School of Life Sciences and Biopharmaceutical Science, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China.
School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China.
Chem Biol Interact. 2021 Apr 1;338:109425. doi: 10.1016/j.cbi.2021.109425. Epub 2021 Feb 19.
Non-steroidal Anti-inflammatory Drugs (NSAIDs) are widely used because of their excellent anti-inflammatory and analgesic effects. However, NSAIDs could cause certain cardiac side effects, such as myocardial infarction, heart failure, atrial fibrillation, arrhythmia and sudden cardiac death. Therefore, meloxicam, nimesulide, piroxicam, and diclofenac were selected and the whole cell patch clamp technique was used to investigate the electrophysiological regulatory effects of them on the sodium channel hNav1.5 and potassium channel hKv11.1, which were closely associated to the biotoxicity of cardiac, and to explore the potential cardiac risk mechanism. The results showed that the four NSAIDs could inhibit the peak currents of hNav1.5 and hKv11.1. Furthermore, the four NSAIDs could affect both the activation and inactivation processes of hNav1.5 with I-V curves left-shifted to hyperpolarized direction in activation phase. These data indicate that the inhibition effects of Nav1.5 and Kv11.1 by meloxicam, nimesulide, piroxicam, and diclofenac might contribute to their potential cardiac risk. These findings provide a basis for the discovery of other potential cardiac risk targets for NSAIDs.
非甾体抗炎药（NSAIDs）因其出色的抗炎和镇痛效果而被广泛应用。然而，NSAIDs 可能会引起某些心脏副作用，如心肌梗死、心力衰竭、心房颤动、心律失常和心脏性猝死。因此，选择了美洛昔康、尼美舒利、吡罗昔康和双氯芬酸，并使用全细胞膜片钳技术研究它们对与心脏毒性密切相关的钠通道 hNav1.5 和钾通道 hKv11.1 的电生理调节作用，以探讨潜在的心脏风险机制。结果表明，这四种 NSAIDs 均可抑制 hNav1.5 和 hKv11.1 的峰值电流。此外，这四种 NSAIDs 均可影响 hNav1.5 的激活和失活过程，使 I-V 曲线在激活相向左移至超极化方向。这些数据表明，美洛昔康、尼美舒利、吡罗昔康和双氯芬酸对 Nav1.5 和 Kv11.1 的抑制作用可能是它们潜在的心脏风险的原因。这些发现为 NSAIDs 的其他潜在心脏风险靶标提供了依据。
