Antioxidant and anti-inflammatory effect of conjugated linolenic acid isomers against streptozotocin-induced diabetes

The present study was undertaken to evaluate the effect of α-eleostearic acid and punicic acid, two isomers of conjugated linolenic acid (CLnA) present in bitter gourd (Momordica charantia) and snake gourd oil (Trichosanthes anguina), respectively, against oxidative stress, inflammatory challenge and aberration in erythrocyte morphology due to streptozotocin (STZ)-induced diabetes. Male albino rats were divided into four groups consisting of eight animals in each group. The first group served as control and diabetes was induced in rats in groups 2-4 by a single intraperitoneal injection of STZ. Moreover, rats in groups 3 and 4 were treated with 0·5?% of α-eleostearic acid and 0·5?% of punicic acid of the total lipid given, respectively, by oral administration once per d. After administration, CLnA isomers had significantly reduced oxidative stress, lipid peroxidation and restored antioxidant and pro-inflammatory enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, reduced glutathione, NO synthase level in pancreas, blood and erythrocyte lysate. The ferric reducing antioxidant power (FRAP) assay of plasma showed that CLnA treatment caused improvement in the FRAP value which was altered after STZ treatment due to an increased level of free radicals. Expression of inflammatory cytokines such as TNF-α and IL-6 in blood and expression of hepatic NF-κB (p65) increased significantly after STZ treatment due to increased inflammation which was restored with the administration of CLnA isomers. From the obtained results, it could be concluded that α-eleostearic acid and punicic acid showed potent antioxidant and anti-inflammatory activity with varying effectivity.     

Comparative study of hypocholesterolemic and hypolipidemic effects of conjugated linolenic acid isomers against induced biochemical perturbations and aberration in erythrocyte membrane fluidity

Aim of study

The purpose of the study was to evaluate hypolipidemic and hypocholesterolemic activities of conjugated linolenic acid (CLnA) isomers, present in bitter gourd and snake gourd seed, in terms of amelioration of plasma lipid profile, lipoprotein oxidation and erythrocyte membrane fluidity after oral administration.

Methods

Male albino rats were divided into six groups. Group 1 was control, and others were induced with oxidative stress by oral gavage of sodium arsenite (Sa). Group 2 was kept as treated control, and groups 3–6 were further treated with different oral doses of seed oils to maintaining definite concentration of CLnA isomers (0.5 and 1.0% of total lipid for each CLnA isomer).

Results

CLnA isomers normalized cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride contents in plasma and body weight of experimental rats and decreased cholesterol synthesis by reducing hepatic HMG-CoA reductase activity. Administration of Sa caused alteration in erythrocyte membrane fluidity due to increase in cholesterol and decrease in phospholipid content. Tissue cholesterol and lipid contents were also increased by Sa administration. These altered parameters were reversed by experimental oil administration. Protective effect of CLnA isomers on erythrocyte morphology was observed by atomic force microscopy (AFM). Fatty acid composition of erythrocyte membrane showed decrease in polyunsaturated fatty acid (PUFA) and increase in arachidonic acid content after Sa administration, which was normalized with the treatment of these oils. Supplementation of CLnA isomers restored erythrocyte membrane (EM) lipid peroxidation and lipoprotein oxidation.

Conclusion

CLnA isomers, present in vegetable oils, showed potent hypolipidemic and hypocholesterolemic activities against biochemical perturbations.     

A Three-Month Consumption of Eggs Enriched with ω-3, ω-5 and ω-7 Polyunsaturated Fatty Acids Significantly Decreases the Waist Circumference of Subjects at Risk of Developing Metabolic Syndrome: A Double-Blind Randomized Controlled Trial

Alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), rumenic acid (RmA), and punicic acid (PunA) are claimed to influence several physiological functions including insulin sensitivity, lipid metabolism and inflammatory processes. In this double-blind randomized controlled trial, we investigated the combined effect of ALA, DHA, RmA and PunA on subjects at risk of developing metabolic syndrome. Twenty-four women and men were randomly assigned to two groups. Each day, they consumed two eggs enriched with oleic acid (control group) or enriched with ALA, DHA, RmA, and PunA (test group) for 3 months. The waist circumference decreased significantly (−3.17 cm; p < 0.001) in the test group. There were no major changes in plasma insulin and blood glucose in the two groups. The dietary treatments had no significant effect on endothelial function as measured by peripheral arterial tonometry, although erythrocyte nitrosylated hemoglobin concentrations tended to decrease. The high consumption of eggs induced significant elevations in plasma low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol (p < 0.001), which did not result in any change in the LDL/HDL ratio in both groups. These results indicate that consumption of eggs enriched with ALA, DHA, RmA and PunA resulted in favorable changes in abdominal obesity without affecting other factors of the metabolic syndrome.     

Protective effect of conjugated linolenic acid isomers present in vegetable oils against arsenite-induced renal toxicity in rat model

ObjectiveThe aim of the present study was to investigate the protective effect of conjugated linolenic acid (CLnA), present in vegetable oils against arsenite-induced renal oxidative stress.MethodsAlbino rats were divided into six groups. Group 1 was control and group 2 was treated with sodium arsenite (Sa; 10 mg/kg BW). Rats in groups 3 and 4 were treated with mixture of α-eleostearic acid and punicic acid (1:1) (0.5% and 1.0%, respectively), whereas rats in the groups 5 and 6 were treated with 0.5% of α-eleostearic acid and 0.5% of punicic acid, respectively, along with Sa by oral gavage once daily.ResultsResults revealed that activity of antioxidant enzymes and total reduced glutathione content, total protein content, and phospholipid content in kidney were decreased significantly in arsenite-treated group compared with control. Activity of nitric oxide synthase, peroxidation of lipid, protein oxidation, total cholesterol content, total lipid content of kidney, and plasma creatinine level were increased significantly (P < 0.05) in arsenite-treated rats compared with control. Fatty-acid composition of renal lipids showed significant decrease in monounsaturated fatty acid, polyunsaturated fatty acid (PUFA) content, and increase in saturated fatty acid content due to oxidative stress. PUFA such as γ-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid decreased significantly with significant (P < 0.05) increase in arachidonic acid content after Sa treatment. Administration of blended product of both the isomers caused better restoration of renal fatty acids and other altered parameters.ConclusionCLnA isomers caused amelioration of renal oxidative stress and the isomers showed synergistic activity.     

共轭亚麻酸在体外细胞中的代谢与整合研究

目的以富含石榴酸(共轭亚麻酸异构体之一,含量达75.5%)的石榴籽油为材料,研究共轭亚麻酸在体外培养的肝癌细胞系HepG2中的代谢和整合状况。方法以含10μmol/L石榴酸处理HepG2 24h后进行脂肪酸分析。结果细胞中出现新的代谢产物,进一步通过GC-MS确认代谢产物为9顺,11反-共轭亚油酸(c9,t11-18:2),c9,t11-18:2,含量占总脂肪酸的2.78%,石榴酸含量占总脂肪酸的0.67%。结论石榴酸代谢产物酸能在体外细胞内整合,且整合到细胞内的石榴酸大部分进一步代谢成为c9,t11-18:2。     

铁离子与铁死亡:衰老研究领域的新大陆

铁死亡是新发现的形态、生化、遗传上有别于传统死亡方式的调节性细胞坏死方式,以铁离子依赖的脂质过氧化过程为标识,在多种疾病（如神经退行性疾病和癌症）进程中发挥着至关重要的作用。在铁死亡过程中,铁离子扮演着关键性的角色（包括构成脂质过氧化酶和催化细胞内的氧化还原反应等）;且铁离子的吸收、运输、储存、利用等过程均会影响铁死亡的敏感性。随着铁离子和铁死亡关系研究的深入,衰老研究领域也不断取得新进展:在衰老过程中,神经细胞内铁离子的过度积累触发铁死亡,导致神经退行性疾病的发生;而衰老细胞内过量的铁离子则可以阻碍自噬,逃避铁死亡,加速衰老过程。毋庸置疑,铁离子与铁死亡在衰老过程中神秘的关系为衰老研究领域开辟了新大陆。然而,目前国内未见相关综述报道,本文将近年来铁死亡和铁离子在衰老研究中的最新进展做一综述,以期为铁离子与铁死亡在衰老过程中作用机制的研究提供新思路。     

