Epidemiological and experimental studies have suggested that diesel exhaust particles (DEPs), which generate reactive oxygen species, may be involved in the recent increase in the prevalence of lung diseases. Cacao liquor proanthocyanidins (CPs) are naturally occurring polyphenols with antioxidative activities. We carried out a study in mice to investigate the effects of dietary supplementation of CPs on lung injury induced by intratracheal administration of DEPs (500 μg/body). Dietary supplementation with 1.0% CPs inhibited DEP-induced lung injury, characterized by neutrophil sequestration and edema. Immunohistochemical analyses showed that CPs prevented enhanced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 caused by DEPs in the lung injury. Numerous adducts of nitrotyrosine, N-(hexanonyl) lysine, 4-hydroxy-2-nonenal, and 8-OHdG were also observed immunohistochemically in the lungs of mice treated with DEPs. However, these indicators of oxidative stress were barely visible in mice pretreated with CP supplementation. In addition, the level of thiobarbituric acid reactive substances in the lung was decreased by CP supplementation in the presence of DEPs. These results suggest that CPs inhibit DEP-induced lung injury by reducing oxidative stress, in association with a reduction in the expression of adhesion molecules.
SalviSSNordenhallCBlombergARudellBPourazarJKellyFJWilsonSSandstromTHolgateSTFrewAJ. Acute exposure to diesel exhaust increases IL-8 and GRO-alpha production in healthy human airways. Am J Respir Crit Care Med2000; 161:550–61.
2.
DockeryDWPopeCA3rdXuXSpenglerJDWareJHFayMEFerrisBGJrSpeizerFE. An association between air pollution and mortality in six U.S. cities. N Engl J Med1993; 329:1753–64.
3.
SarnatJASchwartzJCatalanoPJSuhHH. Gaseous pollutants in particulate matter epidemiology: confounders or surrogates?Environ Health Perspect2001; 109:1053–58.
4.
NicolaiT. Environmental air pollution and lung disease in children. Monaldi Arch Chest Dis1999; 54:475–88.
5.
SegalaCFaurouxBJustJPascualLGrimfeldANeukirchF. Short-term effect of winter air pollution on respiratory health of asthmatic children in Paris. Eur Respir J1998; 11:677–81.
6.
McClellanRO. Health effects of exposure to diesel exhaust particles. Annu Rev Pharmacol Toxicol1987; 27:279–89.
7.
IchinoseTFuruyamaASagaiM. Biological effects of diesel exhaust particles (DEP). II. Acute toxicity of DEP introduced into lung by intratracheal instillation. Toxicology1995; 99:153–71.
8.
SagaiMFuruyamaAIchinoseT. Biological effects of diesel exhaust particles (DEP). III. Pathogenesis of asthma like symptoms in mice. Free Radic Biol Med1996; 21:199–211.
9.
TakanoHYoshikawaTIchinoseTMiyabaraYImaokaKSagaiM. Diesel exhaust particles enhance antigen-induced airway inflammation and local cytokine expression in mice. Am J Respir Crit Care Med1997; 156:36–49.
10.
MiyabaraYTakanoHIchinoseTLimHBSagaiM. Diesel exhaust enhances allergic airway inflammation and hyperresponsiveness in mice. Am J Respir Crit Care Med1998; 157:1138–45.
11.
TakanoHIchinoseTMiyabaraYYoshikawaTSagaiM. Diesel exhaust particles enhance airway responsiveness following allergen exposure in mice. Immunopharmacol Immunotoxicol1998; 20:329–38.
12.
TakanoHLimHBMiyabaraYIchinoseTYoshikawaTSagaiM. Manipulation of the L-arginine-nitric oxide pathway in airway inflammation induced by diesel exhaust particles in mice. Toxicology1999; 139:19–27.
13.
SagaiMSaitoHIchinoseTKodamaMMoriY. Biological effects of diesel exhaust particles. I. In vitro production of superoxide and in vivo toxicity in mouse. Free Radic Biol Med1993; 14:37–48.
14.
