Influence of alpha-tocopherol over the time course of experimental IgA nephropathy.
The present study investigated the pathogenesis and the time course of kidney injury in experimental IgA nephropathy. In order to determine an appropriate period in the course of experimental IgA nephropathy to study renal injury and repair, we examined proteinuria and IgA deposition in the renal mesangium after 4, 8, and 16 weeks of mucosal challenge by bovine gamma globulins (BGG) provided in the drinking water. The hallmark of IgA deposition in the mesangium was present after 4 weeks and 8 weeks of BGG inoculation, but by 16 weeks, the mesangial IgA deposition had resolved. In addition, we confirmed our previous report on the beneficial effects of alpha-tocopherol in reducing proteinuria in IgA nephropathy at 8 weeks, and extended this observation to investigate the effects of dietary supplementation of alpha-tocopherol at both 4 weeks and 16 weeks. Proteinuria resolved spontaneously at 16 weeks. There is oxidative stress, as suggested by the elevation in plasma and renal malondialdehyde content, and increased fibrogenic cytokine message, as suggested by elevated transforming growth factor beta1 mRNA. These increases were clearly blunted by alpha-tocopherol at both 4 weeks and 8 weeks. Treatment with alpha-tocopherol was associated with a significant reduction in the severity of proteinuria. Thus, our data suggest that the period between 4 and 8 weeks of BGG vaccination could be relevant in designing an appropriate model to study the molecular biology of the pathogenesis of renal injury and the effects of treatment. The 16-week model may be useful in exploring gene expression involved with spontaneous resolution.
Kuemmerle
N B
NB
Department of Pediatrics, Virginia Commonwealth University's Medical College of Virginia Campus, Richmond 23298, USA.
Krieg
R J
RJ
Chan
W
W
Trachtman
H
H
Norkus
E P
EP
Chan
J C
JC
D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D004032:Diet; D005920:Glomerular Mesangium / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000503:physiopathology; D007070:Immunoglobulin A / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009163:Mycobacterium bovis / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D011507:Proteinuria / Q000188:drug therapy / Q000503:physiopathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014810:Vitamin E / Q000627:therapeutic use*
D007070:Immunoglobulin A; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014810:Vitamin E; D008315:Malondialdehyde