INHIBITORY EFFECTS OF THE DIETARY ANTIOXIDANTS BUTYLATED HYDROXYANISOLE AND BUTYLATED HYDROXYTOLUENE ON BRONCHIOLOALVEOLAR CELL-PROLIFERATION DURING THE BLEOMYCIN-INDUCED PULMONARY FIBROSING PROCESS IN HAMSTERS

The effects of dietary antioxidants on bleomycin (BLM)-induced pulmona ry fibrosis were investigated in Syrian golden hamsters. In addition, the influence on cell proliferative activity in bronchioloalveolar hyp erplastic lesions during the lung fibrosing process was evaluated in t erms of argyrophil nucleolar organizer regions (AgNORs) and proliferat ing cell nuclear antigen (PCNA). Male 6-wk-old hamsters were divided i nto six groups. Groups 1-3 were intratracheally instilled with BLM at a dose of 2.5 U/kg body weight on days 0 and 14, and then given a diet supplemented with 1% butylated hydroxyanisole (BHA), or 1% butylated hydroxytoluene (BHT), or basal diet alone for the following 41 days. G roups 46 were given 1% BHA, 1% BHT or basal diet without BLM treatment for the same time period as that of groups 1-3. The mortality rate of animals in group 1 (BLM/BHA) (one in 20; 5%) was lower than in those of groups 2 (BLM/BHT) (three in 20; 15%) and 3 (BLM alone) (four in 20 ; 20%). BHA and BHT treatments significantly inhibited lung weight gai ns by BLM (P < 0.05). Histopathologically, both BHA and BHT reduced BL M-induced pulmonary histopathological changes such as fibrosis, macrop hage aggregation and epithelial proliferation, with a tendency for cor relation with accumulation of type III collagen. In addition, antioxid ant treatment significantly lowered the mean numbers of AgNORs (P < 0. 01) and PCNA-labelling indices (P < 0.05) in the hyperplastic bronchio loalveolar lesions. The results thus indicate that these antioxidants exert inhibitory effects on proliferation of hyperplastic lesions asso ciated with lung fibrosis. (C) 1996 Elsevier Science Ltd. All rights r eserved.