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.

中文翻译：

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芥子酸通过调节 Nrf-2/HO-1 信号传导减轻甲氨蝶呤诱导的大鼠肝损伤

本研究旨在通过调节 Nrf2/HO-1 和 NF-κB 信号通路来研究芥子酸 (SA) 对甲氨蝶呤 (MTX) 的保护作用，促进大鼠肝损伤。动物被任意分为四组：第 I 组大鼠连续 15 天口服施用 0.5% 羧甲基纤维素 (CMC) 载体，并在第 7 天单次静脉注射标准盐水 (0.9% NaCl)。第 II、III 和 IV 组在第 7 天腹膜内注射 20mg MTX/kg。组 III 和 IV 中的动物分别用每天溶解在 0.5% CMC 中的 20 mg SA/kg 口服治疗 14 天。在所有实验组中，评估肝功能、生化、组织病理学和分子变化。MTX 引起的肝功能指标如 ALT、AST、SA 预处理后 ALP 基本恢复。此外，抗氧化防御机制（GSH、SOD 和 CAT）和氧化/亚硝化应激（MDA 和 NO）和炎性细胞因子（TNF-α、IL-β 和 MPO）也得到显着恢复。此外，结论表明，SA 通过抑制细胞凋亡和通过 NF-κB 抑制刺激 Nrf2/HO-1-中抗氧化酶来预防 MTX 引起的肝损伤。组织学发现表明，SA疗法极大地保护了MTX引起的肝损伤。结论表明SA通过抑制细胞凋亡和通过NF-κB抑制刺激Nrf2/HO-1-中抗氧化酶来预防MTX引起的肝损伤。组织学发现表明，SA疗法极大地保护了MTX引起的肝损伤。结论表明SA通过抑制细胞凋亡和通过NF-κB抑制刺激Nrf2/HO-1-中抗氧化酶来预防MTX引起的肝损伤。组织学发现表明，SA疗法极大地保护了MTX引起的肝损伤。