γ-亚麻酸对人癌细胞蛋白质合成和脂质过氧化的影响

本文报告γ-亚麻酸对体外培养人癌细胞生长、蛋白质合成和脂质过氧化的影响。结果表明,γ-亚麻酸抑制人癌细胞生长和20、30kD蛋白质合成,并增强培养人结肠癌细胞的脂质过氧化,α-生育酚则部分抵消γ-亚麻酸的作用。上述结果提示,γ-亚麻酸的抗肿瘤效果可能是由于其对蛋白质合成的抑制作用,而蛋白质合成的抑制则可能是由增强的脂质过氧化所致。     

Beef conjugated linoleic acid isomers reduce human cancer cell growth even when associated with other beef fatty acids

Although many data are available concerning anticarcinogenic effects of industrial conjugated linoleic acid (CLA), few studies have reported the antitumour properties of CLA mixtures originating from ruminant products. The aim of the present study was to investigate the in vitro antiproliferative effects of beef CLA mixtures on breast, lung, colon, melanoma and ovarian human cancer cell lines. For this purpose, four fatty acid (FA) extracts prepared from beef lipid and varying in their CLA composition, their corresponding purified CLA-enriched fractions, and mixtures of pure synthetic CLA, the composition of which reproduced that of the four selected beef samples, were tested on cancer cell lines. Cancer cells were exposed for 48 h to medium containing 100 microm-FA and their proliferation was determined by quantifying cellular DNA content (Hoechst 33342 dye). Compared with cells incubated without FA, the number of cancer cells was reduced from 25 to 67 % (P<0.0001) following FA treatment. Antiproliferative effects of CLA mixtures varied in magnitude according to the source of FA, the CLA composition and the cell lines. CLA mixtures naturally present in beef inhibited the proliferation of human cancer cell lines, a high content in cis-trans isomers allowing the most important antiproliferative effect. Beef total FA exhibited a greater growth-inhibitory activity than their corresponding CLA-enriched fractions. These results suggested that either beef FA other than beef CLA could possess antiproliferative properties and/or the existence of complementary effects of non-conjugated FA and CLA, which could favour the antiproliferative properties of beef total FA.     

Bioactive dietary long-chain fatty acids: emerging mechanisms of action

The plasma membranes of all eukaryotic cells contain heterogeneous self-organising intrinsically unstable liquid ordered domains or lipid assemblies in which key signal transduction proteins are localised. These assemblies are classified as 'lipid rafts' (10-200 nm), which are composed mostly of cholesterol and sphingolipid microdomains and therefore do not integrate well into the fluid phospholipid bilayers. In addition, caveolae represent a subtype of lipid raft macrodomain that form flask-shaped membrane invaginations containing structural proteins, i.e. caveolins. With respect to the diverse biological effects of long-chain PUFA, increasing evidence suggests that n-3 PUFA and perhaps conjugated fatty acids uniquely alter the basic properties of cell membranes. Because of its polyunsaturation, DHA and possibly conjugated linoleic acid are sterically incompatible with sphingolipid and cholesterol and, therefore, appear to alter lipid raft behaviour and protein function. The present review examines the evidence indicating that dietary sources of n-3 PUFA can profoundly alter the biochemical make up of lipid rafts/caveolae microdomains, thereby influencing cell signalling, protein trafficking and cell cytokinetics.     

硼酸对顺铂致体外人胚肾细胞毒性保护作用

目的 体外研究硼酸对顺铂所致肾毒性的保护作用,并探讨其可能机制.方法 体外培养人胚肾293(HEK293)细胞,四甲基偶氮噻唑蓝(MTT)法观察硼酸对顺铂细胞毒性的保护作用,硫代巴比妥酸反应产物测定法观察硼酸对顺铂引起的脂质过氧化的影响,荧光比色法观察硼酸对顺铂诱导的谷胱甘肽耗竭的影响.结果 硼酸能明显抑制顺铂对HEK293细胞的细胞毒性作用,24h半数抑制浓度(IC50)值由(0.38±0.04)mmol.L升高为(0.87±0.10)mmol.L,2者之间差异有统计学意义(P＜0.05);硼酸能明显抑制顺铂所致脂质过氧化产物的形成.并能提升顺铂引起的还原型谷胱苷肽(GSH)含量的下降.结论 硼酸能抑制顺铂所致HEK293细胞的细胞毒性,其机制可能与其抗氧化作用和清除自由基活性有密切关系.     

