A histomorphometric assessment of BHT-induced pulmonary toxicity

The morphological heterogeneity of the lung and the poor extent of knowledge concerning alveolar repair following toxic insult have made morphology, and especially morphometry, a most suitable approach for the study of the injured lung. In this study we aimed to further develop a rapid and quantitative morphological approach to evaluate the sequence of lesion-repair in the aggressed alveolus. Swiss-Webster mice were treated with butylated hydroxytoluene (BHT, 400 mg/kg ip) and the lung was sampled at 1, 3, 5, 7, and 14 d after treatment. A morphometric evaluation, carried out on histological sections, was used to quantify the inflammatory and epithelial regenerative components of the alveolar primary reaction. Classical morphometric parameters such as the Aa and Na ratios, and the mean cellular surface were determined by planimetry. Following BHT administration, the alveolar stem cells (type II pneumocytes) proliferate and differentiate according to a biphasic pattern, with proliferative peaks at d 3 and 7. Furthermore, the challenged pulmonary alveolus retains increased numerical and surface density of macrophages and type II pneumocytes as late as d 14 after initial aggression.