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生育三烯酚比生育酚能更好地保护大鼠骨骼免受自由基诱导的损伤。

Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone.

作者信息

Ahmad N S, Khalid B A K, Luke D A, Ima Nirwana S

机构信息

Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia.

出版信息

Clin Exp Pharmacol Physiol. 2005 Sep;32(9):761-70. doi: 10.1111/j.1440-1681.2005.04264.x.

Abstract
  1. Free radicals generated by ferric nitrilotriacetate (FeNTA) can activate osteoclastic activity and this is associated with elevation of the bone resorbing cytokines interleukin (IL)-1 and IL-6. In the present study, we investigated the effects of 2 mg/kg FeNTA (2 mg iron/kg) on the levels of serum IL-1 and IL-6 with or without supplementation with a palm oil tocotrienol mixture or alpha-tocopherol acetate in Wistar rats. 2. The FeNTA was found to elevate levels of IL-1 and IL-6. Only the palm oil tocotrienol mixture at doses of 60 and 100 mg/kg was able to prevent FeNTA-induced increases in IL-1 (P < 0.01). Both the palm oil tocotrienol mixture and alpha-tocopherol acetate, at doses of 30, 60 and 100 mg/kg, were able to reduce FeNTA-induced increases in IL-6 (P < 0.05). Therefore, the palm oil tocotrienol mixture was better than pure alpha-tocopherol acetate in protecting bone against FeNTA (free radical)-induced elevation of bone-resorbing cytokines. 3. Supplementation with the palm oil tocotrienol mixture or alpha-tocopherol acetate at 100 mg/kg restored the reduction in serum osteocalcin levels due to ageing, as seen in the saline (control) group (P < 0.05). All doses of the palm oil tocotrienol mixture decreased urine deoxypyridinoline cross-link (DPD) significantly compared with the control group, whereas a trend for decreased urine DPD was only seen for doses of 60 mg/kg onwards of alpha-tocopherol acetate (P < 0.05). 4. Bone histomorphometric analyses have shown that FeNTA injections significantly lowered mean osteoblast number (P < 0.001) and the bone formation rate (P < 0.001), but raised osteoclast number (P < 0.05) and the ratio of eroded surface/bone surface (P < 0.001) compared with the saline (control) group. Supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent all these FeNTA-induced changes, but a similar dose of alpha-tocopherol acetate was found to be effective only for mean osteoclast number. Injections of FeNTA were also shown to reduce trabecular bone volume (P < 0.001) and trabecular thickness (P < 0.05), whereas only supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent these FeNTA-induced changes.
摘要
  1. 次氮基三乙酸铁(FeNTA)产生的自由基可激活破骨细胞活性,这与骨吸收细胞因子白细胞介素(IL)-1和IL-6水平升高有关。在本研究中,我们在Wistar大鼠中研究了2mg/kg FeNTA(2mg铁/kg)对血清IL-1和IL-6水平的影响,无论是否补充棕榈油生育三烯酚混合物或α-生育酚醋酸酯。

  2. 发现FeNTA可提高IL-1和IL-6水平。仅60和100mg/kg剂量的棕榈油生育三烯酚混合物能够预防FeNTA诱导的IL-1升高(P<0.01)。30、60和100mg/kg剂量的棕榈油生育三烯酚混合物和α-生育酚醋酸酯均能够降低FeNTA诱导的IL-6升高(P<0.05)。因此,在保护骨骼免受FeNTA(自由基)诱导的骨吸收细胞因子升高方面,棕榈油生育三烯酚混合物优于纯α-生育酚醋酸酯。

  3. 补充100mg/kg的棕榈油生育三烯酚混合物或α-生育酚醋酸酯可恢复因衰老导致的血清骨钙素水平降低,如在生理盐水(对照)组中所见(P<0.05)。与对照组相比,所有剂量的棕榈油生育三烯酚混合物均显著降低尿脱氧吡啶啉交联(DPD),而仅60mg/kg及以上剂量的α-生育酚醋酸酯才有降低尿DPD的趋势(P<0.05)。

  4. 骨组织形态计量学分析表明,与生理盐水(对照)组相比,注射FeNTA显著降低平均成骨细胞数量(P<0.001)和骨形成率(P<0.001),但增加破骨细胞数量(P<0.05)和侵蚀表面/骨表面比值(P<0.001)。补充100mg/kg棕榈油生育三烯酚混合物能够预防所有这些FeNTA诱导的变化,但发现相似剂量的α-生育酚醋酸酯仅对平均破骨细胞数量有效。注射FeNTA还显示可减少小梁骨体积(P<0.001)和小梁厚度(P<0.05),而仅补充100mg/kg棕榈油生育三烯酚混合物能够预防这些FeNTA诱导的变化。

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