Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Environ Toxicol. 2021 Jul;36(7):1261-1268. doi: 10.1002/tox.23123. Epub 2021 Mar 15.
The present research has been investigated to study the protective outcomes of sinapic acid (SA) against methotrexate (MTX) encouraged liver damage in rats by modulating the Nrf2/HO-1 and NF-κB signaling pathways. The animals were arbitrarily allocated into four groups: group I rats administered a 0.5% carboxymethyl cellulose (CMC) vehicle orally for 15 consecutive days with a single intravenous standard saline injection (0.9% NaCl) on day seven. Groups II, III, and IV were injected intraperitoneally with 20 mg MTX/kg on 7th day. Animals in group III and IV were treated orally for 14 days with 20 mg of SA/kg dissolved daily in 0.5% CMC respectively. In all experimental groups, liver function, biochemical, histopathological and molecular changes were evaluated. MTX-induced changes in liver function indices like ALT, AST, and ALP are substantially restored with SA pretreatment. Moreover, antioxidant defense mechanisms (GSH, SOD, and CAT) and oxidative/nitrostative stress (MDA and NO) and inflammatory cytokine (TNF-α, IL-β and MPO) were also substantially restored. Furthermore, the conclusions indicate that SA prevents the hepatic damage caused by MTX through apoptosis inhibition and stimulation of Nrf2/HO-1-medial antioxidant enzymes by NF-κB inhibition. Histological findings have shown that SA therapy has greatly protected liver damage caused by MTX.
本研究旨在通过调节 Nrf2/HO-1 和 NF-κB 信号通路，研究芥子酸（SA）对甲氨蝶呤（MTX）诱导的大鼠肝损伤的保护作用。将动物随机分为四组：第 I 组大鼠连续 15 天每天口服 0.5%羧甲基纤维素（CMC）载体，第 7 天给予单次静脉标准生理盐水（0.9%NaCl）注射。第 II、III 和 IV 组在第 7 天腹腔内注射 20mg MTX/kg。第 III 和 IV 组大鼠分别每天口服 20mg/kg 的 SA，溶于 0.5%CMC 中，连续治疗 14 天。在所有实验组中，评估了肝功能、生化、组织病理学和分子变化。SA 预处理可显著恢复 MTX 诱导的肝功能指标 ALT、AST 和 ALP 的变化。此外，抗氧化防御机制（GSH、SOD 和 CAT）和氧化/硝化应激（MDA 和 NO）以及炎症细胞因子（TNF-α、IL-β 和 MPO）也得到了显著恢复。此外，研究结果表明，SA 通过抑制 NF-κB 抑制凋亡和刺激 Nrf2/HO-1-介导的抗氧化酶来防止 MTX 引起的肝损伤。组织学发现表明，SA 治疗极大地保护了 MTX 引起的肝损伤。
