title: Influence of experimental type 1 diabetes on the pulmonary effects of diesel exhaust particles in mice.
abstract: Epidemiologically, exposure to particulate air pollution is associated with increases in morbidity and mortality, and diabetics are especially vulnerable to effects of particles. This study was carried out to determine the respiratory effect of diesel exhaust particles (DEP; 0.4mg/kg) on mice rendered diabetic by the injection of streptozotocin or vehicle (control). Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4mg/kg) or saline. 24h later, the measurement of airway reactivity to methacholine in vivo by a forced oscillation technique showed a significant and dose-dependent increase in airway resistance in non-diabetic mice exposed to DEP versus non-diabetic mice exposed to saline. Similarly, the airway resistance was significantly increased in diabetic mice exposed to DEP versus diabetic mice exposed to saline. Nevertheless, there was no difference in the airway resistance between diabetic and non-diabetic mice after i.t. administration of DEP. Following DEP administration there were neutrophil polymorphs infiltration of pulmonary interalveolar septae and the alveolar spaces with many macrophages containing DEP in both diabetic and non-diabetic mice. Interestingly, apoptotic cells were only found in the examined lung sections from diabetic mice exposed to DEP. Total proteins and albumin concentrations in bronchoalveolar lavage (BAL) fluid, markers for increase of epithelial permeability, were significantly increased in diabetic mice exposed to DEP compared to saline-treated diabetic and DEP-treated non diabetic mice. Superoxide dismutase activity and reduced glutathione concentration in BAL were significantly decreased in diabetic mice exposed to DEP compared to saline-treated diabetic and DEP-treated non diabetic mice. Moreover, tumor necrosis factor α (TNFα) concentrations were significantly increased in diabetic mice exposed to DEP compared to saline-treated diabetic and DEP-treated non diabetic mice. We conclude that, at the dose and time point investigated, DEP equally increased airway resistance and caused infiltration of inflammatory cells in the lung of both diabetic and non-diabetic mice. However, the occurrence of oxidative stress, the presence lung apoptotic cells and the increase of total proteins, albumin and TNFα in BAL fluid were only seen in DEP-exposed diabetic mice suggesting an increased respiratory susceptibility to particulate air pollution.
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates. anemmar@hotmail.com
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Nemmar
authors.forename: Suhail
authors.initials: S
authors.lastname: Al-Salam
authors.forename: Deepa
authors.initials: D
authors.lastname: Subramaniyan
authors.forename: Javed
authors.initials: J
authors.lastname: Yasin
authors.forename: Priya
authors.initials: P
authors.lastname: Yuvaraju
authors.forename: Sumaya
authors.initials: S
authors.lastname: Beegam
authors.forename: Badreldin H
authors.initials: BH
authors.lastname: Ali
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001985:Bronchial Provocation Tests / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005978:Glutathione / Q000378:metabolism; D006651:Histocytochemistry; D015850:Interleukin-6 / Q000378:metabolism; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D052638:Particulate Matter / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D015850:Interleukin-6; D052638:Particulate Matter; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; D013482:Superoxide Dismutase; D005978:Glutathione