Anti-inflammatory effect of the conjugate of superoxide dismutase with the copolymer of divinyl ether and maleic anhydride against rat re-expansion pulmonary edema

Bovine erythrocyte superoxide dismutase (SOD) was conjugated with the copolymer of divinyl ether and maleic anhydride, known as DIVEMA or pyran copolymer. The DM–SOD conjugate was resistant against the proteolytic enzymes in serum, and showed a prolonged half-life in vivo after intravenous injection. DM–SOD was applied for the treatment of rat lung edema caused by the re-expansion after the left bronchus has been clipped for 3 days. The anti-inflammatory effect was evaluated by the inhibition rate of the water content due to the edema. Neither SOD nor DIVEMA reduced the increase in water content in the lung, whereas DM–SOD could effectively protect against the increase in water content such that the water content of the re-expanded lung was the same as that of the control right lung. Using electron microscopic observation the difference between the SOD and DM–SOD treatment in the water swelling of the interalveolar septum was clearly indicated. Observation of the surface of the endothelial wall in the blood vessel of the lung showed more a drastic difference. The leukocyte attachment on the endothelial layer observed following the treatment with SOD was not observed following that with DM–SOD. This observation indicates that DM–SOD had stopped the inflammation process at the first step of leukocyte adhesion, which should be followed by the rolling and expansion of the leukocytes to initiate the normal inflammation process.