The effects of dietary
antioxidants on
bleomycin (BLM)-induced
pulmonary fibrosis were investigated in Syrian golden hamsters. In addition, the influence on cell proliferative activity in bronchioloalveolar hyperplastic lesions during the lung fibrosing process was evaluated in terms of argyrophil nucleolar organizer regions (
AgNORs) and
proliferating cell nuclear antigen (
PCNA). Male 6-wk-old hamsters were divided into 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. Groups 4-6 were given 1%
BHA, 1%
BHT or basal diet without BLM treatment for the same time period as that in those 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 gains by BLM (P < 0.05). Histopathologically, both
BHA and
BHT reduced BLM-induced pulmonary histopathological changes such as
fibrosis, macrophage aggregation and epithelial proliferation, with a tendency for correlation with accumulation of
type III collagen. In addition,
antioxidant treatment significantly lowered the mean numbers of
AgNORs (P < 0.01) and
PCNA-labelling indices (P < 0.05) in the hyperplastic bronchioloalveolar lesions. The results thus indicate that these
antioxidants exert inhibitory effects on proliferation of hyperplastic lesions associated with lung
fibrosis.