ABSTRACT

The circadian rhythm is constituted by genes/proteins, such as Cryptochrome (Cry). Medications including general anesthetics can alter these genes/proteins thus toxicity occurs. We claim that activation of Cry may contribute to the reduction of anesthetic-induced oxidative stress. In this study, the effect of combination therapy of Cry activator, KL001 with isoflurane was investigated. Twenty-four mice were divided into 4 groups as control, KL001, isoflurane, and KL001 plus isoflurane. The Cry levels and oxidative stress parameters including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were investigated. The results showed decreased MDA level in erythrocyte and liver and CAT activity in liver whereas increased GSH-Px activity in liver and brain and SOD activity in erythrocyte, kidney, and brain, in the isoflurane group. Isoflurane remarkably changed the oxidative stress parameters in the brain. Moreover, we found decreased Cry level in plasma, liver, and brain in the isoflurane group. KL001 decreased isoflurane-induced oxidative stress and increased Cry level inhibited by isoflurane. In conclusion, our data indicated that the potential oxidative stress of isoflurane can be reduced by triggering the Cry level with a synthetic activator. Further research is needed to establish the relationship between KL001 and drug-induced oxidative stress.

摘要

昼夜节律由基因/蛋白质构成，例如隐花色素 (Cry)。包括全身麻醉剂在内的药物可以改变这些基因/蛋白质，从而产生毒性。我们声称 Cry 的激活可能有助于减少麻醉剂引起的氧化应激。在本研究中，研究了 Cry 激活剂 KL001 与异氟醚联合治疗的效果。将24只小鼠分为4组作为对照，KL001、异氟醚和KL001加异氟醚。研究了 Cry 水平和氧化应激参数，包括丙二醛 (MDA)、超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT) 和谷胱甘肽过氧化物酶 (GSH-Px)。结果显示，红细胞和肝脏中的 MDA 水平降低，肝脏中的 CAT 活性降低，而肝脏和大脑中的 GSH-Px 活性和红细胞、肾脏、肾脏中的 SOD 活性增加。和大脑，在异氟醚组中。异氟醚显着改变了大脑中的氧化应激参数。此外，我们发现异氟醚组血浆、肝脏和大脑中的 Cry 水平降低。KL001 降低了异氟醚诱导的氧化应激并增加了异氟醚抑制的 Cry 水平。总之，我们的数据表明，通过使用合成激活剂触发 Cry 水平，可以降低异氟醚的潜在氧化应激。需要进一步的研究来确定 KL001 与药物诱导的氧化应激之间的关系。KL001 降低了异氟醚诱导的氧化应激并增加了异氟醚抑制的 Cry 水平。总之，我们的数据表明，通过使用合成激活剂触发 Cry 水平，可以降低异氟醚的潜在氧化应激。需要进一步的研究来确定 KL001 与药物诱导的氧化应激之间的关系。KL001 降低了异氟醚诱导的氧化应激并增加了异氟醚抑制的 Cry 水平。总之，我们的数据表明，通过使用合成激活剂触发 Cry 水平，可以降低异氟醚的潜在氧化应激。需要进一步的研究来确定 KL001 与药物诱导的氧化应激之间的关系。