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Exp Biol Med (Maywood) ; 242(1): 8-21, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27550926

ABSTRACT

The interstitial lung diseases are poorly understood and there are currently no studies evaluating the association of physical exercise with an ACE2 activator (DIZE) as a possible treatment for this group of diseases. We evaluate the effects of pharmacological treatment with an angiotensin-converting enzyme 2 activator drug, associated with exercise, on the pulmonary lesions induced by bleomycin. From the 96 male Balb/c mice used in the experiment, only 49 received 8 U/kg of bleomycin (BLM, intratracheally). The mice were divided into control (C) and bleomycin (BLM) groups, sedentary and trained (C-SED, C-EXE, BLM-SED, BLM-EXE), control and bleomycin and also sedentary and trained treated with diminazene (C-SED/E, C-EXE/E, BLM-SED/E, BLM-EXE/E). The animals were trained five days/week, 1 h/day with 60% of the maximum load obtained in a functional capacity test, for four weeks. Diminazene groups were treated (1 mg/kg, by gavage) daily until the end of the experiment. The lungs were collected 48 h after the training program, set in buffered formalin and investigated by Gomori's trichrome, immunohistochemistry of collagen type I, TGF-ß1, beta-prolyl-4-hydroxylase, MMP-1 and -2. The BLM-EXE/E group obtained a significant increase in functional capacity, reduced amount of fibrosis and type I collagen, decreased expression of TGF-ß1 and beta-prolyl-4-hydroxylase and an increase of metalloproteinase -1, -2 when compared with the other groups. The present research shows, for the first time, that exercise training associated with the activation of ACE2 potentially reduces pulmonary fibrosis.


Subject(s)
Diminazene/pharmacology , Peptidyl-Dipeptidase A/metabolism , Physical Conditioning, Animal/physiology , Pulmonary Fibrosis/therapy , Angiotensin-Converting Enzyme 2 , Animals , Collagen Type I/metabolism , Disease Models, Animal , Lung/drug effects , Lung/metabolism , Lung/pathology , Male , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 2/metabolism , Mice, Inbred BALB C , Physical Endurance/drug effects , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/physiopathology
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