Elbe Hulya, Gul Mehmet, Cetin Asli, Taslidere Elif, Ozyalin Fatma, Turkoz Yusuf, Otlu Ali
a Faculty of Medicine, Department of Histology and Embryology , Mugla Sıtkı Kocman University , Mugla , Turkey.
b Faculty of Medicine, Department of Histology and Embryology , Inonu University , Malatya , Turkey.
Ultrastruct Pathol. 2018 Jan-Feb;42(1):39-48. doi: 10.1080/01913123.2017.1374313. Epub 2017 Dec 1.
Hepatotoxicity is a major complication of acetaminophen (APAP), a widely used analgesic and antipyretic drug. Resveratrol (RSV) is a naturally occurring diphenol and it has anticancer, antioxidant, and anti-inflammatory properties.
In this study, the beneficial effects of RSV on APAP-induced hepatotoxicity was investigated in rats.
Group 1: Ethanol, Group 2: Saline, Group 3: RSV (10 mg/kg/ip), Group 4: APAP (1000 mg/kg/ip/single dose), Group 5: APAP+RSV (20 min after administration of APAP). The rats were sacrificed 24 h after administration of APAP. Light and electron microscopic changes were evaluated. Levels of malondialdehyde (MDA) and glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities were determined in liver tissue.
Rats of the ethanol, saline, and RSV groups did not present any histopathological alterations. In the APAP group, we observed vascular congestion, necrosis, inflammation, sinusoidal dilatation, and loss of glycogen content. In the APAP+RSV group, these changes were markedly reduced. iNOS immunostaining showed very weak positive stained hepatocytes the sections of control, saline, and RSV groups. However, in the APAP group, iNOS immunostaining was most evident in pericentral hepatocytes. In the same areas in APAP+RSV group, intensity of iNOS immunostaining decreased. A significant increase in MDA and decreases in GSH level, CAT, and SOD activity indicated that APAP-induced hepatotoxicity was mediated through oxidative stress. Significant beneficial changes were noted in tissue oxidative stress indicators in rats treated with RSV.
These biochemical, histopathological, and ultrastructural findings revealed that RSV reduced the severity of APAP-induced alterations in liver.
肝毒性是对乙酰氨基酚（APAP）的主要并发症，APAP是一种广泛使用的解热镇痛药。白藜芦醇（RSV）是一种天然存在的双酚，具有抗癌、抗氧化和抗炎特性。
本研究在大鼠中探究了RSV对APAP诱导的肝毒性的有益作用。
第1组：乙醇；第2组：生理盐水；第3组：RSV（10毫克/千克/腹腔注射）；第4组：APAP（1000毫克/千克/腹腔注射/单剂量）；第5组：APAP+RSV（APAP给药后20分钟）。在APAP给药24小时后处死大鼠。评估光镜和电镜下的变化。测定肝组织中丙二醛（MDA）、谷胱甘肽（GSH）水平、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活性。
乙醇组、生理盐水组和RSV组大鼠未出现任何组织病理学改变。在APAP组中，我们观察到血管充血、坏死、炎症、肝血窦扩张和糖原含量减少。在APAP+RSV组中，这些变化明显减轻。诱导型一氧化氮合酶（iNOS）免疫染色显示，对照组、生理盐水组和RSV组切片中肝细胞的阳性染色非常弱。然而，在APAP组中，iNOS免疫染色在中央周围肝细胞中最为明显。在APAP+RSV组的相同区域，iNOS免疫染色强度降低。MDA显著增加，GSH水平、CAT和SOD活性降低，表明APAP诱导的肝毒性是通过氧化应激介导的。在用RSV治疗的大鼠中，组织氧化应激指标有显著的有益变化。
这些生化、组织病理学和超微结构结果表明，RSV减轻了APAP诱导的肝脏改变的严重程度。
