Suppression of acetaminophen-induced hepatocyte ultrastructural alterations in rats using a combination of resveratrol and quercetin
Suppression of acetaminophen-induced hepatocyte ultrastructural alterations in rats using a combination of resveratrol and quercetin
复制标题
DOI：
10.1080/01913123.2019.1680585
复制
发表时间：
2019-10-20
影响因子：
1
通讯作者：
Haidara, Mohamed A.
中科院分区：
文献类型：
--
作者：
Al Humayed, Suliman;Al-Ani, Bahjat;Haidara, Mohamed A.
摄入有毒剂量的止痛药对乙酰氨基酚（也称为扑热息痛或APAP）是人类急性肝损伤的最常见原因之一。我们测试了这一假设，即组合多酚化合物，白藜芦醇（RES）和槲皮素（QUR），可以实质上保护肝细胞超微结构损伤诱导的毒性剂量的APAP在大鼠模型中的APAP诱导的急性肝损伤。模型组大鼠单次给予APAP（2g/kg），保护组大鼠在单次给予APAP前给予RES（30 mg/kg）和QUR（50 mg/kg）联合预处理7 d。然后在摄入APAP后24小时处死所有大鼠。制备收获的肝组织用于透射电子显微镜（TEM）染色，并测定肝匀浆中炎症生物标志物，如肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6），以及氧化应激，如丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）。此外，还对血液样本进行了肝损伤酶丙氨酸氨基转移酶（ALT）检测，作为肝损伤的指标。TEM图像显示，APAP过量诱导急性肝损伤，表现为深刻的肝细胞超微结构改变，RES+QUR基本上保护。此外，APAP显著（p < 0.05）调节TNF-β，IL-6、MDA、SOD、GPx和ALT生物标志物，其被RES+QUR完全保护。因此，RES+QUR有效地保护大鼠免受APAP诱导的急性肝损伤，可能是通过抑制炎症和氧化应激。
Ingestion of a toxic dose of the analgesic drug, acetaminophen (also called paracetamol or APAP), is among the most common causes of acute liver injury in humans. We tested the hypothesis that the combined polyphenolic compounds, resveratrol (RES) and quercetin (QUR), can substantially protect against hepatocyte ultrastructural damage induced by a toxic dose of APAP in a rat model of APAP-induced acute liver injury. The model group of rats received a single dose of APAP (2 g/kg), whereas the protective group of rats was pretreated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP. All rats were then sacrificed 24 hours post APAP ingestion. Harvested liver tissues were prepared for transmission electron microscopy (TEM) staining, and liver homogenates were assayed for biomarkers of inflammation, such as tumor necrosis factor-alpha (TNF-?) and interleukin-6 (IL-6), and oxidative stress, such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx). In addition, blood samples were assayed for the liver injury enzyme alanine aminotransferase (ALT) as an indicator of liver damage. TEM images showed that APAP overdose induced acute liver injury as demonstrated by profound hepatocyte ultrastructural alterations, which were substantially protected by RES+QUR. In addition, APAP significantly (p < 0.05) modulated TNF-?, IL-6, MDA, SOD, GPx, and ALT biomarkers, which were completely protected by RES+QUR. Thus, RES+QUR effectively protects against APAP-induced acute liver injury in rats, possibly via the inhibition of inflammation and oxidative stress.