Restorative potential of (-)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue.

Restorative potential of (-)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue.
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DOI:
10.1038/s41598-021-01093-w
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发表时间:
2021-11-08
期刊:
影响因子:
4.6
通讯作者:
Villarreal F
Villarreal F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ramirez-Sanchez I;Navarrete-Yañez V;Garate-Carrillo A;Lara-Hernandez M;Espinosa-Raya J;Moreno-Ulloa A;Gomez-Diaz B;Cedeño-Garcidueñas AL;Ceballos G;Villarreal F

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我们在海湾战争病(GWI)大鼠模型中研究了(-)-表儿茶素(Epi)逆转骨骼肌(SkM)萎缩和功能障碍,减少炎症介质和正常化代谢紊乱的潜力。雄性Wistar大鼠(n = 15)经口给予溴化吡啶斯的明(PB)1.3 mg/kg/d、氯菊酯(PM)0.13 mg/kg/d(皮肤)、避蚊胺(DEET)40 mg/kg/d(皮肤),并进行3周的身体约束,每天5 min。随后一周的时间完全形成GWI样特征,随后通过管饲法(n = 8)或水(n = 7)以1 mg/kg/天的Epi处理2周作为对照。正常对照组(n = 15)给予溶剂,不受限制。在6周时,对动物进行跑步机和肢体强度测试,然后实施安乐死。SkM和血液采样用于组织学、生物化学和血浆促炎细胞因子和代谢组学评估。GWI动物出现中毒特征,其特征为SkM萎缩和功能丧失,伴有肌肉萎缩、降解标志物和血浆促炎细胞因子水平的调节剂增加。相对于正常对照,用Epi处理GWI动物产生上述指标的显著部分或完全正常化。血浆代谢组学显示,与炎症和SkM废物途径相关的代谢物在GWI组中失调,而Epi减弱了这种变化。总之,在GWI大鼠模型中,Epi部分逆转了SkM结构的有害变化,包括萎缩、炎症和选择性血浆代谢产物的调节剂,从而改善了功能。
We examined in a rat model of Gulf War illness (GWI), the potential of (−)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicle and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi partially reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.
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