Docosahexaenoic Acid and Eicosapentaenoic Acid, but Not α-Linolenic Acid, Suppress Deoxynivalenol-Induced Experimental IgA Nephropathy in Mice

Abstract

Diets enriched in the (n-3) PUFAs, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and their precursor alpha-linolenic acid (ALA), were evaluated for efficacy in ameliorating the development of IgA nephropathy (IgAN) induced in mice by the mycotoxin deoxynivalenol (DON). The effects of DON were compared in mice that were fed for 18 wk with AIN-93G diets containing 1) 10 g/kg corn oil plus 60 g/kg oleic acid (control); 2) 10 g/kg corn oil plus 35 g/kg oleic acid and 25 g/kg DHA-enriched fish oil (DHA); 3) 10 g/kg corn oil plus 33 g/kg oleic acid and 27 g/kg EPA-enriched fish oil (EPA); and 4) 10 g/kg corn oil plus 37 g/kg oleic acid and 23 g/kg DHA + EPA (1:1) enriched fish oil (DHA + EPA). The DHA, EPA and DHA + EPA diets attenuated induction by dietary DON (10 mg/kg) of serum IgA and IgA immune complexes, kidney mesangial IgA deposition, and ex vivo IgA secretion by spleen cells. Consumption of the DHA + EPA diet for 8 wk significantly abrogated the DON-induced gene expression of interleukin (IL)-6, a requisite cytokine for DON-induced IgA nephropathy, in spleen and Peyer's patches. Finally, incorporation of ALA-containing flaxseed oil up to 60 g/kg in the AIN-93G diet did not affect DON-induced IgA dysregulation in mice. Taken together, both DHA and EPA, but not ALA, ameliorated the early stages of IgAN, and these effects might be related to a reduced capacity for IL-6 production.

Acute Changes in Dietary ω-3 and ω-6 Polyunsaturated Fatty Acids Have a Pronounced Impact on Survival following Ischemic Renal Injury and Formation of Renoprotective Docosahexaenoic Acid-Derived Protectin D1

“…This recommendation came forth after population studies and clinical trials had demonstrated that dietary fish oils, enriched in DHA and EPA, are cardio-and renoprotective and that DHA, in particular, has antiinflammatory and immune regulatory actions (7, 8, 46 -49). Our present findings with mice underscore the striking impact of even short-term dietary PUFA manipulation in the sequelae of acute ischemic renal injury and are in agreement with experimental and clinical studies that provide a strong rationale for a beneficial role of increasing the -3 PUFA/ -6 PUFA ratio in renal diseases (6,8,46,47,50). Our finding that mice on a corn oil diet (-3 PUFA ϭ 2% of total fat), unlike mice on a fish oil diet (-3 PUFA ϭ 28% of total fat) or the standard rodent diet (-3 PUFA ϭ 7% of total fat), had 100% mortality due to IRI provides experimental support for meta-analyses that show an inverse correlation with cardiovascular disease, coronary heart disease, and stroke mortality in human populations and their dietary intake of -3 PUFA and -6 PUFA; namely, countries with the lowest -3 PUFA and highest -6 PUFA dietary intake appear to have the highest risk for disease mortalities (45).…”

“…In stark contrast, acute dietary decrease in -3 PUFA and concomitant increase in -6 PUFA was associated with worsened outcome of IRI and a remarkable impact on mortality. In addition to our study, independent reports provide evidence that -3 PUFA in general are renoprotective in ischemic injury, namely that dietary supplementation with EPA and DHA ameliorates ischemic ARF in dogs (13) and that systemic treatment with DHA alone can ameliorate ischemic ARF and protect renal function in mice (12,50).…”

Truncated deoxynivalenol-induced splenic immediate early gene response in mice consuming (n-3) polyunsaturated fatty acids

“…The resultant control and (n-3)-PUFA diets contained (n-6)/(n-3) ratios of 16:1 and 1:18, respectively. This (n-3)-PUFA diet has been previously shown to be effective in increasing DHA in liver phospholipids from 9% to 23% and EPA from 0% to 12% while decreasing arachidonic acid from 23% to 6% [22].…”

“…Recently, we have observed that consumption of menhaden fish oil or DHA-and EPA-enriched oils attenuates DON-induced serum IgA elevation and IgA deposition in mice [21,22]. These preclinical findings are valuable because they suggest that consumption of (n-3)-PUFAs might also have potential value for early intervention and prophylaxis in persons with a familial history of IgAN or in patients diagnosed to be at an early stage of IgAN.…”

Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis

“…To confirm DHA phospholipid incorporation after 8 weeks of DFO consumption, hepatic lipid fractions were extracted and analyzed by gas chromatography (GC) as previously described (33,34).…”