The excretion of lactate dehydrogenase in human urine after ingestion of aspirin

Abstract

1. Cells present in normal human urine contain 5-10% of the total lactate dehydrogenase excreted. The enzyme released from these cells by ultrasonication contained a distribution of isoenzymes similar to that found in the bulk of the urine and it is suggested that these cells are the main source of urinary lactate dehydrogenase. 2. Cells were thoroughly washed before examination so it is unlikely that the enzyme found in urinary sediment was simply adsorbed. In addition, full recoveries of added lactate dehydrogenase isoenzymes LDH(1) and LDH(5) showed that adsorption did not occur. 3. Most of the cells in normal urine are of the non-squamous epithelial type and their excretion is greatly increased after the ingestion by the subject of 3g. of aspirin. The possible origin of these non-squamous cells from the kidney is discussed. 4. Starch-block electrophoresis and relative activity measurements of lactate dehydrogenase excreted after the subject had taken aspirin show that the enzymes present in urine and cells are very similar, confirming the conclusion reached above (point 1). They have slightly more M subunits than the normal, shown particularly as an increase in isoenzyme LDH(2). The isoenzyme pattern is like that of the kidney medulla and the possible reasons for this are discussed in terms of the concentration of salicylic acid in various parts of the kidney. 5. The results confirm the previous suggestion that the kidney is the main source of urinary lactate dehydrogenase.

Assessment of nephrotoxicity.

“…These enzymes include aminotransferases, isocitric dehydrogenase, lactic dehydrogenase, alkaline phosphatase, f-glucuronidase, leucine, alanine and glutamyl aminopeptidases, glucosidases and Nacetyl-,(-glucosaminidase (NAG) (Balazs et al, 1963;Ono et al, 1968;Raab & Hohenegger, 1968;Prescott & Ansari, 1969;Leathwood & Plummer, 1969;Raab, 1972;Wright & Plummer, 1974;Wellwood et al, 1975Wellwood et al, , 1976Stroo & Hook, 1977;Mondorf et al, 1978;Procter & Kunin, 1978;Merle et al, 1980;Jones et al, 1980: and others). Depending on the severity of the injury there is an initial delay of 12-48 h after administration of the nephrotoxic agent before the rise in urine enzyme activity.…”

“…Depending on the severity of the injury there is an initial delay of 12-48 h after administration of the nephrotoxic agent before the rise in urine enzyme activity. Enzymuria increases in parallel with a marked increase in renal tubular cell excretion and at this time there is histological evidence of proximal tubular necrosis (Balazs etal., 1963;Leathwood & Plummer, 1969;Prescott & Ansari, 1969). Raab (1972) described two periods of maximal enzyme activity in rats given aspirin-once during the first 24 h and again on the second and third days corresponding to the appearance of large numbers of renal tubular cells in the urine.…”

“…Mondorf et al (1978) found decreasing cyclic elevation of urinary alanine aminopeptidase with peak activity occurring every 20-26 h in healthy volunteers after the last of three daily doses of amikacin, suggesting damage to regenerating cells at the same stage of maturation. Enzymes appearing in the urine following administration of nephrotoxins are thought to be derived largely from proximal tubular cells, but following the administration of aspirin the lactic dehydrogenase isoenzyme pattern suggests an origin from the lower nephron also (Leathwood & Plummer, 1969).…”

“…Strikingly increased urinary excretion of renal tubular cells has been reported by numerous investigators in experimental animals and man following administration of various nephrotoxins (Balazs et al, 1963;Scott, Denman & Dorling, 1963;Prescott, 1965;Davies & Kennedy, 1967;Gent etal., 1968;Brown & Hardy, 1968;Leathwood & Plummer, 1969;Raab, 1969;Prescott & Ansari, 1969;Hardy, 1970). Most cells are believed to come from the proximal tubules, and histochemical staining may be useful to identify the sites of origin (Scott et al, 1963;Hardy, 1970).…”

Biochemical Changes in the Rat during Experimentally Induced Acute Ochratoxicosis

“…The rats were housed individually in metabolism cages (Associated Crates Ltd., Stockport, UK) with food and water ad libitum, and the urine samples collected were prepared for measurement as previously described [20,21]. The data obtained from the urine samples from a group of 10 rats on 3 consecutive days before the administra tion of ochratoxin A served as controls.…”