Protection by methylprednisolone against butylated hydroxytoluene-induced pulmonary damage and impairment of microsomal monooxygenase activities in the mouse: lack of effect on fibrosis

Abstract

The effects of the synthetic corticosteroid methylprednisolone (MP; 30 mg/kg, s.c. given twice daily for 3 days), on the pneumotoxic effects of a single dose of butylated hydroxytoluene (BHT; 400 mg/kg, i.p.) over a 10 day experimental period was investigated in male C57BL/6N mice. BHT alone caused time-dependent alveolar hypercellularity, inflammatory infiltration, alveolar septal thickening and hypercellularity of the bronchiolar epithelium, reaching a maximum by day 5 with some degree of recovery by day 10. The pulmonary monooxygenase activities reflected the degree of alveolar damage and Clara cell abnormality with time; reductions in monooxygenase activities occurred and minimum levels (7-15% of control) were reached by day 5 and again a trend towards recovery by day 10. MP administered 0, 24 and 48 hr after BHT treatment partially protected mice from these effects of BHT in a distinctly time-dependent fashion; the degree of protection decreased as the time between BHT challenge and MP treatment increased. Although MP alone did not morphologically affect Clara and alveolar cells, it increased, decreased or had no effect on the monooxygenase activities. About 25% of the mice that received BHT alone died by day 5 and 50% by day 10. MP completely blocked the lethal effects of BHT by day 5 and reduced the deaths to between 15% and 25% by day 10. Interestingly, MP did not protect against the BHT-induced pulmonary fibrosis, measured as total lung hydroxyproline content, irrespective of the time between BHT challenge and MP treatment. MP alone did not cause any deaths nor increase lung hydroxyproline content.