alpha-Tocopherol reduces proteinuria, oxidative stress, and expression of transforming growth factor beta 1 in IgA nephropathy in the rat.
Oxidative stress and the fibrogenic cytokine transforming growth factor beta 1 (TGF beta 1) have been implicated in the pathogenesis and progression of IgA nephropathy. In the present study, we used alpha-tocopherol as a dietary supplement to test the hypothesis that the proteinuria, oxidative stress, and TGF beta mRNA can be more effectively lowered with higher doses of alpha-tocopherol. Hematuria, proteinuria, and mesangial IgA deposition are parameters which characterize IgA nephropathy. IgA nephropathy was induced by bovine gamma globulin oral immunization in rats during an 8-week course, and all hallmarks of IgA nephropathy were produced in this 8-week animal model. The elevation in renal malondialdehyde content and TGF beta 1 mRNA, as well as the severity of proteinuria, was blunted by alpha-tocopherol. Our data suggested that conventional dosage of alpha-tocopherol at 100 IU/kg chow lowered kidney TGF beta 1 to control values and increasing the dose by 2 1/2-fold or even 5-fold resulted in no further reduction in TGF beta 1 mRNA. Significant reduction of proteinuria was achieved better with a dose of 250 IU/kg chow of alpha-tocopherol supplementation than with the 100 IU/kg chow. We conclude that alpha-tocopherol at this dose is efficacious in controlling proteinuria, downregulating TGF beta 1, and reducing oxidative stress in experimental IgA nephropathy. Doubling this dose achieved no further benefits.
Chan
W
W
Department of Pediatrics, Virginia Commonwealth University's Medical College of Virginia, Richmond 23298, USA.
Krieg
R J
RJ
Norkus
E P
EP
Chan
J C
JC
D000818:Animals; D015152:Blotting, Northern; D004032:Diet; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D011507:Proteinuria / Q000150:complications / Q000188:drug therapy*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D014810:Vitamin E / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D015430:Weight Gain
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014810:Vitamin E; D008315:Malondialdehyde