Biochemical and Histological Alterations in Rats after Acute Nitrogen Dioxide Intoxication

Abstract

<jats:p> 1 In previous studies a rat inhalation model was developed to investigate the treatment of acute nitrogen dioxide (NO<jats:sub>2</jats:sub>) intoxication. </jats:p><jats:p> 2 Biochemical parameters, which may be important for the evaluation of lung injury and repair, were reviewed and compared with the histology. </jats:p><jats:p> 3 After exposure to high NO<jats:sub>2</jats:sub> concentrations (75 ppm, 125 ppm or 175 for 10 min) <jats:sup>1</jats:sup> the lung injury observed by light microscope was most pronounced after 24 h and became worse with increasing concentration. </jats:p><jats:p> 4 The most sensitive indicators for lung injury in the broncho-alveolar lavage fluid (BAL) were protein and albumin concentrations, angiotensin converting enzyme activity, β-glucuronidase activity and the presence of neutrophil leucocytes. The changes observed in these variables were dose-dependent. Following exposure to 175 ppm the protein and albumin concentrations and the angiotensin converting enzyme activity showed a 100-fold increase, while the β-glucuronidase activity showed a 10-fold increase. </jats:p><jats:p> 5 Glucose-6-phosphate dehydrogenase and glutathione peroxidase in the supernatant of lung homogenate and gamma-glutamyl transferase activity in BAL are likely to be the most practical parameters for monitoring the phase of repair because their activities were maximal at the moment histological changes were reduced in intensity. </jats:p><jats:p> 6 Repair was almost complete 7 d following exposure. </jats:p>

Effect of oxidant air pollutants on the respiratory system: insights from experimental animal research

“…A macroscopic consequence of oedema formation after exposure to these two oxidants consists of increased lung volume and wet weight [32,76,77,81]. A sensitive index of lung oedema, which constitutes a common finding after exposure both to NO 2 and O 3 , is the presence of serum proteins in the bronchoalveolar lavage fluid [82][83][84][85]. Alteration of epithelial and vascular permeability leading to oedema is particularly marked at small airway and alveolar levels [75,[85][86][87][88].…”

“…Morphological observations show mainly focal interstitial and intra-alveolar oedema [75,87], with the former more pronounced around arteries than airways or veins [89]. A strong correlation has been found between the degree of NO 2 or O 3 exposure and the amount of oedema observed both in the alveolar spaces [88,89] and in peribronchiolar and perivascular tissue [81,84,89]. Oedema is more evident at an early stage of exposure [75,90], but has also been reported after long-term exposure [78]; it reverses after cessation of exposure [84,87,88].…”

“…Tracheal permeability develops immediately after exposure to oxidant gases [83][84][85][86][87][88][103][104][105][106] and reaches a peak at 8 h postexposure, whilst the number of polymorphonuclear leucocytes usually peaks at 12 h [103]. Rats rendered leukopenic with cyclophosphamide have a significant reduction in circulating and pulmonary leucocytes and in airway permeability induced by O 3 , and pretreatment with either the LTD 4 antagonist FPL55712 or indomethacin also inhibits the O 3 -induced increase in permeability [104].…”

“…Indeed, the stimulation of the glutathione peroxidase system and of other protective enzymes, such as superoxide dismutase, disulphide reductase and 6-phosphogluconate dehydrogenase, is a response to short-or medium-term exposure to oxidants [65,84,91,101,116,122,123]. By contrast, this antioxidative protective enzymatic system is inhibited after long-term exposure to low levels of NO 2 [117].…”

No Beneficial Effect of N-acetylcysteine Treatment on Broncho-alveolar Lavage Fluid Variables in Acute Nitrogen Dioxide Intoxicated Rats

“…A loading dose of 85 mg kg -1 h -1 or 170 mg kg -1 h -1 was followed by a continuous infusion (until autopsy) with a dose of 225 mg kg -1 24 h -1 or 450 mg kg -1 24 h -1 respectively. 3 Twenty four hours after exposure to 175 ppm NO 2 (1 ppm is 1.88 mg m -3 ) for 10 min, NAC did not reduce the increase of variables in bronchoalveolar lavage fluid which reflect the severity of lung damage. 4 The protein and albumin concentration and the activities of angiotensin converting enzyme and alkaline phosphatase in broncho-alveolar lavage fluid after NO 2 exposure were even more Introduction .…”