Effects of Fish Oil and α-Tocopherol in Immunoglobulin A Nephropathy in the Rat

Abstract

Alpha-tocopherol and fish oil have been reported to modulate the progression of IgA nephropathy in animals and humans. Because fish oil has been reported to exacerbate renal disease in subtotal nephrectomized rats, we investigated the effects of fish oil, with and without alpha-tocopherol, on the course of IgA nephropathy. Experimental IgA nephropathy was induced in male Sprague-Dawley rats, weighing 170-200 g, by oral and i.v. immunization with bovine gamma-globulin for 8 wk. IgA nephropathy was evidenced by hematuria, proteinuria, and IgA deposition in the mesangium. Standard rodent chow, containing 30 IU of alpha-tocopherol/kg of diet, was given to the control and IgA nephropathy rats. Fish oil (20% wt/wt), stripped of alpha-tocopherol preservative, was given to control and a second group of IgA nephropathy rats. Alternatively, corn oil or fish oil was supplemented with alpha-tocopherol at 100 IU/kg of diet and given to the third and fourth groups of IgA nephropathy rats. All animals were killed at 8 wk. Urinary protein excretion, plasma and kidney alpha-tocopherol concentrations, as well as glomerular planar area, and kidney transforming growth factor-beta1 mRNA were analyzed. As determined by reductions in proteinuria, glomerular planar area, and TGF-beta1 mRNA, fish oil with alpha-tocopherol ameliorated the renal injury induced by bovine gamma-globulin, whereas fish oil without alpha-tocopherol did not. Our findings support the importance of alpha-tocopherol, more so than fish oil, in mitigating the injury and promoting repair in experimental IgA nephropathy.

Modulating the Progression in IgA Nephropathy

“…More recently, Branten et al [75] demonstrated no difference between fish oil-treated and untreated controls with IgA nephropathy. It is important to note that the beneficial effects of fish oil may be a consequence of the vitamin E in the fish oil preparation, as shown in experimental IgA nephropathy [76]. These unresolved issues about the use of fish oils demand a careful re-appraisal of its long-term efficacy [77, 78].…”

Growth inhibition of rat mesangial cells by high glucose: effect of vitamin E

“…10 The beneficial effect of fish oil in glomerulosclerosis is likely due to vitamin E supplementation. 11,12 Neoplastic proliferation and arteriosclerotic lesions are inhibited by d-alpha-tocopherol. The proliferation activated by platelet-derived growth factor is particularly sensitive to d-alpha-tocopherol.…”

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

“…Control animals received no BGG throughout the experiment; they were given 6 mM HCl in tap water to drink and 0.2 ml of normal saline intravenously for 3 consecutive days at the end of the experiment. 15 IgA nephropathy model Rats were orally immunized with 0.1% BGG (G7516; Sigma Chemical (St. Louis, MO, USA) in a 6-mM HCl solution as the drinking water 16 for 4 weeks. A second group received BGG in this way for 6 weeks.…”

“…16 Rats were then killed by exsanguination under general anesthesia as described in our previous studies. [13][14][15] All animals were exsanguinated via a catheter placed in the aorta, just below the renal arteries, and blood was saved for α-tocopherol and malondialdehyde (MDA) analysis. Before the right kidney was harvested, the inferior vena cava was incised, and perfusion via the aorta with 0.9% NaCl was performed to remove circulating erythrocytes from the kidney.…”