Plasma elimination kinetics and renal handling of copper/zinc superoxide dismutase in the rat

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Abstract
The renal handling of bovine and human superoxide dismutase (SOD) was investigated in Sprague-Dawley and Munich-Wistar rats. Under normal physiological conditions the half-time of the major rapid component of the plasma elimination curve was estimated at 6.0 +/- 0.5 min, the volume of distribution at 35.7 +/- 3.3 ml kg-1, i.e. the plasma volume and the corresponding plasma clearance at 4 ml min-1 kg-1. After a single intravenous dose, most of the enzyme was distributed to and eliminated by the two kidneys, whereas the non-renal clearance was low, 0.5 ml min-1 kg-1. The single nephron filtration of SOD, as assessed from micropuncture of Bowman's space, was 10.4 +/- 1.0 nl min-1, which was 26 +/- 2% of that for inulin. The total elimination of SOD by glomerular filtration would thereby be 2.5 ml min-1 kg-1, i.e. the glomerular ultrafiltration process would account for the largest part of the elimination of SOD from circulating plasma. After the dosage of 20 mg kg-1, about two-thirds of the injected SOD was excreted as the intact molecule into the urine, whereas one-third was found to be reabsorbed and metabolized by the proximal tubular epithelial cells. In animals suffering from unilateral post-ischaemic acute renal failure, the elimination half-time was 13 +/- 1.9 min, a value which increased by 55 +/- 5 min after bilateral functional nephrectomy. By contrast, the distribution volume remained essentially unchanged.