LimHBIchinoseTMiyabaraYTakanoHKumagaiYShimojyoNDevaliaJLSagaiM. Involvement of superoxide and nitric oxide on airway inflammation and hyperresponsiveness induced by diesel exhaust particles in mice. Free Radic Biol Med1998; 25:635–46.
15.
KumagaiYArimotoTShinyashikiMShimojoNNakaiYYoshikawaTSagaiM. Generation of reactive oxygen species during interaction of diesel exhaust particle components with NADPH-cytochrome P450 reductase and involvement of the bioactivation in the DNA damage. Free Radic Biol Med1997; 22:479–88.
16.
TakanoHYanagisawaRIchinoseTSadakaneKInoueKYoshidaSTakedaKYoshinoSYoshikawaTMoritaM. Lung expression of cytochrome P450 1A1 as a possible biomarker of exposure to diesel exhaust particles. Arch Toxicol2002; 76:146–59.
OsakabeNYamagishiMSanbongiCNatsumeMTakizawaTOsawaT. The antioxidative substances in cacao liquor. J Nutr Sci Vitaminol (Tokyo)1998; 44:313–21.
20.
HammerstoneJFLazarusSAMitchellAERuckerRSchmitzHH. Identification of procyanidins in cocoa (Theobroma cacao) and chocolate using high-performance liquid chromatography/mass spectrometry. J Agric Food Chem1999; 47:490–98.
21.
NatsumeMOsakabeNYasudaABabaSTokunagaTKondoKOsawaTTeraoJ. In vitro antioxidative activity of (−)-epicatechin glucuronide metabolites present in human and rat plasma. Free Radic Res2004; 38:1341–53.
22.
BabaSOsakabeNYasudaANatsumeMTakizawaTNakamuraTTeraoJ. Bioavailability of (−)-epicatechin upon intake of chocolate and cocoa in human volunteers. Free Radic Res2000; 33:635–47.
23.
NatsumeMOsakabeNYamagishiMTakizawaTNakamuraTMiyatakeHHatanoTYoshidaT. Analyses of polyphenols in cacao liquor, cocoa, and chocolate by normal- phase and reversed-phase HPLC. Biosci Biotechnol Biochem2000; 64:2581–90.
24.
KatoYMiyakeYYamamotoKShimomuraYOchiHMoriYOsawaT. Preparation of a monoclonal antibody to N(epsilon)-(Hexanonyl)lysine: application to the evaluation of protective effects of flavonoid supplementation against exercise-induced oxidative stress in rat skeletal muscle. Biochem Biophys Res Commun2000; 274:389–95.
25.
KatoYKawakishiSAokiTItakuraKOsawaT. Oxidative modification of tryptophan residues exposed to peroxynitrite. Biochem Biophys Res Commun1997; 234:82–89.
26.
TakanoHYanagisawaRIchinoseTSadakaneKYoshinoSYoshikawaTMoritaM. Diesel exhaust particles enhance lung injury related to bacterial endotoxin through expression of proinflammatory cytokines, chemokines, and intercellular adhesion molecule-1. Am J Respir Crit Care Med2002; 165:1329–37.
27.
LeeKSLeeHKHayflickJSLeeYCPuriKD. Inhibition of phosphoinositide 3-kinase delta attenuates allergic airway inflammation and hyperresponsiveness in murine asthma model. Faseb J2006; 20:455–63.
28.
LundbergAHGrangerNRussellJCallicuttSGaberLWKotbMSabekOGaberAO. Temporal correlation of tumor necrosis factor-alpha release, upregulation of pulmonary ICAM-1 and VCAM-1, neutrophil sequestration, and lung injury in diet-induced pancreatitis. J Gastrointest Surg2000; 4:248–60.
29.
SwarupVGhoshJGhoshSSaxenaABasuA. Antiviral and anti-inflammatory effects of rosmarihic acid in an experimental murine model of Japanese encephalitis. Antimicrob Agents Chemother2007; 51:3367–78.
30.
