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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.

Toxicological evaluation of the interaction between circadian rhythm activator; KL001 and general anesthetic; isoflurane