Determination of urinary glutathione S-transferase and lactate dehydrogenase for differentiation between proximal and distal nephron damage

Abstract

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.

The low calorie natural sweetener stevioside: Nephrotoxicity and its relationship to urinary enzyme excretion in the rat

“…GSH-S-TF is abundant in the cytosol of the proximal tubule cells of the rat (Bomhard et al, 1990). Urinary GSH-S-TF excretion revealed a marked dose and timedependence after mercuric chloride and potassium dichromate administration (Feinfeld et al, 1977;Bomhard et al, 1990). However, our finding showed that the activity of GSH-S-TF in the urine of steviosidetreated rats was slightly lower than in control rats.…”

“…The results obtained suggest that stevioside at the dose, time intervals and with the route of administration used may not have been sufficient to effect lysosomal damage in rat renal proximal convoluted tubule cells. GSH-S-TF is abundant in the cytosol of the proximal tubule cells of the rat (Bomhard et al, 1990). Urinary GSH-S-TF excretion revealed a marked dose and timedependence after mercuric chloride and potassium dichromate administration (Feinfeld et al, 1977;Bomhard et al, 1990).…”

Localization of annexin V in rat normal kidney and experimental glomerulonephritis

“…LDH is distributed in all sites of the nephron [2,22]. Urinary LDH showed a high value during relapse of nephrotic syndrome, which was considered to be the result of renal tissue damage [20].…”

Renal Biomarkers: Review

“…Nefronun tüm bölüm-lerinde sitozolde yerleşmiş ve piruvat oksidasyonu reaksiyonunda görev alan ve renal patolojilerin çoğunda idrarda artmış olarak bulunan bir enzimdir (24,25) .…”