Hesperidin, a citrus flavonoid, protects against l-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats.

Hesperidin, a citrus flavonoid, protects against l-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats.
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DOI:
10.1080/13880209.2016.1231695
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发表时间:
2017-12
影响因子:
3.8
通讯作者:
Diwan PV
Diwan PV
中科院分区:
医学3区
文献类型:
--
作者:
Hemanth Kumar B;Dinesh Kumar B;Diwan PV

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橙皮苷(HSP)是一种在柑橘类水果中发现的黄烷糖苷配基,具有抗氧化、抗炎和神经保护作用。目的:探讨热休克蛋白(HSP)对L-蛋氨酸诱导的大鼠高同型半胱氨酸血症(HHcy)的保护作用。材料与方法:雄性Wistar大鼠随机分为DMSO、L-蛋氨酸、HSP(25、50和100 mg/kg)、HSP本身(100 mg/kg)和多奈哌齐(0.1 mg/kg)7组。通过口服l-蛋氨酸(1.7g/kg)32天诱导HHcy。从研究的第14天开始,HSP(25、50和100 mg/kg)和多奈哌齐经口给予L-甲硫氨酸处理的大鼠。采用Morris水迷宫(MWM)和视频跟踪Y-迷宫检测HHcy所致大鼠认知功能障碍(28 ~ 32天)。评估血清和脑中HHcy的不同生物标志物和血管反应性,并进行组织病理学(胸主动脉和脑)。结果如下:HSP(100 mg/kg)治疗的L-蛋氨酸处理大鼠表现出显着的(p < 0.001)剂量依赖性活动和减少行为缺陷,脑乙酰胆碱酯酶(25.99 ± 2.36对10.73 ± 1.26 μ mol/mg),脑脂质过氧化(15.25 ± 1.65 vs 6.18 ± 0.74 nM/mg)、血清同型半胱氨酸(Hcy)(22.37 ± 0.30 vs 11.01 ± 1.01 μg/mL)和血清胆固醇(182.7 ± 2.15 vs 101.5 ± 2.76 mg/dL)以及脑抗氧化剂水平升高。HSP通过消除L-蛋氨酸对乙酰胆碱诱导的内皮依赖性舒张的作用显著(p < 0.001)降低内皮功能障碍(艾德),并增加血清亚硝酸盐和血管一氧化氮的生物利用度,沿着组织学畸变的恢复。结论:HSP通过减轻氧化应激、艾德和神经毒性对HHcy具有保护作用。
Context: Hesperidin (HSP), a flavanoglycone found in citrus fruits, has antioxidant, anti-inflammatory and neuroprotective properties. Objective: This study evaluates the protective effect of HSP on l-methionine-induced hyperhomocysteinemia (HHcy) in rats. Materials and methods: Male Wistar rats were randomly divided into seven groups as DMSO, l-methionine, HSP (25, 50 and 100 mg/kg), HSP-per se (100 mg/kg) and donepezil (0.1 mg/kg). HHcy was induced by oral administration of l-methionine (1.7 g/kg) for 32 days. From the 14th day of study HSP (25, 50 and 100 mg/kg) and donepezil was administered orally to l-methionine-treated rats. Cognitive impairment induced by HHcy was determined using the Morris water maze (MWM) and Y-maze on video tracking system (28th–32nd day). Different biomarkers of HHcy in serum and brain and vascular reactivity were evaluated and histopathology (thoracic aorta and brain) was done. Results: HSP (100 mg/kg) treatment in l-methionine-treated rats exhibited significant (p < 0.001) dose-dependent activity and reduced behavioural deficits, brain acetylcholinesterase (25.99 ± 2.36 versus 10.73 ± 1.26 μmoles/mg), brain lipid peroxidation (15.25 ± 1.65 versus 6.18 ± 0.74 nM/mg), serum homocysteine (Hcy) (22.37 ± 0.30 versus 11.01 ± 1.01 μg/mL) and serum cholesterol (182.7 ± 2.15 versus 101.5 ± 2.76 mg/dL) and increased brain antioxidant levels. HSP significantly (p < 0.001) reduced endothelial dysfunction (ED) by abolishing the effect of l-methionine on acetylcholine-induced endothelial-dependent relaxation and increased serum nitrite and vascular nitric oxide bioavailability along with the restoration of histological aberrations. Conclusion: HSP exerts a protective effect on HHcy by abrogating oxidative stress, ED and neurotoxicity.
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