Indices of progression of IgA nephropathy are modulated by α-tocopherol in rats

Ward, K. P.; Kuemmerle, Nancy B.; Krieg, Richard J.; Saborío, Pablo; Norkus, Edward P.; Chan, James C.M.

doi:10.1007/s101570070020

Cited by 3 publications

(2 citation statements)

References 18 publications

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“…Experimental IgAN was induced in rats by oral immunization with 0.1% bovine gamma-globulin (BGG) in 6 mM HCl for 8 weeks and followed by intravenous injection of 1 mg BGG daily for 3 successive days as described previously (Gesualdo et al, 1992;Kuemmerle et al, 1999;Ward et al, 2000). Rats from the control and control + S3F groups were maintained with normal drinking water containing 6 mM HCl.…”

Section: Animals and Treatmentsmentioning

confidence: 99%

The Study of Chinese Medicinal Herbal Formula Shen San Fang in the Treatment of Experimental IgA Nephropathy

et al. 2005

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IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, yet there is no effective or specific therapy. Shen San Fang (S3F) is a traditional Chinese herbal medicinal formula that has been used in China for many years to treat patients with hematuria. The aim of this study is to test the therapeutic value of S3F in an experimental model of IgAN. IgAN was induced in Lewis rats by continuous oral immunization with bovine gamma-globulin (BGG) in the drinking water for 8 weeks, followed by intravenous injection of 1 mg BGG daily for 3 successive days. The rats were randomly divided into four groups (five rats/group): control, control receiving S3F, induction of IgAN, and IgAN receiving S3E S3F decoction was fed to rats beginning week 4 from the first day of oral sensitization with BGG. The S3F treatment was continued until the rats were sacrificed or for a 4-week period. Hematuria, renal immunohistochemistry for IgA and transforming growth factor-beta 1 (TGF-beta1), renal histopathology, and renal content of TGF-beta1 were measured. Rats developing IgAN had marked hematuria, profound mesangial proliferation and mesangial expansion, intense and diffuse glomerular IgA deposition, increased glomerular TGF-beta1 expression, and raised renal TGF-beta1 levels. S3F treatment resulted in a significant reduction of hematuria, decreased mesangial IgA deposition, weaker immunostaining of TGF-beta1 in glomerulus, and a lower renal TGF-beta1 concentration. Our animal data suggests a therapeutic value for the Chinese medicinal formula S3F in experimental IgAN. This beneficial effect was due to reduced glomerular IgA deposition and TGF-beta1 expression. Our preliminary findings hold promise for future human therapy.

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Section: Animals and Treatmentsmentioning

confidence: 99%

The Study of Chinese Medicinal Herbal Formula Shen San Fang in the Treatment of Experimental IgA Nephropathy

et al. 2005

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“…Recently, Ward and coworkers [61]demonstrated the anti-oxidant role of α-tocopherol in diminishing the indices associated with progression of experimental IgAN. Treatment with α-tocopherol was associated with reduction in tissue oxidative stress, dampening of TGF-β, and abatement of proteinuria in murine model of IgAN.…”

Section: Reducing the Noxious Glomerular Injury Due To Infiltrating Nmentioning

confidence: 99%

Future Directions in the Treatment of IgA Nephropathy

Lai

2002

Nephron

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IgA nephropathy (IgAN) is the most common primary glomerulonephritis yet its etiology remains uncertain. Recent data suggest a structural aberration of the IgA molecule in IgAN that may exert pathophysiologic effects on target cells, reduce clearance of IgA-immune complexes (IC), or favor mesangial IC trapping. Mesangial reactivity to immune complexes triggers off the release of cytokines and the alteration of prostaglandin and thromboxane A₂ production promoting mesangial cell proliferation. Angiotensin II-induced mesangial cells contraction with efferent arteriolar vasodilatation initiates glomerular injury and eventually lead to glomerulosclerosis following increased local production of transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF). This paper highlights the potential therapeutic strategies in the future. These strategies include: (i) decreasing the synthesis of IgA-IC; (ii) limiting the mesangial uptake of IgA-IC; (iii) antagonizing the effect of PDGF and TGF-β to reduce mesangial proliferation and glomerulosclerosis; and (iv) reducing the noxious glomerular injury due to infiltrating neutrophils. The effective treatment of IgAN requires a better clarification of the pathogenesis of the nephropathy. Future therapeutic attempts to slow down the renal deterioration should target at prevention of mesangial IgA deposition and the amelioration of inflammatory injury induced by infiltrating neutrophils and the released cytokines.

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Vitamin E in renal therapeutic regimens

Thabet

Chan

2006

Pediatr Nephrol

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Administration of vitamin E in children with immunoglobulin A (IgA) nephropathy, focal segmental glomerulosclerosis (FSGS) and type I diabetes demonstrated potential towards ameliorating progression. Oral vitamin E therapy reduced endothelial dysfunction, lipid peroxidation and oxidative stress in patients with chronic kidney failure (CKF). Moreover, the use of vitamin E-bonded hemodialyzers reduced atherosclerotic changes, erythropoietin dosage and muscular cramps in patients on hemodialysis (HD). However, several controlled clinical trials failed to document beneficial effects on the study subjects' cardiovascular and renal outcomes. A recent report of increased all-cause mortality in adult patients receiving high dose vitamin E therapy has caused considerable concern and debate. These issues regarding the efficacy and safety of vitamin E in renal therapeutic regimens will be reviewed in this article.

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Indices of progression of IgA nephropathy are modulated by α-tocopherol in rats

Cited by 3 publications

References 18 publications

The Study of Chinese Medicinal Herbal Formula Shen San Fang in the Treatment of Experimental IgA Nephropathy

The Study of Chinese Medicinal Herbal Formula Shen San Fang in the Treatment of Experimental IgA Nephropathy

Future Directions in the Treatment of IgA Nephropathy

Vitamin E in renal therapeutic regimens

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