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12 week old Sprague Dawley rats males and females

By Tierre Miller posted 30 days ago

  

12 week old Sprague Dawley rats, males & females

SIGNALMENT:
12 week old Sprague Dawley rats, males & females

HISTORY:
Rats were given a novel investigative compounds (imadazole derivatives) orally for up to 10 days. Labored breathing and deaths were observed at higher doses on days 6-8.

GROSS PATHOLOGY:
Some rats showed clear fluid in thoracic cavity, lungs appeared red and heavy.

    What's Your Diagnosis? Provide your possible etiologies in the comment section below. Member login is required to comment.

    r118a.jpg

    Treated, H&E, 20x obj. Rat #1. Edema, alveolar and perivascular.

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    Treated, H&E, 20x obj. Rat #2. Edema, perivascular with mononuclear inflammation and hemorrhage.
    r118d.jpg

    Treated, H&E, 20x obj. Rat #2. Degeneration, fibrinous of alveolar walls with mononuclear inflammation.

    r118d.jpg

    Treated, H&E, 40x obj. Rat#2. Degeneration, fibrinous of alveolar walls with hemorrhage.

    r118d.jpg
    Treated, H&E, 20x obj. Rat #3. Hyperplasia, alveolar type II cells. Inflammation, mononuclear.
    r118d.jpg
    Treated, H&E, 40x, obj. Rat #4. Inflammation, granulomatous.
    r118d.jpg
    Treated, H&E, 40x obj. Rat#4. Inflammation, eosinophilic with goblet cell hyperplasia.
    r118d.jpg
    Confocal microscopy. 20x obj. Cells stained with a specific fluorescent dye to detect superoxide generation in the presence or absence of the compound.

    MORPHOLOGIC DIAGNOSI(E)S AND ETIOLOGY: 

    1. Lung: Pulmonary edema, hemorrhage, fibrinoid degeneration of alveolar walls with mononuclear inflammation.
    2. Lung: Alveolar type II cell hyperplasia, granulomatous/eosinophilic inflammation with goblet cell hyperplasia.

    Etiology: These changes were induced by imidazole compounds. The potentially reactive region is an NH group on the core ring. Though these compounds produce pulmonary lesions similar to paraquat, they are structurally different.

    CONTRIBUTOR: Anonymous

    CONTRIBUTOR'S COMMENTS: 
    Pulmonary edema and fibrinoid degeneration of alveolar walls are reminiscent of compounds causing oxidative damage to the lung, such as paraquat. Paraquat however is a dipyridilium compound and structurally different. Degenerative changes were widespread and seen mainly at higher doses while alveolar type II cell hyperplasia and granulomatous/eosinophilic inflammation with goblet cell hyperplasia were focal lesions seen in rats that survived to study end.

    Flowcytometric assays on a series of compounds using A549 cells, a type-II human alveolar epithelial cell line, confirmed a significant correlation between the potential to induce oxidative stress and the manifestation of pulmonary lesions.

    In this assay, if superoxide (O2-) is produced on exposure to the compound, it is detected using - hydroethidine (HE), a sodium borohydride-reduced form of ethidium bromide (EB). HE, a specific and sensitive indicator of O2-, is cell-permeable and can be directly oxidised to EB by O2- produced by the cell.

    REFERENCES:

    1. Gopinath, C., Prentice, D.E., Lewis, D.J. Atlas of Experimental Toxicologiocal Pathology. MTP Press Limited, Lancaster, UK, pp. 22-42, 1987.
    2. Vijeyaratnam, G.S., Corrin, B. Experimental paraquat poisoning: a histological and electron-optical study of the changes in the lung. J. Pathol. 103:123-129, 1971.

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