Abstract
The effects of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), on bleomycin-induced diffuse alveolar damage (DAD) were investigated in male Syrian golden hamsters. Six-week-old animals were treated with a single intratracheal administration of bleomycin (BLM; 5mg/5ml/kg) or an equivalent volume of saline. Starting 1 day after the treatment, animals were given 1% BHA or 1% BHT in the diet or basal diet alone for 31 days. The survival rate of the BLM/BHA group (55%) was significantly higher than that of the BLM alone (15%) or BLM/BHT (15%) groups (p<0.01). Histopathologically, the lungs of hamsters in the BLM alone group, which were found dead 1 week after the treatment, showed severe pulmonary edema with hemorrhage. These were clearly attenuated by the BHA treatment, which in addition, somewhat accelerated fibrosing and regenerative changes. Moreover, surviving animals in the BLM/BHA group showed a tendency for reduction of emphysematous changes as compared to those receiving BLM alone and consequently to retain the normal alveolar architecture. On the other hand, the BHT administration did not exert any apparent inhibitory effects on early alveolar damage. Our results thus clearly indicate that BHA exerts a protective effect on BLM-induced DAD in hamsters although BHT did not inhibit the lung injury under the present experimental conditions. Possible mechanisms for the differences in influence between BHA and BHT on BLM-induced DAD are discussed.