Increased lung to blood passage of polyethylene glycols after intratracheal instillation of ferritin and asbestos fibres in the rat.
Urinary recovery of intratracheally instilled polyethylene glycol polymers (PEG:s) in the molecular weight range 722-1294 Da (PEG 1000) was studied under normal conditions and during experimentally induced lung damage in rats. The urinary PEG recoveries were between 30-60% under normal conditions, with a selectivity for smaller PEG:s. No significant differences in the urinary PEG molecular weight profiles were found between 30 days old and adult rats; i.e. they had similar PEG 1162/810 (molecular weights) urinary recovery ratios (0.78 +/- 0.25 and 0.69 +/- 0.27, respectively, p > 0.05). In rats instilled with PEG 1000 and ferritin (5 mg.kg-1 body weight), the urinary recovery was increased for PEG:s with molecular weights greater than 1030 Da; i.e. a higher PEG 1162/810 recovery ratio (1.44 +/- 0.58, p < 0.01) was obtained. Rats instilled with PEG 1000 and crocidolite asbestos fibres (5 mg.kg-1 body weight) showed higher urinary recoveries for PEG:s greater than 854 Da, resulting in a higher PEG 1162/810 ratio (1.47 +/- 0.59, p < 0.01). By adding the iron-chelator, desferrioxamine, to the crocidolite-instillate, the urinary recoveries and the PEG 1162/810 ratio (0.97 +/- 0.47) were reduced, indicating a restored molecular weight selectivity of the lung. Thus, in rats, PEG 1000 passes via the respiratory tract in large amounts which is dependent on the molecular weight. This passage was increased after ferritin- or crocidolite instillation, indicating that the barrier function of the respiratory tract was impaired due to local tissue damage, and that iron may play an important role in this.
Dept of Animal Physiology, University of Lund, Sweden.
H G
HG
Folkesson
P
P
Leanderson
B R
BR
Weström
C
C
Tagesson
D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001194:Asbestos / Q000008:administration & dosage*; D017638:Asbestos, Crocidolite; D001195:Asbestosis / Q000209:etiology / Q000378:metabolism; D015824:Blood-Air Barrier / Q000187:drug effects* / Q000502:physiology; D005293:Ferritins / Q000008:administration & dosage*; D007322:Instillation, Drug; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000032:analysis / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea
D017638:Asbestos, Crocidolite; D001194:Asbestos; D011092:Polyethylene Glycols; D005293:Ferritins