Deuterium-Reinforced Polyunsaturated Fatty Acids Prevent Diet-Induced Nonalcoholic Steatohepatitis by Reducing Oxidative Stress.
Deuterium-Reinforced Polyunsaturated Fatty Acids Prevent Diet-Induced Nonalcoholic Steatohepatitis by Reducing Oxidative Stress.
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氘强化多不饱和脂肪酸通过减少氧化应激预防饮食引起的非酒精性脂肪性肝炎
DOI：
10.3390/medicina58060790
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发表时间：
2022-06-12
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影响因子：
--
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中科院分区：
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背景和目的：非酒精性脂肪性肝炎(NASH)的进展与氧化应激有关，氧化应激可通过引发炎症反应而发生。与常规氢化(H-−)多不饱和脂肪酸(H-−)相比，氢强化多不饱和脂肪酸(D-PUFA)更能抵抗ROS引发的脂质过氧化链式反应。本研究旨在探讨D-多不饱和脂肪酸对氧化应激的影响及其对NASH的保护作用。材料和方法：C57BL/6小鼠随机分为3组，分别饲喂普通饲料、蛋氨酸胆碱缺乏(MCD)饲料和添加0.6%D-PUFAs的MCD饲料5周。测定小鼠NASH的表型。在体内和体外检测氧化应激水平。结果：D-PUFAs可抑制叔丁基氢过氧化氢(−)负载肝细胞的ROS生成，提高细胞存活率。同时，D-多不饱和脂肪酸可降低四氢呋喃对RAW 264.7巨噬细胞的氧化应激作用。相应地，D-PUFAs提高了巨噬细胞的活力，减弱了内毒素刺激的促炎细胞因子的表达。在体内，给予D-PUFAs减少了MCD喂养的小鼠的NASH表型。具体地说，D-PUFAs降低了NASH小鼠肝脏转氨酶的活性，并减轻了肝脏的脂肪变性、炎症和纤维化。结论：D-多不饱和脂肪酸可能通过广泛减少氧化应激而成为预防NASH的潜在治疗药物。
Background and Objectives: Oxidative stress is implicated in the progression of nonalcoholic steatohepatitis (NASH) through the triggering of inflammation. Deuterium-reinforced polyunsaturated fatty acids (D-PUFAs) are more resistant to the reactive oxygen species (ROS)−initiated chain reaction of lipid peroxidation than regular hydrogenated (H−) PUFAs. Here, we aimed to investigate the impacts of D-PUFAs on oxidative stress and its protective effect on NASH. Materials and Methods: C57BL/6 mice were randomly divided into three groups and were fed a normal chow diet, a methionine–choline-deficient (MCD) diet, and an MCD with 0.6% D-PUFAs for 5 weeks. The phenotypes of NASH in mice were determined. The levels of oxidative stress were examined both in vivo and in vitro. Results: The treatment with D-PUFAs attenuated the ROS production and enhanced the cell viability in tert-butyl hydroperoxide (TBHP)−loaded hepatocytes. Concurrently, D-PUFAs decreased the TBHP-induced oxidative stress in Raw 264.7 macrophages. Accordingly, D-PUFAs increased the cell viability and attenuated the lipopolysaccharide-stimulated proinflammatory cytokine expression of macrophages. In vivo, the administration of D-PUFAs reduced the phenotypes of NASH in MCD-fed mice. Specifically, D-PUFAs decreased the liver transaminase activity and attenuated the steatosis, inflammation, and fibrosis in the livers of NASH mice. Conclusion: D-PUFAs may be potential therapeutic agents to prevent NASH by broadly reducing oxidative stress.
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影响因子：
15
作者：
Lamberson CR;Xu L;Muchalski H;Montenegro-Burke JR;Shmanai VV;Bekish AV;McLean JA;Clarke CF;Shchepinov MS;Porter NA
通讯作者：
Porter NA
影响因子：
29.4
作者：
Cotter, Thomas G.;Rinella, Mary
通讯作者：
Rinella, Mary
影响因子：
18.2
作者：
Hamidzadeh K;Christensen SM;Dalby E;Chandrasekaran P;Mosser DM
通讯作者：
Mosser DM
影响因子：
11.4
作者：
Cotticelli MG;Crabbe AM;Wilson RB;Shchepinov MS
通讯作者：
Shchepinov MS
影响因子：
4.7
作者：
Angelova PR;Horrocks MH;Klenerman D;Gandhi S;Abramov AY;Shchepinov MS
通讯作者：
Shchepinov MS