Ginkgo Biloba Extract Can Antagonize Subchronic Arsenite Exposure-Induced Hepatocyte Senescence by Inhibiting Oxidative Damage and Inflammation in Rats
Ginkgo Biloba Extract Can Antagonize Subchronic Arsenite Exposure-Induced Hepatocyte Senescence by Inhibiting Oxidative Damage and Inflammation in Rats
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DOI：
10.1007/s12011-023-04021-3
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发表时间：
2023-12-19
影响因子：
3.9
通讯作者：
Zhang，Aihua
中科院分区：
文献类型：
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作者：
Chen，Xiong;Wu，Fan;Zhang，Aihua
越来越多的证据表明，长期接触砷会导致肝损伤。我们前期的研究表明，砷中毒患者和砷暴露大鼠会出现肝损伤。但治疗靶点尚不明确，缺乏有效药物。本研究旨在探讨亚砷酸钠（亚砷酸盐）暴露对大鼠肝细胞衰老的影响以及银杏叶提取物的干预作用。在这项研究中，24 只雄性 Sprague–Dawley 大鼠（体重 180-200 克）被随机分为三组。对照组正常饮食，砷暴露组在正常饮食的基础上自由饮酒，给予10mg/L亚砷酸钠，连续3个月。银杏叶提取物治疗组在接触亚砷酸盐 2 个月后连续给予 EGb761（10 mg/kg，灌胃）1 个月。我们的结果表明，与正常对照组相比，暴露于 10 mg/L 亚砷酸盐会导致大鼠肝组织中肝窦间隙变窄、肝细胞增大、多核肝细胞和炎症细胞浸润增加。此外，10 mg/L亚砷酸盐还引起炎症相关指标（IL1-β、IL-6、TNF-α）、氧化损伤相关指标（SOD、MDA、GPx）和衰老相关蛋白（p16、p-p53、E2F1）的异常表达。 EGb761能有效减轻肝组织病理损伤，拮抗亚砷酸盐暴露引起的肝组织炎症、氧化损伤相关指标以及细胞衰老相关蛋白的异常表达。值得注意的是，EGb761 减少了大鼠肝组织中砷的积累。这些结果表明EGb761可以有效缓解亚慢性砷暴露引起的肝细胞衰老，这可能部分是通过抑制大鼠炎症和氧化损伤来实现的。该研究可能为砷引起的肝损伤提供新的治疗靶点。
A growing body of evidence suggests that long-term arsenic exposure can induce liver injury. Our previous studies have demonstrated that liver injury occurs in arsenic-poisoning patients and arsenic-exposed rats. However, therapeutic targets are still unclear, and there is a lack of effective drugs. This study aimed to investigate the effects of sodium arsenite (arsenite) exposure on hepatocyte senescence and the intervention effect of ginkgo biloba extract in rats. In this study, 24 male Sprague–Dawley rats (weighing 180–200 g) were randomized into three groups. The control group received a normal diet, and the arsenic-exposed group was given 10 mg/L arsenite for 3 months by free drinking along with a normal diet. The ginkgo biloba extract treatment group was consecutively administered EGb761 (10 mg/kg, by gavage) for 1 month following 2 months of arsenite exposure. Our results showed that exposure to 10 mg/L arsenite induced narrowing of the hepatic sinus space, enlargement of hepatocytes, and increased multinucleated hepatocytes and inflammatory cell infiltration in rat liver tissue compared with the normal control group. Moreover, 10 mg/L arsenite also caused abnormal expression of inflammation-related indices (IL1-β, IL-6, TNF-α), oxidative damage-related indices (SOD, MDA, GPx), and senescence-related proteins (p16, p-p53, E2F1). EGb761 could effectively reduce the pathological damage of liver tissue and antagonize the abnormal expression of liver tissue inflammation and oxidative damage-related indices as well as cellular senescence-related proteins caused by arsenite exposure. Notably, EGb761 reduced the accumulation of arsenic in rat liver tissues. These results suggested that EGb761 could effectively alleviate subchronic arsenic exposure-induced senescence of hepatocytes, which may be achieved partially through inhibiting inflammation and oxidative damage in rats. This study may provide a new therapeutic target for arsenic-induced liver injury.