Determination of urinary glutathione S-transferase and lactate dehydrogenase for differentiation between proximal and distal nephron damage.
Cytosolic glutathione S-transferase (GST) activity is confined to the proximal convoluted and straight tubules. Damage to these parts of the nephron should result in leakage of GST into the urinary space. Lactate dehydrogenase (LDH), in contrast, is more generally distributed along the nephron. Measurement of both enzyme activities could therefore be expected to discriminate between different localizations of nephrotoxicity. To test this hypothesis, we determined both enzyme activities in 24 h urine samples from 10-12 female Sprague-Dawley rats, each treated with single i.p. injections of puromycin aminonucleoside (PAN, 130 mg/kg), Na2 CrO4 10, 20, 30 mg/kg), mercuric chloride (HgCl2, 0.5, 0.75, 1.0 mg/kg), folic acid (125, 350, 375 mg/kg), ethyleneimine (0.5, 2.0, 5.0 microliters/kg). Bovine serum albumin (BSA) was injected by the same method, twice daily on 3 consecutive days (2.5, 7.14 g/kg). The results obtained indicate a characteristic dose- and time-dependent pattern of excreted enzyme activities for each of the tested compounds. In both models with primarily glomerular damage, proximal tubular parts were also affected, as could be demonstrated by increased urinary GST and histopathological changes. Damage, mainly to the S1/S2 segment by 20 or 30 mg Na2 CrO4/kg, resulted in moderate to marked increases in LDH excretion, while GST was only moderately elevated at 30 mg/kg. Extreme increases in GST and LDH output were measured after predominant S3 segment damage after 0.75 and 1.0 mg HgCl2/kg. The distally active compounds, folic acid and ethyleneimine, did not increase GST excretion at lower doses. At the high doses, a small rise in GST excretion indicated some, probably secondary, proximal tubular involvement, which correlated with the histopathological findings in these groups.
Bomhard
E
E
Institute of Industrial Toxicology, Bayer AG, Wuppertal, FRG.
Maruhn
D
D
Vogel
O
O
Mager
H
H
D000818:Animals; D001388:Aziridines / Q000633:toxicity; D002840:Chromates / Q000633:toxicity; D003937:Diagnosis, Differential; D005260:Female; D005492:Folic Acid / Q000633:toxicity; D005982:Glutathione Transferase / Q000652:urine*; D007274:Injections, Intraperitoneal; D007674:Kidney Diseases / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D007681:Kidney Papillary Necrosis / Q000139:chemically induced / Q000201:enzymology; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000652:urine*; D008627:Mercuric Chloride / Q000633:toxicity; D009399:Nephrons / Q000201:enzymology*; D011692:Puromycin Aminonucleoside / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000633:toxicity; D017670:Sodium Compounds
D001388:Aziridines; D002840:Chromates; D017670:Sodium Compounds; D012710:Serum Albumin, Bovine; D008627:Mercuric Chloride; D011692:Puromycin Aminonucleoside; C028982:sodium chromate(VI); D005492:Folic Acid; D007770:L-Lactate Dehydrogenase; D005982:Glutathione Transferase