Ciftel Sedat, Cicek Betul, Bolat Ismail, Bulut Seval, Yildirim Serkan, Suleyman Bahadir, Qaniyev Musa, Süleyman Halis
Division of Gastroenterology, Erzurum City Hospital, Erzurum, 25240, Turkey.
Department of Physiology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, 24100, Turkey.
Sci Rep. 2025 Aug 26;15(1):31331. doi: 10.1038/s41598-025-17356-9.
The objective of this study was to elucidate the impact of D-(-)-Quinic acid (D-(-)-QA), a natural phenolic acid, on the molecular mechanisms of inflammation and oxidative stress in brain and liver damage in thioacetamide (TAA)-induced hepatic encephalopathy (HE) in rats. To establish an experimental HE model, rats were injected with three doses (200 mg/kg, intraperitoneally) of TAA every other day, followed by the administration of D-(-)- QA (200 or 400 mg/kg, orally) for fourteen days. Serum ammonia, alanine transaminase (ALT), and aspartate transaminase (AST) levels were detected. Tumor necrosis factor (TNF-α), interleukin-1beta IL-1β, and malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were analyzed to assess inflammation and oxidative damage in brain and liver tissues. Histopathological examinations, immunofluorescence (PI3K and AKT expressions), and immunohistochemical (HSP70 expression) examinations were also performed. TAA administration causedhyperammonemia and increased ALT and AST levels, along with histopathological changes indicating damage to hepatocytes and neurons. Additionally, it disrupted the inflammatory response and promoted oxidative damage by activating the PI3K/AKT-related HSP70 response in the brain and liver. Treatment with D-(-)-QA significantly prevented the increase in ammonia levels and improved the liver function. In addition, the increase in TNF-α, and IL-1β, proinflammatory cytokines in liver and brain tissues as well as the increase in MDA and decrease in SOD and GSH were significantly suppressed by D-(-)-QA. By suppressing HSP70 and PI3K/AKT signaling in brain and liver tissues, D-(-)-QA administration attenuated inflammation and oxidative damage. D-(-)-QA may be an alternative to current clinical interventions by inhibiting inflammation and oxidative damage signaling toward the pathogenesis of HE.
本研究的目的是阐明天然酚酸D -（-）-奎尼酸（D -（-）-QA）对硫代乙酰胺（TAA）诱导的大鼠肝性脑病（HE）中脑和肝损伤的炎症及氧化应激分子机制的影响。为建立实验性HE模型，每隔一天给大鼠腹腔注射三剂（200 mg/kg）TAA，随后口服给予D -（-）-QA（200或400 mg/kg），持续十四天。检测血清氨、丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平。分析肿瘤坏死因子（TNF-α）、白细胞介素-1β（IL-1β）以及丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽（GSH）水平，以评估脑和肝组织中的炎症及氧化损伤。还进行了组织病理学检查、免疫荧光（PI3K和AKT表达）以及免疫组织化学（HSP70表达）检查。给予TAA导致高氨血症，ALT和AST水平升高，同时伴有肝细胞和神经元损伤的组织病理学变化。此外，它通过激活脑和肝中PI3K/AKT相关的HSP70反应，扰乱炎症反应并促进氧化损伤。用D -（-）-QA治疗可显著阻止氨水平升高并改善肝功能。此外，D -（-）-QA显著抑制了肝和脑组织中TNF-α和IL-1β等促炎细胞因子的增加以及MDA升高和SOD及GSH降低。通过抑制脑和肝组织中的HSP70以及PI3K/AKT信号传导，给予D -（-）-QA减轻了炎症和氧化损伤。D -（-）-QA可能通过抑制炎症和氧化损伤信号传导针对HE的发病机制成为当前临床干预的替代方法。
