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Betaine alleviates cholestasis-associated renal injury by mitigating oxidative stress and enhancing mitochondrial function
Biologia ( IF 1.4 ) Pub Date : 2020-08-17 , DOI: 10.2478/s11756-020-00576-x
Mohammad Mehdi Ommati , Omid Farshad , Negar Azarpira , Marzieh Shafaghat , Hossein Niknahad , Reza Heidari

Cholestasis-associated renal injury, known as cholemic nephropathy (CN), is a severe clinical complication. CN could lead to acute kidney injury. However, there is no specific pharmacological intervention for cholestasis-induced renal injury. Oxidative stress and mitochondrial impairment seem to play a role in the pathogenesis of CN. Betaine (3-methyl glycine; BET) is an amino acid derivative with a wide range of pharmacological actions. Several studies mentioned the effects of BET on oxidative stress in different experimental models. It has also been found that BET positively affected mitochondrial function. The current study aimed to evaluate the effects of BET supplementation on CN in the bile duct ligation (BDL) model of cholestasis. BET (0.25% and 1% w: v in drinking water) was administered to BDL animals for seven consecutive days. Biomarkers of oxidative stress and mitochondrial indices were evaluated in cholestatic animals. Significant elevation in reactive oxygen species formation, lipid peroxidation, and oxidized glutathione (GSSG) was evident in BDL rats. Moreover, reduced glutathione (GSH) levels and renal antioxidant capacity were decreased in cholestatic animals. Mitochondrial depolarization, mitochondrial permeabilization, decreased mitochondrial dehydrogenases activity, and lipid peroxidation was also detected in the kidney of BDL rats. Tubular atrophy, interstitial inflammation, and renal fibrosis were also detected in BDL rats. BET alleviated biomarkers of oxidative stress, improved mitochondrial indices, and decreased renal histopathological alterations in BDL animals. The antioxidant effects and the positive effects of BET on cellular mitochondria seem to play a fundamental role in its nephroprotective role during cholestasis.



中文翻译:

甜菜碱通过减轻氧化应激和增强线粒体功能减轻胆汁淤积相关的肾脏损伤

与胆汁淤积相关的肾脏损伤,称为胆汁性肾病(CN),是一种严重的临床并发症。CN可能导致急性肾损伤。但是,尚无针对胆汁淤积性肾损伤的特异性药理干预措施。氧化应激和线粒体损伤似乎在CN的发病机理中起作用。甜菜碱(3-甲基甘氨酸; BET)是一种具有广泛药理作用的氨基酸衍生物。几项研究提到了BET对不同实验模型中氧化应激的影响。还已经发现,BET积极影响线粒体功能。当前的研究旨在评估胆汁淤积的胆管结扎(BDL)模型中补充BET对CN的影响。连续7天向BDL动物给药BET(饮用水中0.25%和1%w:v)。在胆汁淤积动物中评估了氧化应激和线粒体指数的生物标记。在BDL大鼠中,活性氧形成,脂质过氧化和氧化型谷胱甘肽(GSSG)明显升高。此外,胆汁淤积动物体内降低的谷胱甘肽(GSH)水平和肾脏抗氧化能力降低。在BDL大鼠的肾脏中也检测到线粒体去极化,线粒体通透性,线粒体脱氢酶活性降低和脂质过氧化。在BDL大鼠中也检测到了肾小管萎缩,间质性炎症和肾纤维化。BET减轻了BDL动物的氧化应激生物标志物,改善了线粒体指数并减少了肾脏组织病理学改变。

更新日期:2020-08-17
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