Abstract
α-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 α-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 γ-globulin for 8 wk. IgA nephropathy was evidenced by hematuria, proteinuria, and IgA deposition in the mesangium. Standard rodent chow, containing 30 IU of α-tocopherol/kg of diet, was given to the control and IgA nephropathy rats. Fish oil (20% wt/wt), stripped ofα-tocopherol preservative, was given to control and a second group of IgA nephropathy rats. Alternatively, corn oil or fish oil was supplemented with α-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 α-tocopherol concentrations, as well as glomerular planar area, and kidney transforming growth factor-β1 mRNA were analyzed. As determined by reductions in proteinuria, glomerular planar area, and TGF-β1 mRNA, fish oil with α-tocopherol ameliorated the renal injury induced by bovineγ-globulin, whereas fish oil without α-tocopherol did not. Our findings support the importance of α-tocopherol, more so than fish oil, in mitigating the injury and promoting repair in experimental IgA nephropathy.
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Abbreviations
- BGG:
-
bovine γ-globulin
- TGF-β1:
-
transforming growth factorβ1
- TBHQ:
-
tertiary butylhydroquinone
References
Berger J, Hinglais N 1968 Les depots intracapillaires d'IgA-IgG. J Urol 73: 694–695.
Donadio JV, Grande JP 1989 Immunoglobulin A nephropathy: a clinical perspective. J Am Soc Nephrol 8: 1324–1332.
Galla JH 1995 Perspectives in clinical nephrology. IgA nephropathy. Kidney Int 47: 377–387.
Julian BA, Waldo B, Rifai A, Mestecky J 1988 IgA nephropathy, the most common glomerulonephritis worldwide: a neglected disease in the United States?. Am J Med 84: 129–132.
Cattran DC, Greenwood C, Ritchie S 1994 Long-term benefits of angiotensin-converting enzyme inhibitor therapy in patients with severe immunoglobulin A nephropathy: a comparison to patients receiving treatment with other antihypertensive agents and to patients receiving no therapy. Am J Kidney Dis 23: 247–254.
Scheinman JI, Trachtman H, Lin C-Y, Langman CB, Chan JCM 1997 IgA nephropathy: to treat or not to treat?. Nephron 75: 251–258.
Donadio JV, Bergstralh EJ, Offord KP, Spencer DC, Holley KE 1994 A controlled trial of fish oil in IgA nephropathy. N Engl J Med 331: 1194–1199.
Pei Y, Scholey J, Thai K, Suzuki M, Cattran D 1997 Association of angiotensinogen gene T235 variant with progression of immunoglobulin A nephropathy in Caucasian patients. J Clin Invest 100: 814–820.
Chen A, Chen WP, Sheu LF, Lin CY 1994 Pathogenesis of IgA nephropathy: in vitro activation of human mesangial cells by IgA immune complexes. J Pathol 173: 119–126.
Kashem A, Masayuki E, Nomoto Y, Sakai H, Nakazawa H 1994 FcαR expression on polymorphonuclear leukocyte and superoxide generation in IgA nephropathy. Kidney Int 45: 868–875.
Trachtman H, Chan JCM, Chan W, Valderrama E, Brandt R, Wakely P, Futterweit S, Maesaka J, Ma C 1996 Vitamin E ameliorates renal injury in an experimental model of immunoglobulin A nephropathy. Pediatr Res 40: 620–626.
Emancipator SN, Gallo GR, Lamm ME 1983 Experimental IgA nephropathy induced by oral immunization. J Exp Med 157: 572–582.
Yi ZW, Rodriguez GE, Krieg RJ Jr, Tokieda K, Chan, JCM 1996 Rat macrophages in experimental IgA nephropathy. Biochem Mol Med 57: 52–155.
Chan W, Valerie KC, Chan JCM 1993 Expression of insulin-like growth factor-1 in uremic rats: growth hormone resistance and nutritional intake. Kidney Int 43: 790–795.
Sowell AL, Huff DL, Yeager PR, Caudill SP, Gunter EW 1994 Retinol, α-tocopherol, lutein/zeaxanthin, β-cyptoxanthin, lycopene, α-carotene, trans β-carotene, and four retinyl esters in serum determined simultaneously by reversed-phase HPLC with multiwavelength detection. Clin Chem 40: 411–416.
