伞形酮对对乙酰氨基酚诱导的小鼠肝脏氧化应激和炎症的改善作用。
Ameliorative effects of umbelliferone against acetaminophen-induced hepatic oxidative stress and inflammation in mice.
发表日期:2024 Feb
作者:
Saeed Sadeghinejad, Mehrnoosh Mousavi, Leila Zeidooni, Esrafil Mansouri, Shokooh Mohtadi, Mohammad Javad Khodayar
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
对乙酰氨基酚(APAP)是一种常用的解热镇痛药,过量服用会引起急性肝毒性。伞形酮 (UMB) 具有多种药理作用。本研究探讨UMB对APAP引起的急性肝毒性的保肝作用。将49只雄性小鼠分为7组。对照组接受媒介物(腹腔注射),UMB 组接受 UMB(120 mg/kg,腹腔注射),APAP 组接受单剂量 APAP(350 mg/kg,腹腔注射)治疗,预处理组接受 N-乙酰半胱氨酸(NAC, APAP 前分别给予 200 mg/kg(腹腔注射)或不同剂量的 UMB(30、60 和 120 mg/kg,腹腔注射)。 APAP注射后24小时,处死小鼠并收集血液和肝脏样本。然后,对血清和组织样本进行生化和组织学研究。单剂量的APAP引起血清肝酶升高,包括丙氨酸转氨酶、天冬氨酸转氨酶和碱性磷酸酶。小鼠肝组织中硫代巴比妥酸反应物质、肿瘤坏死因子-α和一氧化氮的含量增加。此外,APAP组的总硫醇含量和抗氧化酶(过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶)的活性显着降低。组织学结果证实了APAP诱导的肝毒性。然而,UMB(60 和 120 mg/kg 更有效)可减轻 APAP 引起的肝损伤,这与 NAC 的效果相当。这项研究的结果提供了证据,证明 UMB 通过其抗氧化和抗炎作用改善 APAP 引起的肝损伤效果。版权所有:© 2024 Research in Pharmaceutical Sciences。
Acetaminophen (APAP) is a commonly used antipyretic and pain reliever that its overdose causes acute liver toxicity. Umbelliferone (UMB) has many pharmacological effects. In this study, the hepatoprotective effect of UMB on acute hepatotoxicity induced by APAP was investigated.Forty-nine male mice were separated into seven groups. The control received vehicle (i.p.), UMB group received UMB (120 mg/kg, i.p.), APAP group was treated with a single dose of APAP (350 mg/kg, i.p.), and pretreated groups received N-acetylcysteine (NAC, 200 mg/kg, i.p.) or different doses of UMB (30, 60, and 120 mg/kg, i.p.), respectively before APAP. Twenty-four hours after APAP injection, mice were sacrificed and blood and liver samples were collected. Then, serum and tissue samples were investigated for biochemical and histological studies.A single dose of APAP caused elevation in the serum liver enzymes, including alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. The amounts of thiobarbituric acid reactive substances, tumor necrosis factor-alpha, and nitric oxide increased in the mice's liver tissue. Moreover, the amount of total thiol and the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) significantly diminished in the APAP group. Histological results confirmed the hepatotoxicity induced by APAP. However, UMB (more effective at 60 and 120 mg/kg) lessened APAP-induced hepatic injuries, which is comparable with NAC effects.The findings of this study provided evidence that UMB ameliorates liver injury induced by APAP through its antioxidant and anti-inflammatory effects.Copyright: © 2024 Research in Pharmaceutical Sciences.