Abstract
Fishman and Artom showed that DL-serine was highly toxic to the rat(2). Later papers from their laboratory(3–7), and from that of Wachstein(8–10) implicated the kidney as a prime site for the toxic action of DL-serine. Comparable doses of L-serine were non-toxic (4). With a dose as small as 5 mg D-serine per 100 g (as DL-serine), necrotic plaques were seen in the kidneys of most rats. This necrosis appeared at the corticomedullary junction, in the distal parts of the proximal tubule(9). Other signs of toxicity included weight loss, polyuria, increased urinary sugar, protein, compounds binding with bisulfite, and reducing substances; at higher doses, death occurred. Fishman and Artom(6) noted that the occasional finding of significant amounts of amino acids other than serine in the urine of animals receiving DL-serine may be of interest. These authors pointed out that this hyperaminoaciduria might be due to glycine or cystine derived from serine. Others have indicated that DL-serine injection also results in a large immediate increase in urinary ethanolamine(11), although previous work from Artom's laboratory did not indicate increased ethanolamine excretion until after 2 weeks of continuous DL-serine feeding(6).
In the present study, D-, L-, and DL-serine were injected subcutaneously into rats, and urines were assayed for chromatographically separable ninhydrin-positive compounds. A profound general hyperaminoaciduria was seen following D- or DL-serine injection. The excretion of ethanolamine and several other compounds was only slightly increased. L-serine injection resulted in urine indistinguishable from normal.
Methods. Male Charles River Wistar rats, 11-12 weeks old, weighing 275-320 g were fed Purina Laboratory Pellets ad libitum throughout the experimental period. Two rats were injected subcutaneously in the hind leg with 50 mg L-serine per 100 g body weight, and 2 rats were given the same dose of D-serine. Another 2 rats were given 1001 mg DL-serine per 100 g. All injection solutions
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