Schmitz HH, Poor CL, Wellman RB, Erdman JW 1991 Concentrations of selected carotenoids and vitamins in human liver, kidney and lung tissue. J Nutr 121: 1613–1621.
Bennett WM, Walker RG, Kincaid-Smith P 1989 Treatment of IgA nephropathy with eicosapentaenoic acid: a two-year prospective trial. Clin Nephrol 31: 128–131.
Cheng IKP, Chan PCK, Chan KK 1990 The effect of fish-oil dietary supplement on the progression of mesangial IgA glomerulonephritis. Nephrol Dial Transplant 5: 241–246.
Pettersson EE, Rekola S, Berglund L, Sundqvist KG, Angelin B, Diczfalusky U, Bjorkhem I, Bergstrom J 1994 Treatment of IgA nephropathy with ω-3-polyunsaturated fatty acids: a prospective, double-blind, randomized study. Clin Nephrol 41: 183–190.
Scharschmidt LA, Gibbons NB, McGarry L, Berger P, Axelrod M, Janis R, Ko YH 1987 Effects of dietary fish oil on renal insufficiency in rats with subtotal nephrectomy. Kidney Int 32: 700–709.
Tateno S, Kobayashi Y, Robinson DR 1997 Dietary fish oil supplementation exacerbates serum sickness nephritis in mice. Nephron 77: 86–92.
Clark WF, Parbtani A, Philbrick DJ, Holub BJ, Huff MW 1991 Chronic effects of ω-3 fatty acids (fish oil) in a rat 5:6 renal ablation model. J Am Soc Nephrol 1: 1343–1353.
Bilo HJG, van der Heide JJH, Gans ROB, Donker AJM 1991 Omega-3 polyunsaturated fatty acids in chronic renal insufficiency. Nephron 57: 385–393.
Purkerson ML, Joist JH, Valdes A, Yates J, Morrison A, Klahr S 1985 Inhibition of thromboxane synthesis ameliorates the progressive kidney disease of rats with subtotal ablation. Proc Natl Acad Sci USA 82: 193–197.
Diaz MN, Frei B, Vita JA, Keaney JF 1997 Antioxidants and atherosclerotic heart disease. N Engl J Med 337: 408–416.
McGrath LT, Brennan GM, Donnelly JP, Johnston GD, Hayes JR, McVeigh GE 1996 Effect of dietary fish oil supplementation on peroxidation of serum lipids in patients with non-insulin dependent diabetes mellitis. Atherosclerosis 121: 275–283.
Cho SH, Im JG, Choi YS, Son YS, Chung MH 1995 Lipid peroxidation and 8-hydroxydeoxyguanosine formation in rats fed fish oil with different levels of vitamin E. J Nutr Sci Vitaminol 41: 61–72.
Craven PA, DeRubertis FR, Kagan VE, Melhem M, Studer RK 1997 Effects of supplementation with vitamin C or E on albuminuria, glomerular TGF-β, and glomerular size in diabetes. J Am Soc Nephrol 8: 1405–1414.
Sime PJ, Xing Z, Graham FL, Csaky KG, Gauldie J 1997 Adenovector-mediated gene transfer of active transforming growth factor-β1 induces prolonged severe fibrosis in rat lung. J Clin Invest 100: 768–776.
Acknowledgements
The authors thank Betty Timozek for secretarial assistance, Rosalind Bradley, M.Div., for editorial assistance and Linda Benson, M.P.H., and Kenley Ward, B.A., for laboratory assistance.
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Supported by National Institutes of Health T32 DK07526 and R01 DK50419. Hoffmann-LaRoche Inc., Nutley, NJ, funded the α-tocopherol measurements.
James C. M. Chan, M.D., Nephrology Division, Department of Pediatrics, Virginia Commonwealth University's Medical College of Virginia, P.O. Box 980498, Richmond, VA 23298–0498.
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Kuemmerle, N., Chan, W., Krieg, R. et al. Effects of Fish Oil and α-Tocopherol in Immunoglobulin A Nephropathy in the Rat. Pediatr Res 43, 791–797 (1998). https://doi.org/10.1203/00006450-199806000-00012
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DOI: https://doi.org/10.1203/00006450-199806000-00012