Raish Mohammad, Ahmad Ajaz, Ahmad Ansari Mushtaq, Ahad Abdul, Al-Jenoobi Fahad I, Al-Mohizea Abdullah M, Khan Altaf, Ali Naushad
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Biomed Pharmacother. 2018 Dec;108:224-231. doi: 10.1016/j.biopha.2018.09.032. Epub 2018 Sep 13.
Pulmonary fibrosis is a multifaceted disease with high mortality and morbidity, and it is commonly nonresponsive to conventional therapy.
We explore the possible discourse of sinapic acid (SA) against the prevention of bleomycin (BLM)-instigated lung fibrosis in rats through modulation of Nrf2/HO-1 and NF-κB signaling pathways.
DESIGN/METHODS: Lung fibrosis was persuaded in Sprague-Dawley rats by a single intratracheal BLM (6.5 U/kg) injection. Then, these rats were treated with SA (10 and 20 mg/kg, p.o.) for 28 days. The normal control rats provided saline as a substitute of BLM. The lung function and biochemical, histopathological, and molecular alterations were studied in serum, bronchoalveolar lavage fluid (BALF), and the lungs tissues.
SA treatment significantly restored BLM-induced alterations in body weight index and serum biomarkers [lactate dehydrogenase (LDH) and alkaline phosphatase (ALP)]. SA (10 and 20 mg/kg) treatment appeared to show a pneumoprotective effect through upregulation of antioxidant status, downregulation of inflammatory cytokines and MMP-7 expression, and reduction of collagen accumulation (hydroxyproline). Nrf2, HO-1, and TGF-β expression was downregulated in BLM-induced fibrosis model, while the reduced expression levels were significantly and dose-dependently upregulated by SA (10 and 20 mg/kg) treatment. We demonstrated that SA ameliorates BLM-induced lung injuries through inhibition of apoptosis and induction of Nrf2/HO-1-mediated antioxidant enzymes via NF-κB inhibition. The histopathological findings also revealed that SA treatment (10 and 20 mg/kg) significantly ameliorated BLM-induced lung injury.
The present results showed the ability of SA to restore the antioxidant system and to inhibit oxidative stress, proinflammatory cytokines, extracellular matrix, and TGF-β. This is first report demonstrating that SA amoleriates BLM induced lung injuries through inhibition of apoptosis and induction of Nrf2 and HO-1 mediated antioxidant enzyme via NF-κB inhibition. The histopathological finding reveals that SA treatment (10 and 20 mg/kg) significantly ameliorates BLM induced lung injuries.
肺纤维化是一种多方面的疾病，死亡率和发病率高，通常对传统治疗无反应。
我们通过调节Nrf2/HO-1和NF-κB信号通路，探讨芥子酸（SA）预防博来霉素（BLM）诱导的大鼠肺纤维化的可能机制。
设计/方法：通过气管内单次注射BLM（6.5 U/kg）诱导Sprague-Dawley大鼠肺纤维化。然后，用SA（10和20 mg/kg，口服）治疗这些大鼠28天。正常对照大鼠给予生理盐水替代BLM。研究了血清、支气管肺泡灌洗液（BALF）和肺组织中的肺功能以及生化、组织病理学和分子改变。
SA治疗显著恢复了BLM诱导的体重指数和血清生物标志物[乳酸脱氢酶（LDH）和碱性磷酸酶（ALP）]的改变。SA（10和20 mg/kg）治疗似乎通过上调抗氧化状态、下调炎性细胞因子和MMP-7表达以及减少胶原蛋白积累（羟脯氨酸）显示出肺保护作用。在BLM诱导的纤维化模型中，Nrf2、HO-1和TGF-β表达下调，而SA（10和20 mg/kg）治疗显著且剂量依赖性地上调了降低的表达水平。我们证明SA通过抑制凋亡并通过抑制NF-κB诱导Nrf2/HO-1介导的抗氧化酶来改善BLM诱导的肺损伤。组织病理学结果还显示，SA治疗（$10和20 mg/kg）显著改善了BLM诱导的肺损伤。
目前的结果表明SA具有恢复抗氧化系统并抑制氧化应激、促炎细胞因子、细胞外基质和TGF-β的能力。这是首次报道表明SA通过抑制凋亡并通过抑制NF-κB诱导Nrf2和HO-1介导的抗氧化酶来改善BLM诱导的肺损伤。组织病理学结果显示，SA治疗（10和20 mg/kg）显著改善了BLM诱导的肺损伤。
