Flaxseed oil and alpha-lipoic acid combination reduces atherosclerosis risk factors in rats fed a high-fat diet
Flaxseed oil and alpha-lipoic acid combination reduces atherosclerosis risk factors in rats fed a high-fat diet
Year: 2012
Authors: Xu, J. Yang, W. Deng, Q. Huang, Q. Yang, J. Huang, F.
Publication Name: Lipids in Health & Dis.
Publication Details: Volume 11; Page 148
Abstract:
Atherosclerosis is a major manifestation of the pathophysiology underlying cardiovascular disease. Flaxseed oil (FO) and alpha lipoic acid (LA) have been reported to exert potential benefit to cardiovascular system. This study tried to assess the effect of supplement of FO and LA combination on the atherosclerosis risk factors in rats fed a high-fat diet.LA was dissolved in flaxseed oil to a final concentration of 8 g/kg (FO plus LA) when used. The rodent diet contained 20 percent fat whose source was lard (HFD) or 75 percent lard and 25 percent FO plus LA (LFO plus LA) or 50 percent lard and 50 percent FO plus LA (MFO plus LA) or FO plus LA (HFO plus LA). Animals were fed for 10 weeks and then killed for blood collection. Supplement of FO and LA combination significantly enhanced plasma antioxidant defense capacities, as evaluated by the marked increase in the activities of SOD, CAT and GPx as well as the level of GSH, and the significant reduction in lipid peroxidation. Simultaneous intake of FO and LA also reduced plasma TG, TC and LDLC contents and elevated the ratio of HDLC to LDLC. Besides, in parallel with the enhancement of FO and LA combination, plasma IL6 and CRP levels were remarkably reduced. Supplement of FO and LA combination may contribute to prevent atherogenesis by improving plasma oxidative stress, lipid profile and inflammation. (Authors abstract)
Flaxseed oil (FO) is the main component of the flaxseed and one of the world's most important vegetable sources of alpha linolenic acid (ALA, 18:3n3). As a nutritionally essential polyunsaturated fatty acid (PUFA), ALA can act as the precursor of longer chain n3 PUFA(EPA and DHA) or compete with linoleic acid or direct interaction with ion channels and nuclear receptors, and thus may exert various biological functions in the human body, such as accelerating brain growth in preterm and neonates and, antiarrhythmic functions and neuroprotective functions. In addition, ALA is also reported to have beneficial effects on blood lipid profiles and inflammation, which may responsible for the protection against CVD bestowed by FO. However, on the other hand, since ALA is highly susceptible to oxidation, FO addition leads to a significantly higher tendency toward plasma lipid peroxidation, which may have an adverse effect on the protection of cardiovascular system.
alpha lipoic acid (LA), also referred to as thioctic acid, is a disulfide compound that is found naturally in mitochondria as the coenzyme for pyruvate dehydrogenase and alpha ketoglutarate thus serves a critical role in mitochondrial energy metabolism. LA has gained considerable attention as an excellent antioxidant to reduce oxidative stress and is fat- and water-soluble, which makes it effective against a broader range of free radicals. The effects of a simultaneous intake of FO and LA on cardiovascular system have not been investigated. Therefore, the objectives of this study were to determine that whether FO and LA combination can reduce atherosclerosis risk factors in rats fed a high-fat diet.
The imbalance between cellular production of free radicals and the antioxidant defense is referred to as oxidative stress. The relative excessive production of free radicals can attack all types of biomolecules, which may affect oxidation of low density lipoproteins and lead to the destruction of cellular components and thus initiates the processes of atherogenesis. Free radicals are key mediators of various signaling pathways which underlie vascular inflammation in atherogenesis. An efficient antioxidant defense mechanism (enzymatic and non-enzymatic) is able to counteract the deleterious effects of oxidative stress. The primary antioxidant enzymes in mammals include SOD which converts superoxide to hydrogen peroxide, GPx and CAT which are responsible for converting hydrogen peroxide to water. In the present study, FO and LA combination markedly increased the plasma activities of these antioxidant enzymes (SOD, CAT and GPx) as well as GSH level, which resulted in pronounced enhancement of plasma T-AOC. As a consequence, plasma lipid peroxidation levels significantly declined with the supplement of FO and LA combination.
In the present study, FO and LA combination decreased the plasma TG, TC and LDL-C levels, and both of them contributed to these beneficial changes. ALA and LA have both been reported to suppress the expression and activities of many hepatic fatty acid syntheses such as fatty acid synthase (FAS), malic enzyme and glucose 6-phosphate dehydrogenase and hence decrease fatty acid synthesis in liver. On the other hand, ALA sharply enhances hepatic peroxisomal and mitochondrial fatty acid oxidation rate by increasing the expression and activities of a series of fatty acid oxidation enzymes. Although simultaneous intake of FO and LA did not markedly affect plasma HDLC level in the present study, the significant increase in the ratio of HDL to LDL cholesterol still meant that the combination of FO and LA had a marked protective effect with respect to atherosclerosis. In summary, the combination of FO and LA is effective in amelioration of oxidative stress, lipid profile and inflammation of plasma in rats fed a high-fat diet. These results suggested that supplement of FO and LA combination might contribute to prevent atherogenesis and then decrease the incidence of CVD. (Editors comments)
