ISSN:
1437-7799
Keywords:
Key words Low density lipoprotein
;
Apoptosis
;
Malondialdehyde
;
TGFβ1
;
Unilateral ureteral obstruction
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background. To test the hypothesis that oxidized low density lipoprotein (oLDL) is involved in the renal injury of obstructive nephropathy, male Sprague-Dawley rats weighing 125–150 g were used. Methods. Three days after arrival, the rats were randomly assigned to undergo: (1) sham operation, (2) left unilateral ureteral obstruction (UUO), or (3) reversal of the unilateral ureteral obstruction (R-UUO). Seven days after the reversal operation or 10 days after the sham or UUO procedure, all animals were killed by exsanguination under anesthesia, with blood taken from the abdominal aorta. LDL was prepared by gradient ultracentrifugation and used immedi-ately after isolation. Rat mesangial cells were utilized with an LDL concentration of 100 μg/ml/protein in the media. After 72 h, cell survival was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) method. Cell survival was determined by comparing the optical density between the control wells and the experimental wells. In order to investigate the mechanisms of injury and repair of obstructive nephropathy, data for kidney apoptosis, malondialdehyde (MDA), and transforming growth factor β1 (TGFβ1) mRNA were obtained in the sham-operated, UUO, and R-UUO groups. Results. Our results showed that LDL malondialdehyde during UUO was increased 87% over baseline values (P 〈 0.005). With R-UUO, the oxidized LDL dropped 23% from the peak values during UUO (P 〈 0.005), but was still different from that of the baseline values (P 〈 0.025). Rat mesangial cell survival, after 72 h exposure to oLDL, inversely correlated to oLDL cytotoxicity and showed a 14% drop during UUO compared with sham-operated animals (P 〈 0.01). Cell survival increased 11% after R-UUO (P 〈 0.02) and was not different from control values (P = NS). The apoptotic counts by the TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling) technique showed significant increases during UUO and a noticeable reduction after R-UUO. Conclusion. Our data support the proposition that UUO stimulates oxidation of LDL. The cytotoxicity of oLDL plays a significant role in the injury of UUO. A decrease in cytotoxicity was associated with the repair in R-UUO. Our observations that apoptosis follows this same pattern, point to the importance of apoptosis in the injury and repair of obstructive nephropathy. Future studies to interrupt these processes of injury may lead to novel treatment modalities in reversing the injury and hastening the repair of obstructive nephropathy.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s101570050044
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