Dietary flax oil reduces renal injury, oxidized LDL content, and tissue n−6/n−3 FA ratio in experimental polycystic kidney disease

Abstract

As whole flaxseed is beneficial in the treatment of experimental renal disease, we undertook a study to determine whether previously documented benefits of whole flaxseed could be reproduced with dietary low-lignan flax oil (FO), a rich source of alpha-linolenic acid, in experimental polycystic kidney disease. Male offspring of Han:SPRD-cy heterozygous rats were fed a synthetic diet containing FO or corn oil (CO) for 8 wk from the time of weaning. Renal inflammation, fibrosis, proliferation, cystic change, and oxidized-LDL were assessed morphometrically. Hepatic and renal lipid composition was assessed using GC. FO feeding produced hepatic and renal enrichment of n-3 PUFA and an increase in C18:>C18 PUFA ratios (18-carbon PUFA compared to longer-chain PUFA), with a reduction in proportion of hepatic long-chain PUFA. The FO-based diet was associated with lower mean cystic change by 29.7% (P = 0.018), fibrosis by 21.7% (P = 0.017), macrophage infiltration by 31.5% (P < 0.0001), epithelial proliferation by 18.7% (P = 0.0035), and ox-LDL detection by 31.4% (P < 0.0001) in Han:SPRD-cy heterozygotes. Serum creatinine was significantly lower in FO-fed diseased animals. A small hypocholesterolemic effect was noted in all animals fed FO. FO feeding moderates renal injury, modifies the profile of substrates available for elongation to eicosanoid precursors, and inhibits the elongation of C18 PUFA in this model. The consumption of FO-based products may prove a more practical way of obtaining health benefit than attempts to increase dietary content of unrefined seed.

Dietary Flax Oil During Pregnancy and Lactation Retards Disease Progression in Rat Offspring With Inherited Kidney Disease

“…The formalin-fixed left kidney was embedded in paraffin, sectioned at 5 m and was processed using our previously described methods for histologic and immunohistochemical analyses (7,19). Transverse tissue sections (including cortex, medulla and papilla) were stained with hematoxylin and eosin for cyst area measurement and those for quantitative analysis of fibrosis with Sirius red (in adaptation of Masson's trichrome stain) which permits image analysis measurement using a standard incandescent microscope light source.…”

“…After being captured using a SPOT junior CCD camera by random stage movement through the sections, images were analyzed using the Image Pro version 4.5 package (Media Cybernetics, Silver Spring, MD) as described previously (7,19). An average of 25 measurements starting from a random field of tissue section from kidney cross-sections were collected for all histomorphometric analyses.…”

“…The portion of tissue section occupied by tubular lumen or cyst was determined for cyst area measurements. Renal interstitial fibrosis and oxidant injury were measured by densitometry, while the number of cells stained positive for PCNA as well as macrophages were counted using the Image Pro version 4.5 package (Media Cybernetics, Silver Spring, MD) as described previously (7,19). Renal cyst area measurements were expressed relative to kidney weight-to-body weight ratios.…”

“…Dietary flax (rich in n-3 fatty acids) reduces renal interstitial fibrosis, cystic growth and renal macrophage infiltration in this model of hereditary kidney disease when given in the postweaning period of life (7,18). The aim of the current study was to determine whether flax oil supplementation during pregnancy and lactation would slow the progression of renal disease in offspring of Han: SPRD-cy rats.…”

“…Dietary interventions such as altering dietary fat sources slow the progression of chronic renal disease. Dietary n-3 fatty acids from fish and flax sources have been shown to be reno-protective, particularly in renal injury that has an immune and/or inflammatory component (3)(4)(5)(6)(7). These protective effects of n-3 fatty acids on renal disease progression in humans or animal models have been demonstrated in adult or weanling animals.…”