Concentrated fish oil (Lovaza(R)) extends lifespan and attenuates kidney disease in lupus-prone short-lived (NZBxNZW)F1 mice.
Concentrated fish oil (Lovaza(R)) extends lifespan and attenuates kidney disease in lupus-prone short-lived (NZBxNZW)F1 mice.
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DOI：
10.1177/1535370213489485
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发表时间：
2013-06
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;Williams PJ;Veigas JM;Barnes JL;Fernandes G
越来越多的报道表明鱼油（FO）的抗炎作用对系统性红斑狼疮（SLE）有益。然而，大多数临床前研究使用5-20% FO进行，这高于狼疮患者的临床相关剂量。进行本研究是为了确定与常用的FO-18/12（18-二十碳五烯酸[EPA]/12-二十二碳六烯酸[DHA]）相比，FDA批准的浓缩FO（Lovaza®）的有效低剂量。我们检查了Lovaza®（1%和4%）对SLE小鼠品系（NZB×NZW）F1的剂量依赖性反应，并将其与1%和4%安慰剂以及4% FO-18/12进行了比较，以标准食物作为对照。结果首次显示，1% Lovaza®可延长（NZB × NZW）F1小鼠的最大寿命（517 d），4% Lovaza®可显著延长（NZB×NZW）F1小鼠的中位寿命（502 d）和最大寿命（600 d）。相比之下，FO-18/12仅延长中位寿命（410天），而标准饲料（301天）。此外，与安慰剂相比，4% Lovaza®显著降低了抗dsDNA抗体，减轻了肾小球肾炎，并减弱了脾细胞中脂多糖诱导的促炎细胞因子（IL-1β、IL-6、TNF-α）。与安慰剂相比，4% Lovaza®还显示可降低炎性细胞因子（包括IL-1β、IL-6和TNF-α）的表达，同时增加肾脏抗氧化酶。值得注意的是，与安慰剂相比，4% Lovaza®降低了NFκB活化和p65核转位。这些数据表明，1%的Lovaza®是有益的，但4%的Lovaza®在抑制肾小球肾炎和延长SLE易感性短命小鼠的寿命方面更有效，可能是通过减少炎症信号传导和调节氧化应激。
A growing number of reports indicate that anti-inflammatory actions of fish oil (FO) are beneficial against systemic lupus erythematosus (SLE). However, the majority of pre-clinical studies were performed using 5–20% FO, which is higher than the clinically relevant dose for lupus patients. The present study was performed in order to determine the effective low dose of FDA-approved concentrated FO (Lovaza®) compared to the commonly used FO-18/12 (18-Eicosapentaenoic acid [EPA]/12-Docosahexaenoic acid [DHA]). We examined the dose-dependent response of Lovaza® (1% and 4%) on an SLE mouse strain (NZB×NZW)F1 and compared the same with 1% and 4% placebo, as well as 4% FO-18/12, maintaining standard chow as the control. Results show for the first time that 1% Lovaza® extends maximal lifespan (517 d) and 4% Lovaza® significantly extends both the median (502 d) and maximal (600 d) life span of (NZB×NZW)F1 mice. In contrast, FO-18/12 extends only median lifespan (410 d) compared to standard chow diet (301 d). Additionally, 4% Lovaza® significantly decreased anti-dsDNA antibodies, reduced glomerulonephritis and attenuated lipopolysaccharide-induced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in splenocytes compared to placebo. 4% Lovaza® was also shown to reduce the expression of inflammatory cytokines, including IL-1β, IL-6 and TNF-α, while increasing renal anti-oxidant enzymes in comparison to placebo. Notably, NFκB activation and p65 nuclear translocation were lowered by 4% Lovaza® compared to placebo. These data indicate that 1% Lovaza® is beneficial, but 4% Lovaza® is more effective in suppressing glomerulonephritis and extending life span of SLE-prone short-lived mice, possibly via reducing inflammation signaling and modulating oxidative stress.
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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：
3.4
作者：
Aghdassi, Elaheh;Ma, David W. L.;Fortin, Paul R.
通讯作者：
Fortin, Paul R.
影响因子：
6.4
作者：
Kalergis, Alexis M.;Iruretagoyena, Mirentxu I.;Jacobelli, Sergio H.
通讯作者：
Jacobelli, Sergio H.
影响因子：
5.6
作者：
Halade, Ganesh V.;Rahman, Md M.;Williams, Paul J.;Fernandes, Gabriel
通讯作者：
Fernandes, Gabriel
DOI：
10.4049/jimmunol.0903282
发表时间：
2010-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Halade GV;Rahman MM;Bhattacharya A;Barnes JL;Chandrasekar B;Fernandes G
通讯作者：
Fernandes G