2811
        • Baugh J.A.
        • Bucala R.
        Macrophage migration inhibitory factor.
        Crit Care Med. 2002; 30: S27
        • Donnelly S.C.
        • Haslett C.
        • Reid P.T.
        • et al.
        Regulatory role for macrophage migration inhibitory factor in acute respiratory distress syndrome.
        Nat Med. 1997; 3: 320

      Linked Article

      • Curcumin for the Prevention of Acute Lung Injury in Sepsis: Is It More Than the Flavor of the Month?
        Journal of Surgical ResearchVol. 176Issue 1
        • Preview
          Curcumin is found in the popular spice turmeric, which is a member of the ginger family. It gives curry its bright yellow color and it is even used as a food color [1]. It has been used for thousands of years as a Chinese and Indian herbal medication [2]. Curcumin has long been known to have anti-inflammatory properties since the 1950s, especially in murine models. Tham and co-workers demonstrated that a curcuminoid substance reduced the lethality in induced abdominal sepsis in mice [3]. The mechanism might be due to up-regulation of peroxisome proliferator-activated receptor (PPAR)-gamma, an anti-inflammatory nuclear receptor.
        • Full-Text
        • PDF