title: The in vitro synthesis and degradation of prostaglandins during the development of bleomycin-induced pulmonary fibrosis in hamsters.
abstract: Subsequent to optimization of conditions for enzyme assay, we examined the in vitro synthesis and degradation of prostaglandins by the lung during the development 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 PGD2 was significantly elevated to 10.2, 10.8, and 12.5 nmoles/lung at 7, 21 and 28 days, respectively, as compared to the control value of 5.6 nmoles/lung. Significant increases in PGF2 alpha synthesis from the control value of 3.3 nmoles/lung to 5.2, 8.2 and 5.5 nmoles/lung were found at 4, 7 and 21 days post-treatment, respectively. The synthesis of PGE2 also showed significant increases above the control value of 6.1 nmoles/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-PGF1 alpha was significantly increased to 7.4, 7.5 and 8.6 nmoles/lung at 7, 21 and 28 days post-treatment, respectively, as compared to the control value of 4.4 nmoles/lung. The synthesis of TxB2 was also significantly increased from the control value of 3.9 nmoles/lung to 7.5 and 6.4 nmoles/lung at 7 and 21 days post-treatment, respectively. Accompanying the increased synthesis of prostaglandins in general, the in vitro degradation of PGF2 alpha was significantly increased from the control value of 71.1 nmoles/lung to 173.5, 131.7 and 143.3 nmoles/lung 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 inflammatory response and resident cellular proliferation.
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001761:Bleomycin; D006224:Cricetinae; D015237:Dinoprost; D015232:Dinoprostone; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D008861:Microsomes / Q000378:metabolism; D015230:Prostaglandin D2; D011453:Prostaglandins / Q000096:biosynthesis*; D011457:Prostaglandins D / Q000096:biosynthesis; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D011506:Proteins / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D013929:Thromboxane B2 / Q000096:biosynthesis
chemical_list: D011453:Prostaglandins; D011457:Prostaglandins D; D011458:Prostaglandins E; D011460:Prostaglandins F; D011506:Proteins; D001761:Bleomycin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D015232:Dinoprostone; D015230:Prostaglandin D2