Spherical neutral gold nanoparticles improve anti-inflammatory response, oxidative stress and fibrosis in alcohol-methamphetamine-induced liver injury in rats
Spherical neutral gold nanoparticles improve anti-inflammatory response, oxidative stress and fibrosis in alcohol-methamphetamine-induced liver injury in rats
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DOI：
10.1016/j.ijpharm.2018.06.008
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发表时间：
2018-09-01
影响因子：
5.8
通讯作者：
de Araujo Junior, Raimundo Fernandes
中科院分区：
文献类型：
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作者：
de Carvalho, Thais Gomes;Garcia, Vinicius Barreto;de Araujo Junior, Raimundo Fernandes
本研究旨在探讨纳米金(GNPs)对乙醇和甲基苯丙胺所致大鼠肝损伤的抗炎、抗氧化和抗肝纤维化作用。以30%乙醇溶液(7g/kg)灌胃，连续28天1次，然后于第20、28天给予冰毒(10 mg/kg)，造成肝损伤。在酒精和冰毒暴露期间给予GNP(724.96微克/公斤)可减轻脂肪变性、肝索变性、纤维化和坏死。此外，与单纯乙醇+冰毒组相比，肝损伤和氧化应激的生化标记物以及促炎细胞因子IL-1β和TNF-α均降低。成纤维细胞生长因子、超氧化物歧化酶-1和GPX-1的表达也减少。在乙醇+冰毒诱导的大鼠肝损伤模型中，GNP通过调节信号通路AKT/PI3K和MAPK，下调Kupffer细胞和肝星状细胞的活性，影响其促炎细胞因子、氧化应激和纤维化的表达。
This study aimed to elucidate the anti-inflammatory, anti-oxidant and antifibrotic effects of gold nanoparticles (GNPs) in rats subjected to liver injury with ethanol and Methamphetamine (METH). The liver injury was induced by gavage administrations of 30% alcoholic solution (7 g/kg) once a day during 28 days, followed by METH (10 mg/kg) on the 20th and 28th days of treatment. GNPs treatment (724.96 mu g/kg) during the ethanol and METH exposure was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis. Furthermore, there was a reduction in biochemical markers of liver damage and oxidative stress, and proinflammatory cytokines IL-1 beta and TNF-alpha, compared to ethanol + METH group alone. A decrease of FGF, SOD-1 and GPx-1 expression was also observed. GNPs down-regulated the activity of Kupffer cells and hepatic stellate cells affecting the profile of their pro-inflammatory cytokines, oxidative stress and fibrosis through modulation of signaling pathways AKT/PI3K and MAPK in ethanol+ METH-induced liver injury in a rat model.