The [formula omitted] synthesis and degradation of prostaglandins during the development of bleomycin-induced pulmonary fibrosis in hamsters 1−3

Abstract

Subsequent to optimization of conditions for enzyme assay, we examined the in vitro synthesis and degradation of prostaglandins by the lung during the devel opment of bleomycin-induced pulmonary fibrosis in hamsters. It was found that the microsomal protein content on a per lung basis was significantly increased to 144, 129, 134, and 121% of control (2.3 mg protein/lung) at 4, 7, 14 and 21 days post-treatment, respectively. The synthesis of PGD 2 was significantly elevated to 10.2, 10.8, and 12.5 moles/lung at 7, 21 and 28 days, respectively, as compared to the control value of 5.6 moles/lung. Significant increases in PGF synthesis from the control value of 3.3 moles/lung to 5.2, 8.2 and 5.5 moles/lung were found at 4, 7 and 21 days post-treatment, respectively. The synthesis of PGE 2 also showed significant increases above above the control value of 6.1 moles/lung to 10.5, 12.2 and 11.0 nmoles/lung at 7, 21 and 28 days post-treatment, respectively. Similarly, the synthesis of 6-keto-PGF was significantly increased to 7.4, 7.5 and 8.6 moles/lung at 7, 21 and 28 days post-treatment, respectively, as compared to the control value of 4.4 moles/lung. The synthesis of TxB was also significantly increased from the control value of 3.9 nmoles/lung to 7.5 and 6.4 moles/lung at 7 and 21 days post-treatment, respectively. Accompanying the increased synthesis of prostaglandins in general, the in vitro degradation of PGF was significantly increased from the control v of 71.1 nmoles/lung to 173.5, 131.7 and 143.3 nmoles/lung at at 2, 4 and 7 days after bleomycin treatment, respectively. We conclude that bleomycin-induced pulmonary fibrosis leads to changes in prostaglandin synthesis and degradation possibly as a result of an accompanying inflammatorv response and resident cellular oroliferation.