ChaeYJKimCHHaTSHeschelerJAhnHYSachinidisA. Epigallocatechin-3-O-gallate inhibits the angiotensin II-induced adhesion molecule expression in human umbilical vein endothelial cell via inhibition of MAPK pathways. Cell Physiol Biochem2007; 20:859–70.
31.
BabaSOsakabeNNatsumeMYasudaAMutoYHiyoshiTTakanoHYoshikawaTTeraoJ. Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans. Eur J Nutr2004; 44:1–9.
32.
BaiYSuzukiAKSagaiM. The cytotoxic effects of diesel exhaust particles on human pulmonary artery endothelial cells in vitro: role of active oxygen species. Free Radic Biol Med2001; 30:555–68.
33.
HiuraTSKaszubowskiMPLiNNelAE. Chemicals in diesel exhaust particles generate reactive oxygen radicals and induce apoptosis in macrophages. J Immunol1999; 163:5582–93.
34.
IchinoseTTakanoHMiyabaraYYanagisawaRSagaiM. Murine strain differences in allergic airway inflammation and immunoglobulin production by a combination of antigen and diesel exhaust particles. Toxicology1997; 122:183–92.
35.
ArimotoTYoshikawaTTakanoHKohnoM. Generation of reactive oxygen species and 8-hydroxy-2′-deoxyguanosine formation from diesel exhaust particle components in L1210 cells. Jpn J Pharmacol1999; 80:49–61.
36.
TokiwaHSeraNNakanishiYSagaiM. 8-Hydroxyguanosine formed in human lung tissues and the association with diesel exhaust particles. Free Radic Biol Med1999; 27:1251–59.
37.
ReiterCDTengRJBeckmanJS. Superoxide reacts with nitric oxide to nitrate tyrosine at physiological pH via peroxynitrite. J Biol Chem2000; 275:32460–71.
38.
BeckmanJSKoppenolWH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol1996; 271:C1424–32.
39.
IschiropoulosH. Biological tyrosine nitration: a pathophysiological function of nitric oxide and reactive oxygen species. Arch Biochem Biophys1998; 356:1–11.
40.
RaoKMMaJYMeighanTBargerMWPackDVallyathanV. Time course of gene expression of inflammatory mediators in rat lung after diesel exhaust particle exposure. Environ Health Perspect2005; 113:612–22.
41.
YasudaANatsumeMOsakabeN. Radical scavenging activities of procyanidins in Theobroma cacao. Sci Report of Meiji Seika Kaisha2001; 40:42–51.
42.
AdamsonGELazarusSAMitchellAEPriorRLCaoGJacobsPHKremersBGHammerstoneJFRuckerRBRitterKASchmitzHH. HPLC method for the quantification of procyanidins in cocoa and chocolate samples and correlation to total antioxidant capacity. J Agric Food Chem1999; 47:4184–97.
43.
LotitoSBActis-GorettaLRenartMLCaligiuriMReinDSchmitzHHSteinbergFMKeenCLFragaCG. Influence of oligomer chain length on the antioxidant activity of procyanidins. Biochem Biophys Res Commun2000; 276:945–53.
44.
TakizawaHOhtoshiTKawasaki'SKohyamaTDesakiMKasamaTKobayashiKNakaharaKYamamotoKMatsushimaKKudohS. Diesel exhaust particles induce NF-kappa B activation in human bronchial epithelial cells in vitro: importance in cytokine transcription. J Immunol1999; 162:4705–14.
45.
WhitekusM.J.LiNZhangMWangMHorwitzMANelsonSKHorwitzLDBrechunNDiaz-SanchezDNelAE. Thiol antioxidants inhibit the adjuvant effects of aerosolized diesel exhaust particles in a murine model for ovalbumin sensitization. J Immunol2002; 168:2560–72.
46.
KuhnauJ. The flavonoids. A class of semi-essential food components: their role in human nitrition. Wld Rev Nutr Diet1976; 24:117–25.
47.
HertogMGFeskensEJHollmanPCKatanMBKromhoutD. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet1993; 342:1007–19.
