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姜黄素载药纳米粒能有效预防 T 诱导的大鼠心脏氧化应激。

Curcumin-loaded nanoparticles effectively prevent T-induced oxidative stress in rat heart.

机构信息

Department of Zoology, SCS Autonomous College, Puri, Odisha, India.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.

出版信息

Cell Biochem Funct. 2024 Jun;42(4):e4070. doi: 10.1002/cbf.4070.

Abstract

In this study, we report the cardioprotective effect of the glycerol monooleate (GMO) based nanocurcumin in both in vitro and in vivo conditions under a hyperthyroid state. The heart is one of the primary target organs sensitive to the action of thyroid hormone, and slight variations in the thyroid hormone serum concentrations result in measurable changes in cardiac performance. Hyperthyroidism-induced hypermetabolism is associated with oxidative stress and is an important mechanism responsible for the progression of heart failure. Curcumin has been known to play a protective role against oxidative stress-related diseases like Alzheimer's, asthma, and aging due to its antioxidant properties. Nevertheless, its potent biological activity has been hindered due to its poor bioavailability. To overcome this drawback, a GMO-based biodegradable nanoparticle (NP) formulation loaded with curcumin has been developed, and the protective effect of curcumin-loaded NPs was compared against the native drug. Oxidative stress parameters like reactive oxygen species (ROS) release, change in mitochondrial membrane permeability, lipid peroxidation (LPx), lactate dehydrogenase (LDH) release, and the activity and protein expression of the endogenous antioxidant enzymes like superoxide dismutase, catalase (CAT) and glutathione peroxidase were evaluated. The results from in vitro showed that curcumin-loaded NPs showed better DPPH and NO radical scavenging activity than native curcumin in a concentrations range of 2.5-20 µM. It was also observed that the nanoparticulate curcumin was comparatively more effective than native curcumin in protecting against ROS-induced membrane damage by reducing LPx and LDH leakage at low concentrations of 5-10 µM. Further, curcumin NPs performed better in facilitating the activities of antioxidant enzymes under in vitro and in vivo conditions with respect to time and concentrations, resulting in reduced cellular ROS levels. In this scenario, we anticipate that curcumin-loaded NPs can serve as a better antioxidant than its native counterpart in protecting the heart from oxidative stress-related diseases.

摘要

在这项研究中,我们报告了甘油单油酸酯(GMO)基纳米姜黄素在甲状腺功能亢进状态下的体外和体内条件下的心脏保护作用。心脏是对甲状腺激素作用敏感的主要靶器官之一,甲状腺激素血清浓度的微小变化导致心脏功能的可测量变化。甲状腺功能亢进引起的高代谢与氧化应激有关,是心力衰竭进展的重要机制。姜黄素由于其抗氧化特性,已被证明在与氧化应激相关的疾病(如阿尔茨海默病、哮喘和衰老)中发挥保护作用。然而,由于其生物利用度差,其强大的生物学活性受到阻碍。为了克服这一缺点,已经开发了一种基于 GMO 的可生物降解纳米颗粒(NP)制剂,其中负载有姜黄素,并比较了负载姜黄素的 NP 与天然药物的保护作用。评估了氧化应激参数,如活性氧(ROS)释放、线粒体膜通透性变化、脂质过氧化(LPx)、乳酸脱氢酶(LDH)释放以及超氧化物歧化酶、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶等内源性抗氧化酶的活性和蛋白表达。体外结果表明,负载姜黄素的 NP 在 2.5-20 μM 的浓度范围内比天然姜黄素具有更好的 DPPH 和 NO 自由基清除活性。还观察到,纳米颗粒姜黄素在较低浓度 5-10 μM 时,通过减少 LPx 和 LDH 漏出,比天然姜黄素更有效地保护 ROS 诱导的膜损伤。此外,负载姜黄素的 NP 在体外和体内条件下,在时间和浓度方面,更有效地促进抗氧化酶的活性,从而降低细胞内 ROS 水平。在这种情况下,我们预计负载姜黄素的 NP 可以作为一种比天然姜黄素更好的抗氧化剂,保护心脏免受与氧化应激相关的疾病。

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