PI-201

Aim: To investigate the relationship between donor liver cold preservation, lung surfactant (LS) changes and acute lung injury (ALI) after liver transplantation. Methods: Liver transplantation models were established using male Wistar rats. Donor livers were preserved in University of Wisconsin solution at 4 °C for different lengths of time. The effect of ammonium pyrrolidinedithiocarbamate (PDTC) on ALI was also detected. All samples were harvested after 3 h reperfusion. The severity of ALI was evaluated by lung weight/body weight ratio, lung histopathological score, serum nitric oxide (NO) and endothelin (ET)-1 levels, lung tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels. Lung surfactants (LSs) were determined by micellar electrokinetic capillary chromatography. Results: With extended donor liver cold preservation time (CPT), lung histopathological scores, serum ET-1 levels, lung weight/body weight ratio and the level of TNF-α and IL-1β in lung were increased significantly in the 180-min group compared with the sham group (3.16 ± 0.28 vs 1.12 ± 0.21, P < 0.001; 343.59 ± 53.97 vs 141.53 ± 48.48, P < 0.001; 0.00687 ± 0.00037 vs 0.00557 ± 0.00056, P < 0.001; 17.5 ± 3.0 vs 1.3 ± 0.3, P < 0.001; 10.8 ± 2.3 vs 1.8 ± 0.4, P < 0.001), but serum NO levels decreased remarkably (74.67 ± 10.01 vs 24.97 ± 3.18, P < 0.001). The expression of lung phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS) increased when CPT was < 120 min, and decreased when CPT was > 180 min (PC: 1318.89 ± 54.79 vs 1011.18 ± 59.99, P < 0.001; PE: 1504.45 ± 119.96 vs 1340.80 ± 76.39, P = 0.0019; PI: 201.23 ± 34.82 vs 185.88 ± 17.04, P = 0.2265; PS: 300.43 ± 32.95 vs 286.55 ± 55.55, P = 0.5054). All these ALI-associated indexes could be partially reversed by PDTC treatment. Conclusion: Prolonged CPT could induce or inhibit the expression of LSs at the compensation or decompensation stage, and some antioxidants (e.g., PDTC) may reverse the pathological process partially.

Two new platelet aggregation inhibitors, PI-200 and PI-201 were isolated from the fermentation broth of Streptomyces sp. A7498. PI-200 and PI-201 inhibited ADP-induced aggregation of rabbit platelets with an IC50 of 3.8 x 10(-4) M and 7.1 x 10(-4) M, respectively.