Research Articleα-Linolenic acid (ALA) is an anti-inflammatory agent in inflammatory bowel disease
Introduction
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that includes ulcerative colitis and Crohn's disease. Worldwide, the prevalence of IBD is on the rise, particularly in the industrialized countries of the Western World [1], [2]. Over 1 million people in America suffer from IBD and its symptoms, which include diarrhea, loss of appetite, joint pains, sores in the anal area, rectal bleeding and fistulas. The etiology of the disease is poorly understood; however, it is assumed that the disease is controlled by multiple environmental, genetic and immune-regulatory factors [3], [4], [5].
The current drug regimens available for IBD patients include a combination of steroids, immunosuppressants and antibiotics. These drugs cause side effects, and in many cases, complications develop [3], [6]. In an attempt to overcome these challenges, a large number of studies have been carried out in order to discover a more effective and safe treatment for IBD, frequently by examining different anti-inflammatory agents.
Omega-3 (n-3) polyunsaturated fatty acids (PUFA) exhibit anti-inflammatory properties due to the activity of eicosanoids derived from eicosapentaenoic acid [EPA, 20:5(n-3)], which can be synthesized after ingestion from α-linolenic acid [ALA, 18:3(n-3)]. These eicosanoids exhibit properties opposite to those derived from arachidonic acid [AA, 20:4(n-6)]. The eicosanoids that are derived from AA, including prostaglandin PGE2, thromboxane TXA2 and leukotriene LTB4, are potent vessel constrictors, vasodilatation agents and platelet aggregators. Alternatively, eicosanoids that are formed from EPA, including prostaglandin PGE3, thromboxane TXA3 and leukotriene LTB5, are weaker platelet aggregators; they exhibit a lower chemotactic activity and are less pro-inflammatory mediators [7], [8], [9], [10]. Numerous studies suggested a protective role of the dietary intake of (n-3) PUFA in IBD due to their anti-inflammatory properties [7], [9], [11], [12], [13], [14], [15].
Recent experimental studies in rats with experimental colitis, induced by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS model), have documented that treatment with (n-3) PUFA reduces mucosal damage as assessed by biochemical and histological markers of inflammation [11]. Fish oil, rich in EPA and docosahexaenoic acid (DHA) (n-3) PUFA, has been demonstrated as a supplement that reduces colonic damage and inflammatory markers in numerous animal studies [12], [13]. Most of the studies that investigated (n-3) fatty acids have focused on fish oil. Few studies have examined the effect of plant-derived oils rich in ALA, like flaxseed and perilla oils, on various inflammatory markers. The effect of a flaxseed oil-based diet on tumor necrosis factor α (TNF-α) and interleukin IL-1β synthesis was examined in healthy volunteers. Use of flaxseed oil in domestic food preparation for 4 weeks inhibited TNF-α and IL-1β production by more than 30% [16]. Another experiment investigated the effect of a perilla oil-enriched diet on mucosal levels of leukotrienes (LTs) in rats with experimental colitis induced by dextran sulfate sodium (DSS). The production of LTs from the colonic mucosa in the experimental group was significantly lower than that of controls [17]. Despite the small number of studies using plant-derived oils rich in ALA, there is a growing body of evidence suggesting that ALA alone might have an anti-inflammatory effect [18], [19], [20]. Therefore, the aim of this research was to study the effect of two different sources of (n-3) PUFA, fish and plant-derived oils, in two animal models of colitis and to determine whether the different (n-3) PUFA-enriched diets could ameliorate the inflammatory status in colitis with the same efficacy. In addition, a series of studies have demonstrated that vitamin A deficiency (VAD) alters and broadens inflammatory responses while supplementation of the vitamin activates anti-inflammatory cascades [21]. Vitamin A is a lipid-soluble antioxidant, a regulator of epithelial proliferation and differentiation and is vital for optimal immune function. Studies show that dietary VAD has a profound effect on the membrane fatty acid profile in rat tissues. Moreover, a combined vitamin A and (n-3) fatty acid deficiency dramatically shifts the balance of n-3/n-6 PUFA in rat liver and colon tissues and alters the entire cell membrane PUFA profile [22]. Considering the protective properties of vitamin A and the existing evidence, we aimed to ascertain whether an ALA-enriched diet with vitamin A supplementation had a synergistic and more potent effect on reducing inflammatory markers.
Section snippets
Materials and methods
This study received ethical approval from the ethics committee of the Hebrew University for studies involving animals and was carried out in a full compliance with The Hebrew University Policy on Animal Use and Care.
Results
This study examined the effect of fish and plant-derived oils in two animal models of colitis and in in vitro Caco-2 model to determine whether the ALA-enriched diets could ameliorate the inflammatory status in colitis and to compare the ALA-rich SO and FO anti-inflammatory effects. The main differences among the three diets were the contents of linoleic acid (LA) [18:2(n-6)], ALA [18:3(n-3)], EPA [20:5(n-3)], and DHA [22:6(n-3)]. Levels of saturated fatty acids (SFA) also differed among the
Discussion
To date, numerous studies suggest a protective role of the dietary intake of (n-3) PUFA in IBD due to their anti-inflammatory properties both in animal models of colitis and in humans [11], [12], [13], [16], [17]. Most of the studies focused on fish oil, rich in EPA and DHA, while only a few have been performed using plant-derived oils rich in ALA. The accumulating findings emphasize the importance of (n-3) PUFA in the diet. However, it is unclear whether the amount of (n-3) PUFA leads to their
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