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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Clinical and experimental nephrology 3 (1999), S. 250-253 
    ISSN: 1437-7799
    Keywords: Key wordsα-Tocopherol ; 5/6 Nephrectomy ; Remnant ; Phospholipase A2 mRNA ; Activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Glomerulosclerosis is a characteristic feature in the subtotal (5/6) nephrectomy, remnant kidney model in the rat. It is postulated that oxidative stress from this renal mass reduction may induce the glomerular and tubular injury leading eventually to glomerulosclerosis. In support of this line of reasoning, an antioxidant, α-tocopherol, has been recently demonstrated to prevent such injury. Because group IIA phospholipase A2 is upregulated in a variety of injuries including ischemic proximal tubular necrosis, we examined whether up-regulation of phospholipase A2 is associated with the initiation of injury leading to the glomerulosclerosis and whether α-tocopherol can modulate such activity. Methods. We set out to examine whether secretory group IIA phospholipase A2 (sPLA2) mRNA levels (Northern analysis) are increased in the remnant kidney and whether α-tocopherol has the capacity to modulate steady-state sPLA2 transcription levels. Results. Our data indicate that there is overproduction of sPLA2 message, and that α-tocopherol reduces the steady-state levels of sPLA2 mRNA in the remnant kidney. Total PLA2 enzymatic activity from homogenate of the remnant kidney strongly paralleled the Northern data. Conclusion. The results support a possible role of sPLA2 in the renal injury accompanying sudden reduction of renal mass and provide an additional rationale for the potential utility of α-tocopherol in modulating such injury in progressive renal disease.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Clinical and experimental nephrology 4 (2000), S. 187-192 
    ISSN: 1437-7799
    Keywords: Key words IgA nephropathy ; Rats ; Oxidative stress ; Malondialdehyde ; TGFβ1 mRNA ; α-Tocopherol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. We have previously shown that α-tocopherol prevents oxidative stress in experimental IgA nephropathy (IgAN) when administered before or concurrent with the induction of IgAN. We now seek to determine whether α-tocopherol can ameliorate the disease after IgAN is established. Methods. Using the classic IgAN model, 25 male Lewis rats were sorted into five groups of five animals each: 4-week control, 4-week bovine gamma globulin (BGG) treatment, 6-week control, 6-week BGG treatment, and 6-week BGG treatment with α-tocopherol administration started after 4 weeks. Serum α-tocopherol concentrations, kidney and plasma malondialdehyde concentrations, and kidney transforming growth factor beta-1 (TGFβ1) mRNA were analyzed. Results.α-Tocopherol modulated IgAN after the disease was established in the 4-week BGG model, as indicated by the reduction in tissue oxidative stress, dampening of fibrogenic cytokine (TGFβ1), and abatement of proteinuria in α-tocopherol-treated animals compared with untreated rats. Conclusions. These results substantiate the anti-oxidant role of α-tocopherol in diminishing the indices associated with progression of experimental IgAN. The ability of α-tocopherol to reduce the progression of injury after establishment of the disease reflects the clinical situation, and thus holds promise for human therapy.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-198X
    Keywords: Key words Gene therapy ; Delivery to kidney ; Naked DNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Effective gene therapy requires efficient delivery and expression of the necessary genetic information to the target tissue. We demonstrate here that plasmid DNA, injected as naked, uncomplexed DNA into the cortical region of rat kidney, or intravenously, is localized and expressed in the kidney. The plasmid pRSVZ contained the Rous sarcoma virus promoter and a reporter gene, the β-galactosidase gene, derived from bacteria. The β-galactosidase gene hydrolyzes the artificial substrate X-gal to produce an intense blue color in cells that have taken up and expressed the plasmid genes. We have used X-gal staining and Western blotting to study plasmid gene expression 1, 4, and 8 days and 6 months after intrarenal injection of 50 µg of plasmid DNA and at 1 and 4 days after intravenous injection. Expression was apparent in the kidneys and several other tissues 24 h after injection and persisted for at least 8 days; expressed proteins could still be detected in the injected kidney 6 months later. These observations were corroborated by use of a plasmid, pEGFP-Puro, harboring the cytomegalovirus promoter in conjunction with a different reporter gene, the green fluorescent protein (GFP). Histological localization and Western blotting analysis of GFP expression after intrarenal injection of pEGFP-Puro paralleled results obtained with the plasmid pRSVZ. Our findings support the suggestion that intrarenal or intravenous injection of naked plasmid DNA may be an effective means of delivering therapeutic genes to the kidney and several other tissues.
    Type of Medium: Electronic Resource
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