Telafarlı Mehmet Ali, Bora Ejder Saylav, Topal Firdes, Erbaş Oytun
Department of Emergency Medicine, Erzurum City Hospital, 25240 Erzurum, Turkey.
Department of Emergency Medicine, Faculty of Medicine, Izmir Katip Çelebi University, 35360 Izmir, Turkey.
Curr Issues Mol Biol. 2025 Jul 8;47(7):524. doi: 10.3390/cimb47070524.
Oxidative stress, mitochondrial dysfunction, and inflammatory responses cause acute liver failure in most cases of acetaminophen (APAP) overdose. Tamarixetin (Trx), an antioxidant and anti-inflammatory flavonoid, has not yet been studied in models of APAP-induced hepatotoxicity. Trx was tested for its protective effects on APAP-induced liver injury in rats using biochemical, histopathological, and oxidative stress parameters. Three groups of 30 male Wistar rats were randomly assigned to the following groups: control, APAP + Saline, and APAP + Trx (3 mg/kg/day, intraperitoneally for 3 days). A single 300 mg/kg intraperitoneal APAP dose caused hepatotoxicity. ALT, MDA, GSH, HSP-70, and thioredoxin were measured in blood and liver tissues. Liver sections were histopathologically examined. APAP depleted hepatic GSH and Trx and increased serum ALT and MDA. Trx treatment significantly reduced ALT (201.2 → 105.1 U/L), MDA (5.5 → 3.4 nmol/mg), and the percentage of histologically damaged hepatocytes (58.5% → 9.5%), while restoring GSH and thioredoxin levels. Notably, HSP-70 expression exceeded that of APAP and control levels, suggesting the modulation of the stress response. The Trx group showed significant hepatoprotection histologically. Trx reduces APAP-induced hepatic damage, likely through antioxidant and anti-inflammatory mechanisms. These findings suggest that Trx may be a natural hepatoprotectant, warranting clinical trials.
在大多数对乙酰氨基酚(APAP)过量服用的病例中,氧化应激、线粒体功能障碍和炎症反应会导致急性肝衰竭。柳穿鱼黄素(Trx)是一种抗氧化和抗炎类黄酮,尚未在APAP诱导的肝毒性模型中进行研究。本研究利用生化、组织病理学和氧化应激参数,测试了Trx对APAP诱导的大鼠肝损伤的保护作用。将三组30只雄性Wistar大鼠随机分为以下几组:对照组、APAP+生理盐水组和APAP+Trx组(3mg/kg/天,腹腔注射3天)。腹腔注射单次剂量300mg/kg的APAP会导致肝毒性。检测血液和肝组织中的谷丙转氨酶(ALT)、丙二醛(MDA)、谷胱甘肽(GSH)、热休克蛋白70(HSP-70)和硫氧还蛋白。对肝组织切片进行组织病理学检查。APAP使肝脏GSH和Trx减少,血清ALT和MDA升高。Trx治疗显著降低了ALT(201.2→105.1U/L)、MDA(5.5→3.4nmol/mg)以及组织学上受损肝细胞的百分比(58.5%→9.5%),同时恢复了GSH和硫氧还蛋白水平。值得注意的是,HSP-70的表达超过了APAP组和对照组的水平,表明应激反应得到了调节。Trx组在组织学上显示出显著的肝保护作用。Trx可能通过抗氧化和抗炎机制减轻APAP诱导的肝损伤。这些发现表明,Trx可能是一种天然的肝保护剂,值得进行临床试验。