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Alpha-tocopherol modulates lipoprotein cytotoxicity in obstructive nephropathy.
P Saborio1, R J Krieg, N B Kuemmerle
1Department of Pediatrics, Virginia Commonwealth University's Medical College of Virginia Campus, Richmond, USA.
Pediatric Nephrology (Berlin, Germany)
|August 24, 2000
Summary
Oxidized low-density lipoprotein (oLDL) contributes to kidney injury in unilateral ureteral obstruction (UUO). Alpha-tocopherol treatment reduced oLDL oxidation and its cytotoxic effects, suggesting a protective role in UUO-induced renal damage.
Area of Science:
- Nephrology
- Oxidative Stress Research
- Biochemistry
Background:
- Unilateral ureteral obstruction (UUO) leads to kidney injury, with oxidative stress playing a key role.
- The specific contribution of oxidized low-density lipoprotein (oLDL) to UUO-induced renal pathogenesis remains unclear.
Purpose of the Study:
- To investigate the role of oLDL in kidney injury associated with UUO.
- To determine if alpha-tocopherol can mitigate oLDL-induced cytotoxicity and promote renal repair in a UUO model.
Main Methods:
- Male Sprague-Dawley rats underwent sham surgery or UUO, with some UUO rats receiving alpha-tocopherol supplementation.
- Oxidative stress was assessed by measuring malondialdehyde (MDA) levels in plasma and kidneys.
- Cytotoxicity of isolated LDL was evaluated using rat mesangial cells in vitro.
- Transforming growth factor beta1 (TGF-β1) mRNA expression was analyzed.
Main Results:
- UUO significantly increased plasma and kidney MDA levels, indicating elevated oxidative stress.
- LDL isolated from UUO rats exhibited cytotoxicity towards mesangial cells.
- Alpha-tocopherol treatment significantly reduced MDA levels and oLDL-induced cytotoxicity.
- Plasma cholesterol, kidney MDA, and TGF-β1 mRNA expression were elevated in UUO rats and partially reduced by alpha-tocopherol.
Conclusions:
- Oxidative modification of LDL is implicated in the renal injury observed in UUO.
- Alpha-tocopherol demonstrates a capacity to modulate LDL oxidation and its detrimental effects on kidney cells, offering potential therapeutic benefits in UUO.