Background
Docosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid with activities in both infants and adults [1]. Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling [2].
Docosahexaenoic acid (10-30 μM 48 h) treatment induced apoptosis in three colon cancer cell lines (HT-29, HCT116 and SW480), and inhibited their total and surface GRP78 expression. The cell ability to undergo DHA-induced apoptosis was inversely related to their level of GRP78 expression [3]. Doxorubicin chemosensitization of breast cancer cell lines by docosahexaenoic acid was cell-line selective, affecting MDA-MB-231 and MCF-7dox (a doxorubicin-resistant cell line) but not the parental MCF-7 cell line [4].
Intravenous perioperative treatment with DHA (500 μg), resolvin D1 (RvD1, 500 ng) and maresin 1 (MaR1, 500 ng), 10 min and 24 h after the surgery, delayed the development of fPOP (mechanical allodynia and cold allodynia) in a mouse model of post-operative pain induced by tibial bone fracture [5]. Oral administration of DHA to normal adult mice as lysophosphatidylcholine (LPC) (40 mg DHA/kg) for 30 days increased DHA content of the brain by >2-fold. In contrast, the same amount of free DHA did not increase brain DHA, but increased the DHA in adipose tissue and heart [6]. Supplementation of the high-fat diet with either EPA, DPA or DHA prevented the fatty liver, prevented high serum cholesterol and serum glucose and prevented high liver cholesterol levels [7].
参考文献:
[1]. Lien E L. Toxicology and safety of DHA[J]. Prostaglandins, leukotrienes and essential fatty acids, 2009, 81(2-3): 125-132.
[2]. Lauritzen L, Brambilla P, Mazzocchi A, et al. DHA effects in brain development and function[J]. Nutrients, 2016, 8(1): 6.
[3]. Fasano E, Serini S, Piccioni E, et al. DHA induces apoptosis by altering the expression and cellular location of GRP78 in colon cancer cell lines[J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2012, 1822(11): 1762-1772.
[4]. Maheo K, Vibet S, Steghens J P, et al. Differential sensitization of cancer cells to doxorubicin by DHA: a role for lipoperoxidation[J]. Free Radical Biology and Medicine, 2005, 39(6): 742-751.
[5]. Zhang L, Terrando N, Xu Z Z, et al. Distinct analgesic actions of DHA and DHA-derived specialized pro-resolving mediators on post-operative pain after bone fracture in mice[J]. Frontiers in pharmacology, 2018, 9: 412.
[6]. Sugasini D, Thomas R, Yalagala P C R, et al. Dietary docosahexaenoic acid (DHA) as lysophosphatidylcholine, but not as free acid, enriches brain DHA and improves memory in adult mice[J]. Scientific Reports, 2017, 7(1): 1-11.
[7]. Guo X, Sinclair A J, Kaur G, et al. Differential effects of EPA, DPA and DHA on cardio-metabolic risk factors in high-fat diet fed mice[J]. Prostaglandins, Leukotrienes and Essential Fatty Acids, 2018, 136: 47-55.
二十二碳六烯酸 (DHA) 是一种长链多不饱和脂肪酸，对婴儿和成人均有活性[1]。二十二碳六烯酸 (DHA) 是膜的结构成分，特别是在中枢神经系统中。来自细胞和动物研究的数据证明，DHA 与神经元细胞生长和分化的大脑功能以及神经元信号转导有关 [2]。
二十二碳六烯酸（10-30 μM，48 小时）处理可诱导三种结肠癌细胞系（HT-29、HCT116 和 SW480）发生细胞凋亡，并抑制它们的总 GRP78 表达和表面 GRP78 表达。细胞经历 DHA 诱导的细胞凋亡的能力与其 GRP78 表达水平呈负相关[3]。二十二碳六烯酸对乳腺癌细胞系的多柔比星化学增敏具有细胞系选择性，影响 MDA-MB-231 和 MCF-7dox（多柔比星耐药细胞系），但不影响亲代 MCF-7 细胞系 [4]< /sup>.
在手术后 10 分钟和 24 小时使用 DHA（500 μg）、resolvin D1（RvD1，500 ng）和 maresin 1（MaR1，500 ng）进行围手术期静脉内治疗，延缓了 fPOP（机械异常性疼痛和寒冷）的发展异常性疼痛）在胫骨骨折术后疼痛小鼠模型中的作用[5]。给正常成年小鼠口服 DHA 作为溶血磷脂酰胆碱 (LPC) (40 mg DHA/kg) 30 天后，大脑中的 DHA 含量增加了 >2 倍。相比之下，等量的游离 DHA 并没有增加大脑中的 DHA，而是增加了脂肪组织和心脏中的 DHA [6]。在高脂肪饮食中补充 EPA、DPA 或 DHA 可预防脂肪肝，预防高血清胆固醇和高血糖，并预防高肝胆固醇水平[7]。
Protocol
| Cell experiment [1]: |
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Cell lines
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HT-29, HCT116 and SW480 colon cancer cells
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Preparation Method
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HT-29, HCT116 and SW480 colon cancer cells were exposed to Docosahexaenoic acid (DHA) (10-30 μM) for 48 h, and apoptosis was morphologically evaluated after acridine-orange staining.
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Reaction Conditions
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10-30 μM for 48 hours
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Applications
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A much larger fraction of SW480 cells (about 60% with 30 μM DHA) underwent DHA-induced apoptosis than the HCT116 or HT-29 cells (about 15-18% with 30 μM DHA), and that was related to the greater basal propensity for apoptosis of the SW480 cells.
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| Animal experiment [2]: |
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Animal models
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Adult CD1 mice (male, 25-35 g)
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Preparation Method
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Muscles were disassociated following an incision on the left hind paw. A 0.38-mm stainless steel pin was inserted into the tibia intramedullary canal, followed by the osteotomy. The incision was sutured with 6-0 Prolene. For perioperative treatment, Docosahexaenoic acid (500 μg, 100 μl) or SPMs (500 ng, 100 μl) were dissolved in 2% ethanol as vehicle and administered intravenously through tail vein injection at 10 min and 24 h after surgery.
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Dosage form
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500 μg, 100 μl, iv.
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Applications
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Intravenous injections of DHA (500 μg, 100 μl) significantly attenuated mechanical allodynia by decreasing paw withdrawal frequency. Compared to vehicle control, cold allodynia was not significantly reduced by DHA. Cold allodynia in the treatment group was also not significantly different from sham surgery, suggesting a possible inhibition of cold allodynia by the DHA pre-treatment.
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参考文献:
[1] : Fasano E, Serini S, Piccioni E, et al. DHA induces apoptosis by altering the expression and cellular location of GRP78 in colon cancer cell lines[J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2012, 1822(11): 1762-1772.
[2] : Zhang L, Terrando N, Xu Z Z, et al. Distinct analgesic actions of DHA and DHA-derived specialized pro-resolving mediators on post-operative pain after bone fracture in mice[J]. Frontiers in pharmacology, 2018, 9: 412.
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