Urinary Ligandin and Glutathione-S-Transferase in Gentamicin-Induced Nephrotoxicity in the Rat

1981 ◽  
Vol 61 (1) ◽  
pp. 123-125 ◽  
Author(s):  
D. A. Feinfeld ◽  
G. M. Fleischner ◽  
I. M. Arias

1. Eight rats developed detectable glutathione-S-transferase activity in their urine after three daily injections of toxic doses of gentamicin. 2. Seven of the eight rats had immunodetectable ligandin in their urine at this time. 3. The level of enzyme activity correlated well with the degree of elevation of serum creatinine. 4. This confirms ligandinuria and urinary glutathione-S-transferase as markers of acute renal proximal tubular injury.

2010 ◽  
Vol 38 (6) ◽  
pp. 943-956 ◽  
Author(s):  
Jean-Charles Gautier ◽  
Björn Riefke ◽  
Jakob Walter ◽  
Petra Kurth ◽  
Lou Mylecraine ◽  
...  

Cisplatin is an anticancer agent that induces renal proximal tubule lesions in many species. Studies were conducted in Sprague-Dawley and Han-Wistar rats to evaluate the utility of novel preclinical biomarkers of nephrotoxicity for renal lesions caused by this compound. Groups of 10 males of each strain were given a single intraperitoneal injection of 0.3, 1, or 3 mg/kg cisplatin and were sacrificed on days 2, 3, and 5. The novel biomarkers α-glutathione-S-transferase (α-GST) (for proximal tubular injury), μ-glutathione-S-transferase (μ-GST) (for distal tubular injury), clusterin (for general kidney injury), and renal papillary antigen-1 (RPA-1) (for collecting duct injury) were measured in urine by enzyme immunoassay. Histologically, degeneration and necrosis of the S3 segment of the renal proximal tubule were observed on day 2 (Han-Wistar) and days 3 and 5 (both strains) at 1 and 3 mg/kg. Results showed that in both strains of rats, urinary α-GST and clusterin can be detected in urine soon after injury, are more sensitive than BUN and serum creatinine, and therefore are usable as noninvasive biomarkers of proximal tubule injury. Changes in both μ-GST or RPA-1 were considered to represent secondary minor effects of proximal tubular injury on distal segments of the nephron.


1995 ◽  
Vol 92 (17) ◽  
pp. 7662-7666 ◽  
Author(s):  
C. L. Edelstein ◽  
E. D. Wieder ◽  
M. M. Yaqoob ◽  
P. E. Gengaro ◽  
T. J. Burke ◽  
...  

2014 ◽  
Vol 50 (No. 3) ◽  
pp. 135-144 ◽  
Author(s):  
F. Piri ◽  
A. Sahragard ◽  
M. Ghadamyari

The susceptibility of G. pyloalis larvae to spinosad was studied using the leaf dip method. Treatment with doses of spinosad sublethal concentrations (LC<sub>10</sub>, LC<sub>20</sub>, LC<sub>30</sub>, LC<sub>40</sub> of 0.026, 0.045, 0.065, 0.090 ppm, respectively) was applied. A significant difference in the effects was observed between the sublethal concentrations (LC<sub>10</sub>, LC<sub>20</sub>, LC<sub>30</sub>, and LC<sub>40</sub>) and the control in the content of carbohydrate and glycogen, and between the control vs. LC<sub>30</sub> and LC<sub>40</sub> in the content of protein. A significant decrease in glutathione S-transferase activity with the increase of spinosad concentration, no significant differences in the activities of &alpha;- and &beta;-esterases, and a significant increase in the enzyme activity of phenoloxidase were observed. Effects of LC<sub>10</sub> and LC<sub>30</sub> spinosad concentrations on some biological parameters showed that percentage of larval pupation and female fecundity significantly decreased in the concentration of LC<sub>30</sub>.


1980 ◽  
Vol 188 (2) ◽  
pp. 475-479 ◽  
Author(s):  
R C Strange ◽  
J D Johnston ◽  
D R Coghill ◽  
R Hume

Glutathione S-transferase activity was measured in partially purified haemolysates of erythrocytes from human foetuses and adults. Enzyme activity was present in erythrocytes obtained between 12 and 40 weeks of gestation. The catalytic properties of the enzyme from foetal cells were similar to those of the enzyme from adult erythrocytes, indicating that probably only one form of the erythrocytes enzyme exists throughout foetal and adult life.


1979 ◽  
Vol 181 (3) ◽  
pp. 699-708 ◽  
Author(s):  
J D Hayes ◽  
R C Strange ◽  
I W Percy-Robb

1. Two lithocholic acid-binding proteins in rat liver cytosol, previously shown to have glutathione S-transferase activity, were resolved by CM-Sephadex chromatography. 2. Phenobarbitone administration resulted in induction of both binding proteins. 3. The two proteins had distinct subunit compositions indicating that they are dimers with mol.wts. 44 000 and 47 000. 4. The two lithocholic acid-binding proteins were identified by comparing their elution volumes from CM-Sephadex with those of purified ligandin and glutathione S-transferase B prepared by published procedures. Ligandin and glutathione S-transferase B were eluted separately, as single peaks of enzyme activity, at volumes equivalent to the two lithocholic acid-binding proteins. 5. Peptide ‘mapping’ revealed structural differences between the two proteins.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Wen-Ling Kang ◽  
Gao-Si Xu

Abstract Atrasentan is a promising therapy for treating diabetic nephropathy (DN). Here we evaluated whether atrasentan down-regulated the miR-199b-5p expression, thereby increasing klotho and preventing renal tubular injury in DN. One-hundred patients with type 2 diabetes mellitus (T2DM) and 40 healthy subjects were included. A DN mice model was established by an injection of streptozotocin (STZ). Human renal proximal tubular epithelial HK-2 cells were exposed to high glucose (20 mmol/L). Treated the mice and HK-2 cells with atrasentan and we then investigated whether and how miR-199b-5p and Klotho were involved in preventing renal tubular injury in DN. In patients, the serum miR-199b-5p level increased and the klotho concentration decreased in accordance with elevated albuminuria. Atrasentan down-regulated miR-199b-5p and up-regulated klotho of the DN mice and HK-2 cells exposed to high glucose. High glucose promoted the binding of histone H3 to the miR-199b-5p promoter and atrasentan canceled this effect. MiR-199b-5p targeted the 3′ UTR of klotho. Overexpression of miR-199b-5p canceled the effects of atrasentan on klotho expression and apoptosis of renal tubular cells in both in vivo and in vitro. The increased serum klotho, mediated by miR-199b-5p, is a possible mechanism by which atrasentan prevents renal tubular injury in DN.


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