Comparison of two quantitative methods of discerning airspace enlargement in smoke-exposed mice.

In this work, we compare two methods for evaluating and quantifying pulmonary airspace enlargement in a mouse model of chronic cigarette smoke exposure. Standard stereological sample preparation, sectioning, and imaging of mouse lung tissues were performed for semi-automated acquisition of mean linear intercept (L(m)) data. After completion of the L(m) measurements, D(2), a metric of airspace enlargement, was measured in a blinded manner on the same lung images using a fully automated technique developed in-house.

Pulmonary inflammation in mice exposed to mainstream cigarette smoke.

Male C57Bl/6 (C57) and ICR mice were exposed by nose-only inhalation to mainstream cigarette smoke (MS) from 2R4F reference cigarettes, at concentrations of 75, 250, and 600 microg of total particulate matter (TPM) per liter, for up to 6 mo. Respiratory-tract tissue (nose, larynx, and lung), blood, and bronchoalveolar lavage fluid (BALF) samples were collected and analyzed at several time points. Blood samples were analyzed for biomarkers of exposure (COHb and nicotine).

Upper respiratory tract lesions in inhalation toxicology.

This paper describes some important differences in normal histology of the upper respiratory tract of laboratory animals. It also provides examples of lesions observed or reported in the upper respiratory tract of laboratory animals, predominantly rodents, exposed via inhalation. The anatomy and physiology of upper respiratory tract tissues play a major role in the response to an insult, given that different epithelial types vary in susceptibility to injury and toxicant exposure concentrations throughout the airway vary due to airflow dynamics.

3-week inhalation exposure to cigarette smoke and/or lipopolysaccharide in AKR/J mice.

AKR/J mice were exposed to cigarette smoke (CS) and/or lipopolysaccharide (LPS) via inhalation for 3 wk and pulmonary responses were evaluated. The objective was to explore the feasibility of coexposing LPS with cigarette smoke under a subacute exposure, as a surrogate for viral or bacterial insults, that would mimic the pathogenesis of infection-related chronic obstructive pulmonary disease (COPD) exacerbations. The study was the first step in an effort to develop a rodent COPD model in which morphologic lesions of COPD develop in a shorter period of exposure and more closely simulate human COPD.

Alpha 2u-globulin nephropathy and carcinogenicity following exposure to decalin (decahydronaphthalene) in F344/N rats.

Decalin (decahydronaphthalene) is a widely used industrial solvent known to cause male rat-specific alpha2u-globulin nephropathy. In this project, 13-week and two-year inhalation studies of decalin were conducted consecutively in both sexes of F344/N rats. The key objectives were to (1) characterize the 13-week toxicity of decalin in rats, with an emphasis on nephropathy in males; (2) compare the kidney concentrations of decalin, 2-decalone, and alpha2u-globulin in males over 2 to 13 weeks of decalin exposure; and (3) correlate male rat nephropathy observed in the 13-week study with renal carcinogenicity in the two-year study.