Dietary effect of pomegranate seed oil rich in 9cis, 11trans, 13cis conjugated linolenic acid on lipid metabolism in obese,hyperlipidemic OLETF Rats

Conjugated fatty acid, the general term of positional and geometric isomers of polyunsaturated fatty acids with conjugated double bonds, has attracted considerable attention because of its potentially beneficial biological effects. In the present study, dietary effect of pomegranate seed oil rich in punicic acid (9 cis, 11 trans, 13 cis -conjugated linolenic acid; 9c, 11t, 13c-CLNA) on lipid metabolism was investigated in obese, hyperlipidemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After 2 weeks feeding period, OLETF rats revealed obesity and hyperlipidemia compared with their progenitor LETO rats. Feeding of the diet supplemented with 9% safflower oil and 1% pomegranate seed oil (9c, 11t, 13c-CLNA diet) did not affect abdominal white adipose tissue weights and serum lipid levels compared with the diet supplemented with 10% safflower oil (control diet) in OLETF rats. However, the accumulated hepatic triacylglycerol was markedly decreased by 9c, 11t, 13c-CLNA diet in OLETF rats. Activities of hepatic enzymes related to fatty acid synthesis and fatty acid β-oxidation were not altered by 9c, 11t, 13c-CLNA diet. Levels of monounsaturated fatty acid (MUFA), major storage form of fatty acid, in serum triacylglycerol were markedly higher in obese, hyperlipidemic OLETF rats than in lean LETO rats. In addition, 9c, 11t, 13c-CLNA diet significantly decreased MUFA levels in OLETF rats. This is the first study showing that 9c, 11t, 13c-CLNA suppresses delta-9 desaturation in vivo, and we suggest that the alleviation of hepatic triacylglycerol accumulation by 9c, 11t, 13c-CLNA diet was, at least in part, attributable to the suppression of delta-9 desaturation in OLETF rats.     

Effect of functional buffalo cheese on fatty acid profile and oxidative status of liver and intestine of mice

The objective of this study was to determine the influence of administration of buffalo dairy products on lipid content and conjugated linoleic acid (CLA) incorporation on liver and intestine of mice. Buffalo cheeses were selected according to nutritional properties and CLA content. Cheeses were previously manufactured using as adjunct culture bacteria with probiotic or technological properties. BALB/c mice were fed for 28 days, and then a single dose of 1,2-dimethylhydrazine (DMH) as oxidant agent was administered before the influence of diet and DMH on antioxidant status in tissues was evaluated. Mice fed buffalo cheese showed the highest body weight gain (P?相似文献   

The Regulatory Roles of Polysaccharides and Ferroptosis-Related Phytochemicals in Liver Diseases

Liver disease is a global health burden with high morbidity and mortality worldwide. Liver injuries can develop into severe end-stage diseases, such as cirrhosis or hepatocellular carcinoma, without valid treatment. Therefore, identifying novel drugs may promote liver disease treatment. Phytochemicals, including polysaccharides, flavonoids, alkaloids, and terpenes, are abundant in foods and medicinal plants and have various bioactivities, such as antioxidation, immunoregulation, and tumor killing. Recent studies have shown that many natural polysaccharides play protective roles in liver disease models in vitro and in vivo, such as fatty liver disease, alcoholic liver disease, drug-induced liver injury, and liver cancer. The mechanisms of liver disease are complex. Notably, ferroptosis, a new type of cell death driven by iron and lipid peroxidation, is considered to be the key mechanism in many hepatic pathologies. Therefore, polysaccharides and other types of phytochemicals with activities in ferroptosis regulation provide novel therapeutic strategies for ferroptosis-related liver diseases. This review summarizes our current understanding of the mechanisms of ferroptosis and liver injury and compelling preclinical evidence of natural bioactive polysaccharides and phytochemicals in treating liver disease.     

