Effects of gadolinium chloride on the rat lung following intratracheal instillation.
The metabolic behavior, clearance, and pulmonary effects of gadolinium (Gd), one of the rare earth elements, were investigated after single intratracheal instillation of gadolinium chloride (GdCl3) in male Wistar rats. There was a dose-related increase in Gd content of lung tissue. Gd content in the supernatant of bronchoalveolar lavage fluid (BALF) did not exceed 5 micrograms Gd/BALF even at a dose of 100 micrograms Gd/rat. Gd in the lung tissue decreased very slowly with a biological half-life of 136 days at a dose of 50 micrograms Gd/rat. On the other hand, Gd content in the supernatant of BALF was not detectable after 31 days. These results suggest that intratracheally instilled Gd can be retained in epithelial lining fluid only to a limited extent as soluble forms and is deposited in the lung tissue probably in insoluble forms which are metabolized very slowly. Calcium (Ca) content in BALF increased more rapidly than other toxicological indices such as lactate dehydrogenase activity, protein concentration, and inflammatory cell counts. In the lung tissue, levels of Ca in Gd-instilled groups did not differ from the control value. Although these data suggest that the origin of Ca may be blood plasma, biological and/or toxicological significance of increased Ca is not known. The number of neutrophils reached the maximum at 12 hr after instillation, indicating that Gd has the potency to cause acute lung toxicity. Summarizing the observation, Gd instilled intratracheally into rats was deposited in the lung tissue in nonsoluble forms with an extremely long half-life, while the metal caused a rapid and selective infiltration of serum Ca before acute lung toxicity.
Yoneda
S
S
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Emi
N
N
Fujita
Y
Y
Ohmichi
M
M
Hirano
S
S
Suzuki
K T
KT
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002118:Calcium / Q000097:blood / Q000378:metabolism; D004848:Epithelium / Q000473:pathology; D005682:Gadolinium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D006207:Half-Life; D007442:Intubation, Intratracheal; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007811:Lanthanum / Q000493:pharmacokinetics / Q000633:toxicity; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015019:Yttrium / Q000493:pharmacokinetics / Q000633:toxicity
D015019:Yttrium; D007811:Lanthanum; D005682:Gadolinium; D007770:L-Lactate Dehydrogenase; D002118:Calcium