Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Laboratory Medicine, The Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China.
Pharm Biol. 2022 Dec;60(1):1915-1924. doi: 10.1080/13880209.2022.2123941.
Sevoflurane (Sev) is a commonly used surgical anaesthetic; it has neurotoxic effects on the brain. Echinatin (Ech) is reported to have anti-inflammatory and antioxidant activity.
This research confirms the effect of Ech on Sev-induced neurotoxicity and cognitive deficits.
Primary rat hippocampal neurons were treated with 4.1% Sev for 6 h in the presence of Ech (5, 10, and 20 μM) or vehicle, followed by a further 42 h of culture. Male Sprague-Dawley aged rats were divided into 6 groups ( = 6): control, Sev, Sev + Ech (20 mg/kg;), Sev + Ech (40 mg/kg), and Sev + Ech (80 mg/kg). Rats were intraperitoneally injected with Ech or vehicle 1 h before Sev exposure (2% Sev for 5 h).
We found that Ech (5, 10, and 20 μM) elevated cell viability (1.29-, 1.51-, 1.68-fold) but mitigated apoptosis (23.87% vs. 16.48%, 12.72%, 9.02%), oxidative stress, and ferroptosis in hippocampal neurons with Sev treatment. Ech activated the Nrf2 expression in Sev-induced and models of anaesthetic neurotoxicity. Ech also weakened neurotoxicity in hippocampal neurons with Sev treatment by increasing Nrf2 expression level. Moreover, Ech alleviated hippocampus neurons apoptosis (19.38% vs. 16.05%, 11.71%, 8.88%), oxidative stress, and ferroptosis in rats with Sev treatment. Ech improved Sev-induced cognitive deficits in rats.
Ech alleviates Sev-induced neurotoxicity and cognitive deficits by mitigation of ferroptosis and oxidative stress. Ech may be developed as a new promising therapeutic drug for treatment of cerebral nerve injury caused by surgical anaesthesia.
七氟醚（Sev）是一种常用的手术麻醉剂；它对大脑有神经毒性作用。小驳骨（Ech）据报道具有抗炎和抗氧化活性。
本研究证实 Ech 对 Sev 诱导的神经毒性和认知缺陷的影响。
原代大鼠海马神经元在 4.1% Sev 存在下处理 6 小时，并用 Ech（5、10 和 20 μM）或载体处理，然后再培养 42 小时。雄性 Sprague-Dawley 大鼠分为 6 组（n=6）：对照组、Sev 组、Sev+Ech（20mg/kg）组、Sev+Ech（40mg/kg）组和 Sev+Ech（80mg/kg）组。大鼠在 Sev 暴露前 1 小时（2% Sev 5 小时）腹腔注射 Ech 或载体。
我们发现 Ech（5、10 和 20 μM）提高了细胞活力（1.29-、1.51-和 1.68-倍），但减轻了 Sev 处理的海马神经元中的凋亡（23.87%对 16.48%、12.72%和 9.02%）、氧化应激和铁死亡。Ech 激活了 Sev 诱导的麻醉神经毒性和 模型中的 Nrf2 表达。Ech 还通过增加 Nrf2 表达水平减弱了 Sev 处理的海马神经元的神经毒性。此外，Ech 减轻了 Sev 处理大鼠海马神经元凋亡（19.38%对 16.05%、11.71%和 8.88%）、氧化应激和铁死亡。Ech 改善了 Sev 诱导的大鼠认知缺陷。
Ech 通过减轻铁死亡和氧化应激缓解 Sev 诱导的神经毒性和认知缺陷。Ech 可能被开发为治疗手术麻醉引起的脑神经损伤的一种有前途的新型治疗药物。
