Docosahexaenoic acid-enriched fish oil attenuates kidney disease and prolongs median and maximal life span of autoimmune lupus-prone mice.
Docosahexaenoic acid-enriched fish oil attenuates kidney disease and prolongs median and maximal life span of autoimmune lupus-prone mice.
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DOI：
10.4049/jimmunol.0903282
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发表时间：
2010-05-01
期刊：
影响因子：
--
通讯作者：
Fernandes G
中科院分区：
文献类型：
--
作者：
Halade GV;Rahman MM;Bhattacharya A;Barnes JL;Chandrasekar B;Fernandes G
鱼油（FO）的单个组分在各种人类炎症性疾病中的治疗功效仍然没有得到解决，可能是由于n-3脂肪酸二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）的水平较低或DHA与EPA的比例较低。由于富含DHA（FO-DHA）或EPA（FO-EPA）的FO最近已经上市，我们在一个完善的人类系统性红斑狼疮（SLE）动物模型中研究了它们对生存和炎症性肾脏疾病的疗效。结果首次显示，FO-DHA显著延长了（NZB × NZW）F1（B × W）小鼠的中位寿命（658天）和最长寿命（848天）。相比之下，FO-EPA喂养的小鼠的中位寿命和最大寿命分别为约384天和500天。对可能的生存机制的研究表明，FO-DHA（相对于FO-EPA）降低血清抗dsDNA抗体，肾脏中的IgG沉积和蛋白尿。此外，FO-DHA降低了LPS介导的血清IL-18水平的升高以及肾脏中IL-18前体向成熟IL-18的caspase-1依赖性切割。此外，FO-DHA还能抑制LPS介导的PI 3 K、Akt和NF-κB的激活。这些数据表明，DHA而不是EPA是抑制肾小球肾炎和延长SLE易感短命B × W小鼠寿命的最有效的n-3脂肪酸，可能通过抑制IL-18诱导和IL-18依赖性信号传导。
The therapeutic efficacy of individual components of fish oils (FO) in various human inflammatory diseases still remains unresolved, possibly due to low levels of n-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or lower ratio of DHA to EPA. Since FO enriched with DHA (FO-DHA) or EPA (FO-EPA) has become available recently, we investigated their efficacy on survival and inflammatory kidney disease in a well-established animal model of human Systemic Lupus Erythematosus (SLE). Results show for the first time that FO-DHA dramatically extends both the median (658 days) and maximal (848 days) lifespan of (NZB × NZW)F1 (B × W) mice. In contrast, FO-EPA fed mice had a median and maximal lifespan of ~384 and 500 days, respectively. Investigations into possible survival mechanisms revealed that FO-DHA (Vs. FO-EPA) lowers serum anti-dsDNA antibodies, IgG deposition in kidneys, and proteinuria. Further, FO-DHA lowered LPS-mediated increases in serum IL-18 levels and caspase-1-dependent cleavage of pro-IL-18 to mature IL-18 in kidneys. Moreover, FO-DHA suppressed LPS-mediated PI3K, Akt, and NF-κB activations in kidney. These data indicate that DHA, but not EPA, is the most potent n-3 fatty acid that suppresses glomerulonephritis and extends lifespan of SLE-prone short-lived B × W mice, possibly via inhibition of IL-18 induction and IL-18-dependent signaling.
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影响因子：
82.9
作者：
Barber, DF;Bartolomé, A;Carrera, AC
通讯作者：
Carrera, AC
DOI：
10.1006/bbrc.1994.1534
发表时间：
1994-04-29
影响因子：
3.1
作者：
CHANDRASEKAR, B;FERNANDES, G
通讯作者：
FERNANDES, G
影响因子：
7.1
作者：
Calder, Philip C.
通讯作者：
Calder, Philip C.
DOI：
10.1016/j.bbapap.2007.10.003
发表时间：
2008-01-01
影响因子：
3.2
作者：
Marone, Romina;Cmijanovic, Vladimir;Wymann, Matthias P.
通讯作者：
Wymann, Matthias P.
影响因子：
9.1
作者：
Muthukumar, AR;Jolly, CA;Fernandes, G
通讯作者：
Fernandes, G