Modification of the Lipid Profile of the Initial Oral Biofilm In Situ Using Linseed Oil as Mouthwash

Lipids are of interest for the targeted modification of oral bioadhesion processes. Therefore, the sustainable effects of linseed oil on the composition and ultrastructure of the in situ pellicle were investigated. Unlike saliva, linseed oil contains linolenic acid (18:3), which served as a marker for lipid accumulation. Individual splints with bovine enamel slabs were worn by five subjects. After 1 min of pellicle formation, rinses were performed with linseed oil for 10 min, and the slabs’ oral exposure was continued for up to 2 or 8 h. Gas chromatography coupled with electron impact ionization mass spectrometry (GC-EI/MS) was used to characterize the fatty acid composition of the pellicle samples. Transmission electron microscopy was performed to analyze the ultrastructure. Extensive accumulation of linolenic acid was recorded in the samples of all subjects 2 h after the rinse and considerable amounts persisted after 8 h. The ultrastructure of the 2 h pellicle was less electron-dense and contained lipid vesicles when compared with controls. After 8 h, no apparent ultrastructural effects were visible. Linolenic acid is an excellent marker for the investigation of fatty acid accumulation in the pellicle. New preventive strategies could benefit from the accumulation of lipid components in the pellicle.     

Ascorbic acid alleviates toxicity of paclitaxel without interfering with the anticancer efficacy in mice

Paclitaxel is used extensively as a chemotherapeutic agent against a broad range of tumors but often leads to the early termination of treatment due to severe toxic side effects. In this study, we hypothesized that ascorbic acid could reduce the toxic side effects without interfering with the anticancer effect of paclitaxel. To demonstrate this, we examined the effect of the combinational treatment of ascorbic acid and paclitaxel using H1299 (a non-small cell lung cancer cell line) and BALB/c mice implanted with or without sarcoma 180 cancer cells. In H1299 cells, the anticancer effects of the combinational treatment with paclitaxel and ascorbic acid were up to 1.7-foldhigher than those of single-agent paclitaxel treatment. In addition, it was shown that the viability of the HEL299 normal cells was up to 1.6-fold higher with the combinational treatment than with paclitaxel treatment alone. In vivo mouse experiments also showed that mice co-treated with paclitaxel and ascorbic acid did not exhibit the typical side effects induced by paclitaxel, such as a reduction in the numbers of white blood cells and red blood cells and the level of hemoglobin (P < .05). The analysis of cancer-related gene expression by quantitative real-time polymerase chain reaction and immunohistochemistry revealed that the combinational treatment suppressed cancer cell multiplication. Taken together, these results suggest that combinational chemotherapy with ascorbic acid and paclitaxel not only does not block the anticancer effects of paclitaxel but also alleviates the cytotoxicity of paclitaxel in vivo and in vitro.     

Conjugated linoleic acid: a functional nutrient in the different pathophysiological components of the metabolic syndrome?

PURPOSE OF REVIEW: Much attention has focused on the therapeutic potential of conjugated linoleic acid with the most abundant isomers being cis-9,trans-11 conjugated linoleic acid and trans-10,cis-12 conjugated linoleic acid. Initial animal studies associated conjugated linoleic acid with beneficial health properties, such as reducing the risk of cancer, diabetes, atherosclerosis, inflammation and obesity. This review has appraised the evidence in relation to the effect of conjugated linoleic acid on components of the metabolic syndrome (clinically or experimentally), in particular, obesity, insulin resistance, atherosclerosis and inflammation. RECENT FINDINGS: More recent human conjugated linoleic acid supplementation studies have often shown conflicting and less convincing health benefits. The marked variation between studies may reflect the isomer-specific effect of the individual conjugated linoleic acid isomers, which can often have opposing effects. Detrimental effects have been observed in some studies, in particular after supplementation with the trans-10,cis-12 conjugated linoleic acid isomer. SUMMARY: Further studies and long-term clinical trials will be required to determine the efficacy and safety of conjugated linoleic acid isomers before conjugated linoleic acid could be considered as a functional nutrient in humans.     

