Effects of surface characteristics of potassium titanate whisker samples on acute lung injury induced by a single intratracheal administration in rats.
We compared in vivo biological effects, focusing on lung inflammatory responses after a single intratracheal administration of two types of well-characterized whiskers: potassium octatitanate and potassium hexatitanate, which have similar fiber sizes and chemical compositions, except their surface morphology. The geometrical mean of length (microm), width (microm), and geometric standard deviation (GSD) are: K(2)Ti(8)O(17) (PT1), 6.0[2.0], 0.35[1.51], having rough surface; K(2)Ti(6)O(13) (PT2), 5.0[2.18], 0.31[1.63], having smooth surface. Sixty male Wistar rats (8 wk old) under anesthesia were injected intratracheally with 2 doses of fibers (0.2 mg/0.5 ml/rat, 1.0 mg/0.5 ml/rat) or the same amount of saline solution (group C). Animals were sacrificed on days 1, 3, and 7 after fiber administration, and then the lung tissue and bronchoalveolar lavage (BAL) were collected. There were no obvious differences among the three groups in the yield of BAL fluid. Total protein concentration in BAL increased significantly from day 1; BAL fucose level increased significantly from day 3 in a dose-dependent manner, which gradually recovered by day 7 in groups PT1 and PT2. BAL total protein and fucose in group PT1 increased significantly compared with those in group PT2 at a dose level of 1.0 mg. A dose-independent increase of beta-glucuronidase activity and decrease of superoxide dismutase activity were observed in both fibers. BAL tumor necrosis factor-alpha (TNF-alpha) increased significantly in animals treated with 1.0 mg dosage of PT1 and PT2 on day 1. However, BAL IL-1beta did not show any marked change during the experimental period in animals treated with both fibers. On day 1, BAL cytokine-induced neutrophil attractants (CINC)/growth-related gene product (GRO) increased significantly in the PT1 group treated with 0.2 and 1.0 mg dosage. On day 3, the group treated with 1.0 mg PT1 showed significant increase of CINC/GRO compared with the group treated with 1.0 mg PT2, which recovered to the control level on day 7. Expression of various chemokine mRNAs (MCP-3, MIP-1alpha, RANTES, and eotaxin) increased in rats treated with PT1 or PT2 on day 1 and/or day 3. Increase of gene expression in the PT1 group was greater than that of the PT2 group at 0.2 mg dosage level. These results suggest that differences in the surface morphology of the whisker fibers of similar length and diameter, density, and chemical composition appear to be related to the facilitation of macrophage phagocytes in the macrophage-derived biological effects in acute lung injury induced by inhaled fibers.
Ishihara
Yoko
Y
Department of Hygiene and Public Health (I), School of Medicine, Tokyo Women's Medical University, Tokyo 162-8666, Japan. ishihara@research.twmu.ac.jp
Kyono
Hiroko
H
Kohyama
Norihiko
N
Otaki
Noriko
N
Serita
Fumio
F
Toya
Tadao
T
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000473:pathology*; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008297:Male; D008420:Manufactured Materials; D010586:Phagocytes / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014025:Titanium / Q000009:adverse effects* / Q000737:chemistry; D014132:Trachea / Q000187:drug effects
D016207:Cytokines; C009934:potassium titanate; C021028:potassium octatitanate; D014025:Titanium