Effects of Flaxseed and Flax Oil Diets in a Rat-5/6 Renal Ablation Model.
Effects of Flaxseed and Flax Oil Diets in a Rat-5/6 Renal Ablation Model.
Year: 1995
Authors: A J Ingram, A Parbtani, W F Clark, E Spanner, M W Huff, D J Philbrick, B J Holub.
Publication Name: Amer. J. Kidney Dis.
Publication Details: Volume 25; Number 2; 320.
Abstract:
The renal ablation rat model mimics human renal diseases associated with glomerular scarring and a progressive decline in renal function. In this model, rats are subjected to 5/6 nephrectomy which involves excision of one kidney and infarction of two thirds of the other resulting in a reduction in functional nephrons below a critical number. Remaining nephrons enlarge causing an increase in single-nephron filtration rate and intraglomerular pressure. Systemic and intraglomerular hypertension, proteinura and glomerulosclerosis follow leading to kidney failure. Inflammation, increases in vasoconstrictive eicosanoids, and lipid abnormalities have been implicated in the progression of renal failure. Previous research by these investigators showed beneficial effects of ALA and lignans from flaxseed in the MRL/lpr lupus mouse, a model for progressive kidney disease. The authors speculated that flaxseed may have positive effects in lupus nephritis due to the antihypertensive, hypolipidemic, anti-inflammatory and immunosuppressive characteristics of ALA. In addition, the effects of flaxseed may be due to lignans which are potent platelet activating factor (PAF)-receptor antagonists. PAF is a major participant in the activation and propagation of inflammation. The objective of this study was to assess the effects of flaxseed (ALA plus lignans) and flaxseed oil (ALA only) in the rat renal ablation model. Rats were subjected to 5/6 nephrectomy, fed a regular laboratory diet (RLD) for 1 week, then divided into three groups. They received either the RLD (n=8), a 15% flaxseed diet (n = 8), or a 15% flaxseed oil diet (n = 7). Blood pressure, proteinuria, glomerular filtration rate (GFR), and urinary PGEs (TXB2 and 6-keto PGF1-alpha) were measured before surgery and at 1 week (before dietary allotment) and 20 weeks postnephrectomy. At this point, blood for plasma lipids and kidneys for histology and tissue PL analyses were obtained. The results showed that hypertension and hyperlipidemia were prevented by the flax diets. Blood pressure increased progressively in the RLD group but not in the flaxseed or flaxseed oil diet groups. Plasma TGs and TC increased in all groups, but the increase was significantly attenuated by both flax diets. Both flax diets reduced the progression of renal disease as measured by proteinuria and GFR. Proteinuria increased 1 week postsurgery and continued to increase in the RLD groups but not in the flaxseed or flaxseed oil diet groups. GFR decreased progressively, but this decline in renal function was attenuated significantly by the flaxseed and flaxseed oil diets. Both flax diets prevented glomerulosclerosis and mesangial expansion. Renal ALA was increased by both flax diets (flaxseed oil > flaxseed). Renal EPA increased in the flaxseed oil group only. The flaxseed group showed higher renal AA levels than the flaxseed oil and RLD groups which the authors attributed to the higher levels of LA from the corn oil used in this diet. Total omega-3 FA increased twofold to threefold in the flaxseed oil group compared with the two other groups. Total SFA were lower and PUFAs were increased in both flax diet groups. A progressive increase in urinary TXB2 occurred in the RLD group but not in the flaxseed group. TXB2 levels decreased in the flaxseed oil group. Reduction in the synthesis of TXB2 has been associated with a decrease in glomerular capillary pressure, thrombotic events and the progression of renal disease in this model. The decline in the ratio of PGF1alpha/TXB2 associated with renal disease was prevented by the flaxseed oil diet. The authors concluded that dietary flaxseed and flaxseed oil attenuated the decline in renal function and reduced glomerular injury in the rat-5/6 renal ablation model. In addition, both flaxseed and flaxseed oil produced beneficial effects on blood pressure, plasma lipids, and urinary PGEs. While the results of the study did not prove any specific synergistic effects of the constituents of the flaxseed diet, the investigators indicated that favorable effects of flax-derived ALA with or without lignans in the rat-5/6 renal ablation model are supported by this experiment.