Mechanisms of Anticancer Activity of a Fatty Acid Mixture Extracted from Hen Egg Yolks Enriched in Conjugated Linoleic Acid Diene (CLA) against WM793 Melanoma Cells

The conjugated linoleic acid (CLA) diene is a biologically active compound with proven health-promoting effects. In terms of anticancer properties, it has been shown that CLA reduces the proliferation of cancer cells. In this study, it has been demonstrated that a mixture of fatty acids, isolated from chicken egg yolk enriched in CLA isomers by biofortification, reduces (by 30.5%) the proliferation of human melanoma cancer cells line WM793 to a greater extent than a mixture of fatty acids not containing these isomers. At the same time, the tested fatty acid mixtures show no effect on human normal BJ fibroblast cells. For the first time, the genes with increased expression have been identified and the proteins have been activated by the fatty acid mixture of CLA-enriched egg yolk, mainly responsible for mitochondrial pathway-dependent apoptosis.     

Cadmium-induced oxidative cellular damage in human fetal lung fibroblasts (MRC-5 cells).

Epidemiological evidence suggests that cadmium (Cd) exposure causes pulmonary damage such as emphysema and lung cancer. However, relatively little is known about the mechanisms involved in Cd pulmonary toxicity. In the present study, the effects of Cd exposure on human fetal lung fibroblasts (MRC-5 cells) were evaluated by determination of lipid peroxidation, intra-cellular production of reactive oxygen species (ROS), and changes of mitochondrial membrane potential. A time- and dose-dependent increase of both lactate dehydrogenase leakage and malondialdehyde formation was observed in Cd-treated cells. A close correlation between these two events suggests that lipid peroxidation may be one of the main pathways causing its cytotoxicity. It was also noted that Cd-induced cell injury and lipid peroxidation were inhibited by catalase and superoxide dismutase, two antioxidant enzymes. By using the fluorescent probe 2',7'-dichlorofluorescin diacetate, a significant increase of ROS production in Cd-treated MRC-5 cells was detected. The inhibition of dichlorofluorescein fluorescence by catalase, not superoxide dismutase, suggests that hydrogen peroxide is the main ROS involved. Moreover, the significant dose-dependent changes of mitochondrial membrane potential in Cd-treated MRC-5 cells, demonstrated by increased fluorescence of rhodamine 123 examined using a laser-scanning confocal microscope, also indicate the involvement of mitochondrial damage in Cd cytotoxicity. These findings provide in vitro evidence that Cd causes oxidative cellular damage in human fetal lung fibroblasts, which may be closely associated with the pulmonary toxicity of Cd.     

Conjugated linoleic acid alters caveolae phospholipid fatty acid composition and decreases caveolin-1 expression in MCF-7 breast cancer cells

Conjugated linoleic acid (CLA) refers to a group of biologically active fatty acids that exhibit anticarcinogenic properties; however, the mechanism of action remains poorly understood. Caveolae are specialized plasma membrane structures that affect many facets of cancer cell function, including growth, cell signaling, and apoptosis. Therefore, one potential mechanism could be alteration of caveolae lipid composition and function. We hypothesized that CLA can alter the lipid microenvironment of caveolae and alter expression of the major caveolae-resident protein, caveolin-1. MCF-7 human breast cancer cells were treated with a vehicle control, linoleic acid (LA), or CLA for 3 days after which total cell lysate, plasma membrane, and caveolae membrane fractions were isolated. Our findings indicate that CLA readily incorporates into caveolae (Δ9cis,11trans-18:2 being the major isomer) and maybe preferentially enriched in specific phospholipid species. Furthermore, caveolin-1 localization to caveolae after treatment with CLA was decreased relative to either control- or LA-treated cells, without changes in total cellular levels of protein relative to vehicle-control treated cells. Taken together, our results suggest that further investigation of a potential therapeutic role for CLA in modulating caveolae function in breast cancer is merited.