Inhibition of post-ischemic reperfusion injury of the kidney by diamine oxidase.

To elucidate the role of histamine in the pathogenesis of post-ischemic reperfusion injury of tissues, the effect of diamine oxidase (DAO) was studied on the changes in renal functions induced by 30 min occlusion followed by reperfusion of the renal vessels of unilaterally nephrectomized rats. Kinetic analysis using radiolabeled albumin revealed that vascular permeability of the kidney increased markedly after reperfusion. Although the intensity of neutrophil-dependent chemiluminescence of the blood remained unchanged during the occlusion, it increased significantly after reperfusion. Histological examination revealed a marked degeneration of glomeruli and proximal tubules in the reperfused kidney. Transtubular transport of phenolsulfophthalein (PSP) decreased markedly after reperfusion with concomitant increase in plasma levels of creatinine. Intravenously administered DAO markedly inhibited the reperfusion-induced increase in vascular permeability, preserved the structure of the kidney and normalized the rate of clearance of PSP and creatinine. Combined use of diphenylhydramine and ranitidine also inhibited the reperfusion injury of the kidney. These results suggested that histamine and its receptors might play critical roles in post-ischemic reperfusion injury of the kidney.