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Nicorandil mitigates amiodarone-induced pulmonary toxicity and fibrosis in association with the inhibition of lung TGF-β1/PI3K/Akt1-p/mTOR axis in rats
Clinical and Experimental Pharmacology and Physiology ( IF 2.4 ) Pub Date : 2022-10-08 , DOI: 10.1111/1440-1681.13728
Inas Harb 1 , Hend Ashour 2, 3 , Laila A Rashed 4 , Abeer Mostafa 4 , Mai Samir 4 , Basma Emad Aboulhoda 5 , Hala El-Hanbuli 6 , Eman Rashwan 7, 8 , Heba Mahmoud 1
Clinical and Experimental Pharmacology and Physiology ( IF 2.4 ) Pub Date : 2022-10-08 , DOI: 10.1111/1440-1681.13728
Inas Harb 1 , Hend Ashour 2, 3 , Laila A Rashed 4 , Abeer Mostafa 4 , Mai Samir 4 , Basma Emad Aboulhoda 5 , Hala El-Hanbuli 6 , Eman Rashwan 7, 8 , Heba Mahmoud 1
Affiliation
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The long-term side effect of the antiarrhythmic drug, amiodarone (AMIO), such as lung toxicity, remains a critical clinical issue. The previous knowledge denotes diverse antioxidant, anti-inflammatory, and antifibrotic properties of the anti-anginal drug, nicorandil (NI). Therefore, we aimed to investigate the possible protective effect of NI on pulmonary tissue remodelling following AMIO-induced lung toxicity. The included rats were assigned into four equal groups (n = 8): (1) control, (2) control group that received NI 10 mg kg−1 day−1, (3) model group that received AMIO in a dose of 60 mg kg−1 day−1, and (4) treated group (AMIO-NI) that were treated with AMIO plus NI as shown above. Drug administration continued for 10 weeks. AMIO resulted in deteriorated (p < 0.001) pulmonary functions accompanied by respiratory acidosis. AMIO showed an obvious histological injury score with intense collagen deposition, disturbed nitric oxide synthase enzymes (NOS/iNOS), and increased alpha smooth muscle actin expression. Furthermore, AMIO upregulated the transforming growth factor (TGF-β1)/phosphoinositide-3 kinase (PI3K)-Akt1-p/mammalian target of rapamycin (mTOR) axis, which determined the possible mechanism of AMIO on pulmonary remodelling. NI treatment significantly (p < 0.001) prevented the AMIO-induced lung toxicity, as well as inhibited the TGF-β1/PI3K/Akt1-p/mTOR axis in the lung tissue of rats. The results were confirmed by an in-vitro study.
中文翻译：
尼可地尔减轻胺碘酮诱导的肺毒性和纤维化与大鼠肺 TGF-β1/PI3K/Akt1-p/mTOR 轴的抑制有关
抗心律失常药物胺碘酮 (AMIO) 的长期副作用，如肺毒性，仍然是一个关键的临床问题。先前的知识表明抗心绞痛药物尼可地尔 (NI) 具有多种抗氧化、抗炎和抗纤维化特性。因此，我们旨在研究 NI 对 AMIO 诱导的肺毒性后肺组织重塑的可能保护作用。纳入的大鼠被分配到四个相等的组 ( n = 8)：(1) 对照组，(2) 接受 NI 10 mg kg -1 天-1的对照组，(3) 接受 AMIO 剂量为 60 的模型组mg kg −1 天−1和 (4) 治疗组 (AMIO-NI)，如上所示用 AMIO 加 NI 治疗。给药持续 10 周。AMIO 导致 ( p < 0.001) 肺功能恶化并伴有呼吸性酸中毒。AMIO 显示出明显的组织学损伤评分，伴有强烈的胶原蛋白沉积、一氧化氮合酶 (NOS/iNOS) 紊乱以及 α 平滑肌肌动蛋白表达增加。此外，AMIO 上调了转化生长因子 (TGF-β1)/磷酸肌醇-3 激酶 (PI3K)-Akt1-p/哺乳动物雷帕霉素靶点 (mTOR) 轴，这决定了 AMIO 对肺重塑的可能机制。NI 处理显着 ( p < 0.001) 防止 AMIO 引起的肺毒性，并抑制大鼠肺组织中的 TGF-β1/PI3K/Akt1-p/mTOR 轴。体外研究证实了这一结果。
更新日期：2022-10-08
中文翻译：
尼可地尔减轻胺碘酮诱导的肺毒性和纤维化与大鼠肺 TGF-β1/PI3K/Akt1-p/mTOR 轴的抑制有关
抗心律失常药物胺碘酮 (AMIO) 的长期副作用，如肺毒性，仍然是一个关键的临床问题。先前的知识表明抗心绞痛药物尼可地尔 (NI) 具有多种抗氧化、抗炎和抗纤维化特性。因此，我们旨在研究 NI 对 AMIO 诱导的肺毒性后肺组织重塑的可能保护作用。纳入的大鼠被分配到四个相等的组 ( n = 8)：(1) 对照组，(2) 接受 NI 10 mg kg -1 天-1的对照组，(3) 接受 AMIO 剂量为 60 的模型组mg kg −1 天−1和 (4) 治疗组 (AMIO-NI)，如上所示用 AMIO 加 NI 治疗。给药持续 10 周。AMIO 导致 ( p < 0.001) 肺功能恶化并伴有呼吸性酸中毒。AMIO 显示出明显的组织学损伤评分，伴有强烈的胶原蛋白沉积、一氧化氮合酶 (NOS/iNOS) 紊乱以及 α 平滑肌肌动蛋白表达增加。此外，AMIO 上调了转化生长因子 (TGF-β1)/磷酸肌醇-3 激酶 (PI3K)-Akt1-p/哺乳动物雷帕霉素靶点 (mTOR) 轴，这决定了 AMIO 对肺重塑的可能机制。NI 处理显着 ( p < 0.001) 防止 AMIO 引起的肺毒性，并抑制大鼠肺组织中的 TGF-β1/PI3K/Akt1-p/mTOR 轴。体外研究证实了这一结果。
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