表儿茶素对对乙酰氨基酚诱发的小鼠肝损伤的预防和治疗作用

IF 1 Q4 PHARMACOLOGY & PHARMACY Jundishapur Journal of Natural Pharmaceutical Products Pub Date : 2023-11-28 DOI:10.5812/jjnpp-137505
F. Dehbashi, L. Zeidooni, Esrafil Mansouri, Elaheh Mohammadi, M. Khodayar
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摘要

背景:如今,使用对乙酰氨基酚(APAP)等非处方药可能会导致严重的肝损伤,不仅在大剂量时会发生,在治疗剂量时也会因营养缺乏、酗酒或使用细胞色素 p450 诱导剂而发生。研究目的本研究评估了表儿茶素(EPC)对 APAP 引起的肝毒性的保护作用,以寻找一种有效且廉价的治疗方法。方法:将动物分为预防性和治疗性两组:将动物分为预防组和治疗组。在预防研究中,动物连续五天服用 EPC(25、50 和 100 毫克/千克/天),最后一次剂量在 APAP(400 毫克/千克)前 1 小时服用。在治疗组,动物在注射 APAP 之前和之后 2 小时服用 EPC。所有动物均被处死,并采集血液和肝脏样本进行进一步分析。对肝脏病理学、酶、氧化剂、抗氧化剂、炎症和抗炎因子进行了评估。结果EPC 能明显降低 APAP 治疗小鼠肝脏生物标志物 ALT 和 AST 的血清活性水平。此外,EPC 还明显降低了肝脏中硫代巴比妥酸反应物质的水平,并显著提高了总硫醇和过氧化氢酶活性的水平。组织病理学结果与生化评估结果非常一致。最有效的剂量为 EPC 100 毫克/千克,治疗组的效果优于预防组。结论EPC通过抑制氧化应激减轻了小鼠肝脏的毒性,可被视为一种预防和治疗药物,用于抑制和解决APAP引起的肝损伤。
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Preventive and Therapeutic Effects of Epicatechin on Acetaminophen-Induced Liver Injury in Mice
Background: Nowadays, the use of over-the-counter drugs such as acetaminophen (APAP) may cause severe liver injury, which can occur not only in high doses but also in therapeutic doses due to nutritional deficiency, alcoholism, or using cytochrome p450 inducers. Objectives: In this study, the protective effect of epicatechin (EPC) was evaluated against APAP-induced hepatotoxicity to find an effective and inexpensive therapy. Methods: The animals were divided into preventive and therapeutic groups. In the preventive study, the animals received EPC (25, 50, and 100 mg/kg/day) for five days, and the last dose was administered 1 hour before APAP (400 mg/kg). In the therapeutic groups, the animals received EPC just before and 2 hours after the APAP injection. All the animals were killed, and blood and liver samples were taken for further analysis. The liver pathology, enzymes, and oxidant, antioxidant, inflammatory, and anti-inflammatory factors were evaluated. Results: EPC significantly decreased the serum activity level of the liver biomarkers ALT and AST in the APAP-treated mice. Furthermore, the hepatic levels of thiobarbituric acid-reactive substances were noticeably lowered, and the levels of total thiol and catalase activity increased significantly with EPC. Histopathological results were strongly consistent with those of the biochemical estimations. The most effective dose was observed at EPC 100 mg/kg, and the therapeutic groups showed better results than the preventive groups. Conclusions: EPC attenuated the liver toxicity in the mice by suppressing oxidative stress and can be considered a preventive and therapeutic agent for inhibiting and resolving the liver damage induced by APAP.
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