PATHOLOGICAL STUDIES ON THE EFFICACY OF VITAMIN C AND N-ACETYLCYSTEINE AGAINST THE FIBROGENIC EFFECT OF BLEOMYCIN IN ALBINO RATS -LUNG

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Abstract

Forty two adult male Wistar albino rats were randomized into 7 groups, each consisting of 6 animals to evaluate the efficacy of vitamin C and N-Acetylcysteine (NAC) against the pulmonary fibrosis induced by bleomycin. group (1) was the saline-treated control group. Animals in group (2) were treated with bleomycin (15 mg/kg B. wt., i.p). Rats in group (3) received 50 mg vitamin C/kg B.wt. Each rat in group (4) was given 300 mg NAC /kg B.wt. Each rat in group (5) was simultaneously given similar doses of bleomycin and vitamin C as those given to groups (2&3). Each rat in group (6) was simultaneously given similar doses of bleomycin and NAC as those given to groups (2&4). Each rats in group (7) was simultaneously given similar doses of bleomycin, vitamin C and NAC as those given to groups (2&3&4). All treatments were given three times a week for a total period of 4 weeks. The lungs of bleomycin group showed several pneumonic areas replaced the lung tissue and were represented by intense aggregations of neutrophils with focal alveolar liquefaction. These areas were also showed osseous metaplasia. Thickening of interalveolar septa by edema , extravasated erythrocytes and huge numbers of neutrophils was detected. Sometimes, the alveolar spaces were stuffed with eosinophilic edematous fluid and leukocytes. Perivascular edema and round cells and polymorphs infiltrations were detected. Peribronchial blood vessels showed narrowing and thickening of its wall by hyperplasia of tunica media. Other showed focal calcification of their catarrhal bronchitis and the others were obliterated by desquamated epithelium and leukocytes (bronchiolitis obliterans). Multifocal thickening of the alveolar wall with fibroblast proliferation, collagen formation and round cells infiltrations were visualized. The fibrous tissue in the pneumonic areas was gradually invaded the interstitial tissue inducing pulmonary fibrosis with collapsed alveoli. The collagen was confirmed by Masson-trichrome stain. Moreover, the alveoli were focally stuffed by foamy macrophages. The aforementioned lesions of bleomycin were lowered with administration of each vitamin C or NAC alone and restored to the normal with simultaneous administration of both drugs. It could be concluded that the bleomycin in Wistar rats induces pulmonary injury and fibrosis. Both vitamin C and NAC are effective in amelioration of pulmonary fibrosis and injury induced by bleomycin. NAC is proved to be an excellent drug and is more potent than vitamin C, where the lesions of bleomycin were lowered. Furthermore, the histological evidence supported that the simultaneous administration of vitamin C and NAC are more protective than each one alone, where the lesions were restored to the normalwall. Most of bronchi showed.
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