The levels of serum orosomucoid, haptoglobin, and seromucoid were evaluated as possible quantitative criteria for the estimation of drug efficiency in adjuvant arthritis and nephrotoxic serum nephritis. In adjuvant arthritis, haptoglobin, seromucoid, and chiefly orosomucoid serum levels were generally very sensitive to anti-inflammatory agents such as phenylbutazone and pyridinol carbamate, and to immunosuppressive agents such as L-asparaginase. There was a significant correlation between the serum levels of these glycoproteins and the arthritis scores. In nephrotoxic serum nephritis, seromucoid levels were correlated with the proteinuria of the autologous phase and were found to be a good complementary criterion for the analysis of the efficiency of pyridinol carbamate, colchicine, iysine acetylsalicylate, and L-asparaginase.
During tubulonephritis, we observed one sharp excretion peak of all 5 enzymes on day 1. During regeneration of tubular epithelium, lysosomal enzymes decreased below normal level. Isoenzyme analysis gave most interesting results for aspartate aminotransferase: on the first days, while total activity was increased in urine and serum, 2 fractions were found in serum and 3 in urine while only one (cytoplasmic) in normal rat serum; the mitochondria! fraction appeared indicative of tissue necrosis; the third fraction only found in urine migrated towards the anode faster than albumin at pH 8.6 and was never detected in serum. Serum lactic dehydrogenase activity was increased and its isoenzyme pattern was reversed on day 1 when isoenzyme 1 characteristic of kidney cortex predominated. Lactic dehydrogenase isoenzymes 1 and 2 predominated in urine. Urinary enzyme activities after tubular necrosis seem to originate mainly in the cortical tubules. During glomerulonephritis we observed increased urinary activities of the 5 enzymes which culminated during the 2 periods of highest proteinuria: 1) the heterologous phase limited to the first days 2) the autologous phase maximum at the second week. A significant diminution was noted in serum, for alkaline phosphatase during the autologous phase. The only isoenzyme of aspartate aminotransf erase detected in urine at the periods of high enzymuria appeared identical to the isoenzyme present in serum. Urinary enzyme activities during glomerulonephritis appear to originate mainly in the plasma or in the glomeruli.
Haptoglobin and orosomucoid were detected and measured in concentrated normal rat urine by radial immunodiffusion. Normal haptoglobin clearance was 33 nl/min (190 nl/ min/kg) and normal orosomucoid clearance 146 nl/min (840 nl/ min/kg). During nephrotoxic serum glomerulonephritis both glycoproteins increased considerably in urine in two phases; in serum, after an early peak, haptoglobin returned to the normal level and orosomucoid fell below the normal value. During mercuric chloride tubulonephritis, an early sharp peak of both glycoproteins was observed chiefly in urine but also in serum.
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