Crosslinked Structure of Polyacrylic Acid Affects Pulmonary Fibrogenicity in Rats
Taisuke Tomonaga, Chinatsu Nishida, Hiroto Izumi, Naoki Kawai, Ke‐Yong Wang, Hidenori Higashi, Jun‐ichi Takeshita, Ryohei Ono, Kazuki Sumiya, Shota Fujii, Yuki Hata, Kazuo Sakurai, Toshiki Morimoto, Yasuyuki Higashi, Kei Yamasaki, Kazuhiro Yatera, Yasuo Morimoto
Abstract
We conducted intratracheal instillations of polyacrylic acid (PAA) with crosslinking and non-crosslinking into rats in order to examine what kinds of physicochemical characteristics of acrylic-acid-based polymers affect responses in the lung. F344 rats were intratracheally exposed to similar molecular weights of crosslinked PAA (CL-PAA) (degree of crosslinking: ~0.1%) and non-crosslinked PAA (Non-CL-PAA) at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months post-exposure. Both PAAs caused increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 6 months following instillation. The release of lactate dehydrogenase (LDH) activity in the BALF was higher in the CL-PAA-exposed groups. Histopathological findings of the lungs demonstrated that the extensive fibrotic changes caused by CL-PAA were also greater than those in exposure to the Non-CL- PAA during the observation period. CL-PAA has more fibrogenicity of the lung, suggesting that crosslinking may be one of the physicochemical characteristic factors of PAA-induced lung disorder.